RESUMEN

Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease that leads to dyspnea and progressive loss of lung function. This study aimed to investigate the protective effect of betanin (BET), the major pigment in red beetroot, on pulmonary fibrosis induced by bleomycin (BLM) in rats and to assess the underlying mechanisms. In this view, total and differential cell counts and LDH activity in bronchoalveolar lavage fluid were estimated. Furthermore, MDA and GSH contents in the lungs were colorimetrically measured, while hydroxyproline, NLRP3, ASC, caspase-1, TGF-ß1, and vimentin levels in lung tissue were evaluated using the ELISA technique. Moreover, IL-1ß, E-cadherin, and α-SMA expressions were analyzed by immunostaining of lung specimens. BET treatment protects against pulmonary fibrosis as indicated by the reduction in total and differential cell counts, LDH activity, hydroxyproline, NLRP3, ASC, caspase-1, IL-1ß, and TGF-ß1 levels. MDA content was also decreased following BET administration, while GSH content was elevated. Additionally, BET suppressed the EMT process as evidenced by an increase in E-cadherin expression besides the reduction in vimentin and α-SMA expressions. To conclude, these results revealed the protective effect of BET against pulmonary fibrosis that might be attributed to the attenuation of the NLRP3/IL-1ß/TGF-ß1 signaling pathway and EMT process.

Asunto(s)

Fibrosis Pulmonar , Ratas , Animales , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Vimentina/genética , Vimentina/metabolismo , Bleomicina/toxicidad , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Betacianinas/farmacología , Hidroxiprolina/efectos adversos , Hidroxiprolina/metabolismo , Pulmón , Cadherinas/metabolismo , Caspasas/metabolismo , Transición Epitelial-Mesenquimal

RESUMEN

The objective of this study was to investigate the effect of low-molecular-weight fish collagen (valine-glycine-proline-hydroxyproline-glycine-proline-alanine-glycine; LMWCP) on H2O2- or LPS-treated primary chondrocytes and monoiodoacetate (MIA)-induced osteoarthritis rat models. Our findings indicated that LMWCP treatment exhibited protective effects by preventing chondrocyte death and reducing matrix degradation in both H2O2-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. This was achieved by increasing the levels of aggrecan, collagen type I, collagen type II, TIMP-1, and TIMP-3, while simultaneously decreasing catabolic factors such as phosphorylation of Smad, MMP-3, and MMP-13. Additionally, LMWCP treatment effectively suppressed the activation of inflammation and apoptosis pathways in both LPS-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. These results suggest that LMWCP supplementation ameliorates the progression of osteoarthritis through its direct impact on inflammation and apoptosis in chondrocytes.

Asunto(s)

Cartílago Articular , Osteoartritis , Ratas , Animales , Condrocitos , Hidroxiprolina/efectos adversos , Hidroxiprolina/metabolismo , Glicina/farmacología , Peróxido de Hidrógeno/farmacología , Lipopolisacáridos/farmacología , Osteoartritis/inducido químicamente , Osteoartritis/tratamiento farmacológico , Osteoartritis/prevención & control , Inflamación/metabolismo , Colágeno Tipo II/farmacología , Péptidos/farmacología , Valina/efectos adversos , Valina/metabolismo , Células Cultivadas

RESUMEN

INTRODUCTION: The incidence of non-alcoholic fatty liver disease (NAFLD) has increased in recent years. Hepatic fibrosis (HF) is an important step in the progression of NAFLD to cirrhosis and even carcinoma and is also recognized as a possible reversal phase. AIMS: We previously found that the aqueous extract of Sedum Lineare Thunb. has hepatoprotective effects. This study investigated the hepatoprotective effect and mechanism of the Sedum Lineare Thunb. n-butanol phase (SLNP) on HF in rats. METHODS: Animals were intraperitoneally injected with thioacetamide solution twice a week for 8 weeks to prepare an HF model and were administered the corresponding drugs or an equal volume of normal saline by intragastric administration once a day for 8 weeks. Liver function, hydroxyproline and malondialdehyde (MDA) content, superoxide dismutase (SOD), Na+-K+-ATPase, and Ca2+-Mg2+-ATPase were analyzed using colorimetric methods. Moreover, mRNA expression and protein levels in the liver tissue were detected via quantitative polymerase chain reaction and western blotting, respectively. RESULTS: The results showed that SLNP could effectively improve the liver function of rats with HF and significantly reduce the content of hydroxyproline; the mRNA expression and protein levels of alpha-smooth muscle actin (α-SMA), collagen I, III, and IV, transforming growth factor beta 1 (TGF-ß1), Smad2/3, and Smad4 were also significantly reduced. Simultaneously, SLNP significantly increased the activities of SOD, Na+-K+- ATPase, and Ca2+-Mg2+-ATPase in the rat liver tissues, whereas it reduced the levels of MDA and SOD in the serum and liver tissues. CONCLUSION: This study revealed that SLNP elicits an anti-fibrotic effect by inhibiting oxidative stress and stellate cell activation, thereby reducing the formation and deposition of the extracellular matrix. The TGF-ß1/Smads signaling pathway may be involved in this process.

Asunto(s)

Enfermedad del Hígado Graso no Alcohólico , Factor de Crecimiento Transformador beta1 , Ratas , Animales , Factor de Crecimiento Transformador beta1/metabolismo , Tioacetamida/toxicidad , Tioacetamida/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Hidroxiprolina/efectos adversos , Hidroxiprolina/metabolismo , Transducción de Señal , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Hígado , Superóxido Dismutasa/efectos adversos , Superóxido Dismutasa/metabolismo , ARN Mensajero/metabolismo , Adenosina Trifosfatasas/efectos adversos , Adenosina Trifosfatasas/metabolismo

RESUMEN

Ulcerative colitis is a type of inflammatory bowel disease responsible for the inflammation of the innermost lining of the colon and rectum. The present study's objective is to determine the potential synergistic impact of quercetin (QR) and lycopene (LP) in ulcerative colitis (UC) induced in rats by ochratoxin A (OTA) by biochemical and morphological alterations. QR and LP were administered alone and in combination with the OTA for 7 days. OTA administration caused UC generation, resulting in significant changes in body weight percentage, disease activity index (DAI), macroscopic evaluation, colon weight/length ratio, and histological score. In addition to the above parameters, it also leads to elevated oxidative stress, i.e. increased malondialdehyde (MDA), nitric oxide (NO), myeloperoxidase (MPO), and hydroxyproline levels and decreased superoxide dismutase (SOD) and reduced glutathione (GSH) levels. Histological changes in the colon architecture were also observed suggestive of extensive mucosal damage. In addition, a high level of matrix metalloproteinase 7 (MMP7) was observed in immunohistochemistry, and a high level of gene expression of osteopontin (OPN), runt-related transcription factor 2 (RUNX2), MMP-7, and interleukin-6 (IL-6) was observed in OTA administered animals. The combination of QR and LP significantly restored the per cent body weight loss and DAI score and improved macroscopic and histological changes, colon weight/length ratio, and macroscopic damages. It also improved the biochemical parameters to near-normal levels, i.e. reduced MDA, NO, MPO, and hydroxyproline levels and increased SOD and GSH levels. In addition, OPN, Runx2, MMP-7, and IL-6 gene expression decreased compared to the OTA-induced UC group. Outcomes of the present study indicate the potential of QR + LP as anti-inflammatory and immunomodulatory agents against OTA-induced UC in rats.

Asunto(s)

Colitis Ulcerosa , Ratas , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Licopeno/farmacología , Licopeno/metabolismo , Quercetina/farmacología , Quercetina/uso terapéutico , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/farmacología , Metaloproteinasa 7 de la Matriz/metabolismo , Metaloproteinasa 7 de la Matriz/farmacología , Interleucina-6/genética , Interleucina-6/metabolismo , Hidroxiprolina/efectos adversos , Hidroxiprolina/metabolismo , Colon/metabolismo , Colon/patología , Superóxido Dismutasa/metabolismo

RESUMEN

it was aimed to discuss the effect of moxibustion (Mox) combined with Bu Fei Qu Yu (BFQY) decoction under the nuclear factor-κB (NF-κB)/transforming growth factor-ß1 (TGF-ß1)/Smads signaling pathway in the treatment of pulmonary fibrosis (PF). The PF rat models were prepared with bleomycin (BLM). They were divided into the normal (Nor) group, the PF model group (BLM puncture perfusion), the Mox group (grain-sized Mox at the back-shu points and Xuxiao points), the BFQY group (intragastrical BFQY decoction), and the Mox combined with BFQY decoction (Mox+BFQY) group. Lung tissue sections were prepared, and the hematoxylin-eosin (HE) staining and Masson staining were performed to observe the inflammatory response and the degree of PF. The contents of hydroxyproline (HYP), glutathione (GSH), and malondialdehyde (MDA), and the expressions of NF-κB p65, TGF-ß1, Smad2, and Smad7 in lung tissues were detected. Compared with those in the Nor group, the inflammatory response score, PF degree score, HYP, GSH, and MDA contents, NF-κB p65, TGF-ß1, and Smad2 expressions were significantly increased in the PF group, but Smad7 expression decreased (P<0.05). The above symptoms were significantly improved in the Mox, BFQY, and Mox+ BFQY groups (P<0.05). The effect was more remarkable in the Mox+BFQY group, and there was no significant difference in each index compared with those in the Nor group (P>0.05). Thus, the combined therapy of Mox and decoction had an effect on PF through the NF-κB/TGF-ß1/Smads pathway.

Asunto(s)

Moxibustión , Fibrosis Pulmonar , Animales , Bleomicina/toxicidad , Eosina Amarillenta-(YS)/efectos adversos , Glutatión , Hematoxilina/farmacología , Hidroxiprolina/efectos adversos , Hidroxiprolina/metabolismo , Malondialdehído , FN-kappa B/metabolismo , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/terapia , Ratas , Transducción de Señal , Factor de Crecimiento Transformador beta1/metabolismo

RESUMEN

Oxaceprol, a derivative of l-proline, is an established drug for managing osteoarthritis (OA) with better safety profile than non-steroidal anti-inflammatory drugs (NSAIDs). This systematic review and meta-analysis, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, evaluated the efficacy, safety and tolerability of oxaceprol in OA. Electronic databases for published and grey (unpublished) literature were searched to identify parallel-group randomized controlled trials (RCTs) evaluating the impact of oxaceprol in patients with OA. Risk of bias was assessed using the Cochrane collaboration's tool. A total of seven parallel-group RCTs involving 1087 participants were included in the systematic review. Meta-analysis, in Review Manager, demonstrated numerically greater/significant improvements compared to active control [diclofenac/ibuprofen]/placebo in pain and function of joint; similar improvement vs. active control in global treatment efficacy; no difference/significant difference vs. active control/placebo in NSAIDs as rescue medication. Treatment with oxaceprol showed numerically less adverse events (AEs) than active control (diclofenac: risk ratio [RR], 0.71; 95% confidence interval [CI], 0.45 to 1.11; p=0.14: ibuprofen: RR, 0.73; 95% CI, 0.30 to 1.78; p=0.49) and significantly fewer AEs compared to placebo (RR, 0.76; 95% CI, 0.63 to 0.92; p=0.004). Given the nature of small-to-moderate sample size and short duration of eligible studies, the available clinical evidence of oxaceprol in the management of OA is modest - though looks promising. New and better RCTs with larger sample size and longer follow-up are warranted to strengthen the use of oxaceprol in clinical setting for managing OA.

Asunto(s)

Antirreumáticos/uso terapéutico , Hidroxiprolina/uso terapéutico , Osteoartritis/tratamiento farmacológico , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Antirreumáticos/efectos adversos , Diclofenaco/administración & dosificación , Diclofenaco/efectos adversos , Humanos , Hidroxiprolina/efectos adversos , Ibuprofeno/administración & dosificación , Ibuprofeno/efectos adversos , Osteoartritis/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Tamaño de la Muestra

RESUMEN

The duration and dose-dependent side effects of conventional intra-articular corticosteroid treatment in osteoarthritis (OA) like cartilage damage and chondrocyte toxicity warrant the search for alternative therapeutics. Oxaceprol, a recognized oral therapeutic agent for osteoarthritis, is yet to be explored for its intra-articular route of administration confirming better safety profile. In this study, a comparative evaluation of intra-articular oxaceprol and corticosteroid is carried out in osteoarthritis rabbit model. Osteoarthritis was induced by monosodium iodoacetate in rabbits. After randomization into three groups of five animals each: OA with intra-articular injection of saline, OA with intra-articular injection of oxaceprol, and OA with intra-articular injection of corticosteroids, treatment efficacy was analyzed by evaluation of inflammation through knee swelling, pain assessment by wire walking, and hot plate method. Further biopsies were collected for histological characterization. Intra-articular oxaceprol and corticosteroids reduced 20.5 and 24.5% knee swelling respectively within 4 weeks compared to those in control osteoarthritic rabbits. Oxaceprol exhibited analgesic action in visual analogue scoring of wire walking method. Hot plate test further confirmed drastic minimization of pain in oxaceprol intervention. Histological investigation suggested that application of oxaceprol has the abilities to protect articular cartilages from degenerative changes that occur in osteoarthritis. Marked improvement both in bone and cellular matrixes was observed in oxaceprol-treated group while gross lesions were visible and consisted of a well-demarcated area of cartilage erosion in control group. Intra-articular injection of oxaceprol showed remarkable improvement of articular cartilage in chemically induced osteoarthritic rabbits.

Asunto(s)

Antirreumáticos/administración & dosificación , Hidroxiprolina/administración & dosificación , Osteoartritis de la Rodilla/tratamiento farmacológico , Animales , Antirreumáticos/efectos adversos , Artralgia/diagnóstico , Artralgia/tratamiento farmacológico , Cartílago Articular , Modelos Animales de Enfermedad , Hidroxiprolina/efectos adversos , Inyecciones Intraarticulares , Articulación de la Rodilla/patología , Masculino , Osteoartritis de la Rodilla/patología , Dimensión del Dolor , Conejos , Distribución Aleatoria , Equivalencia Terapéutica

RESUMEN

OBJECTIVES: To assess efficacy and safety of oxaceprol, a hydroxyproline derivative with putative mechanism of action different from traditional nonsteroidal anti-inflammatory drugs, in symptomatic knee osteoarthritis, in comparison to tramadol. MATERIALS AND METHODS: A parallel group, double-blind, randomized controlled trial was conducted with ambulatory patients over 50 years age suffering from knee osteoarthritis causing pain of at least moderate intensity. Patients were randomized to receive either oxaceprol 200 mg thrice daily or tramadol 50 mg thrice daily for 12 weeks. The primary efficacy variable was symptom relief as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) version 3.1 for pain, stiffness, and physical function. Responder rate (50% pain relief), patient's Clinical Global Impression (CGI), and rescue medication use were other outcomes measured. Vital signs, routine blood counts, tests of hepatorenal function and treatment-emergent adverse events were recorded for safety assessment. RESULTS: From 91 patients recruited, 43 on oxaceprol and 36 on tramadol were evaluable. The WOMAC scores declined significantly from baseline in each arm but remained comparable between groups throughout the 12-week study period. The CGI ratings and 50% responder rates were also comparable at the final visit. Differences in dose up-titration and rescue medication requirements were statistically nonsignificant. So also were the adverse event counts. Compliance was satisfactory in both groups. CONCLUSIONS: Efficacy and tolerability of oxaceprol were comparable to tramadol, and the drug can be considered as an alternative to low-potency opioids in the management of knee osteoarthritis.

Asunto(s)

Hidroxiprolina/uso terapéutico , Osteoartritis de la Rodilla/tratamiento farmacológico , Dolor/tratamiento farmacológico , Tramadol/uso terapéutico , Anciano , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Hidroxiprolina/efectos adversos , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/complicaciones , Dolor/etiología , Dimensión del Dolor , Tramadol/efectos adversos

RESUMEN

OBJECTIVES: Polymorphism of the gene for matrix GLA protein (MGP), a calcification inhibitor, is associated with nephrolithiasis. However, experimental investigations of MGP role in stone pathogenesis are limited. We determined the effect of renal epithelial exposure to oxalate (Ox), calcium oxalate (CaOx) monohydrate (COM) or hydroxyapatite (HA) crystal on the expression of MGP. METHODS: MDCK cells in culture were exposed to 0.3, 0.5 or 1 mM Ox and 33, 66 or 133-150 µg/cm(2) of COM/HA for 3-72 h. MGP expression and production were determined by Western blotting and densitometric analysis. Enzyme-linked immunosorbent assay was performed to determine MGP release into the medium. Hyperoxaluria was induced in male Sprague-Dawley rats by feeding hydroxyl-L-proline. Immunohistochemistry was performed to detect renal MGP expression. RESULTS: Exposure to Ox and crystals led to time- and concentration-dependent increase in expression of MGP in MDCK cells. Cellular response was quicker to crystal exposure than to the Ox, expression being significantly higher after 3-h exposure to COM or HA crystals and more than 6 h of exposure to Ox. MGP expression was increased in kidneys of hyperoxaluric rats particularly in renal peritubular vessels. CONCLUSION: We demonstrate increased expression of MGP in renal tubular epithelial cells exposed to Ox or CaOx crystals as well as the HA crystals. The most significant finding of this study is the increased staining seen in renal peritubular vessels of the hyperoxaluric rats, indicating involvement of renal endothelial cells in the synthesis of MGP.

Asunto(s)

Oxalato de Calcio/efectos adversos , Proteínas de Unión al Calcio/metabolismo , Células Epiteliales/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Riñón/metabolismo , Nefrolitiasis/inducido químicamente , Nefrolitiasis/metabolismo , Animales , Oxalato de Calcio/farmacología , Células Cultivadas , Modelos Animales de Enfermedad , Perros , Relación Dosis-Respuesta a Droga , Durapatita/efectos adversos , Durapatita/farmacología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Hidroxiprolina/efectos adversos , Hiperoxaluria/inducido químicamente , Hiperoxaluria/metabolismo , Riñón/efectos de los fármacos , Riñón/patología , Células de Riñón Canino Madin Darby , Masculino , Nefrolitiasis/patología , Oxalatos/efectos adversos , Oxalatos/farmacología , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Proteína Gla de la Matriz

RESUMEN

PURPOSE: The purpose of our study was to determine if a hydroxyproline (HP) or gelatin diet could induce long-term hyperoxaluria in the porcine model. MATERIALS AND METHODS: A total of 18 gravid crossbred sows (Large White × Landrace) were randomly allotted into three treatment groups: 5% HP, 10% HP, and gelatin diet. All sows were catheterized 1 day before starting treatment diet. Catheters were left in place for 5 days before being removed. Sows were recatheterized for urine collections on days 11 to 12 and days 21 to 22. Urine was collected for each entire 24-hour period, and urinary oxalate was determined by ion chromatography. RESULTS: Urinary oxalate concentrations for all three diets peaked within the first 5 days of the diet. The sows fed the 5% HP, 10% HP, and gelatin diets had an early peak in urinary oxalate concentration (mg/L) at day 2 (158% increase), day 5 (316% increase), and day 5 (830% increase), respectively. The day 21 to 22 time points in all three diets demonstrated markedly increased urinary oxalate concentrations in comparison with baseline, with some concentrations higher than the early time point peaks (day 22: 5% HP=1906% increase, P=0.12; 10% HP=640% increase, P=0.02; gelatin=501% increase, P=0.01). CONCLUSION: Although both the 10% HP and gelatin diets induce significant short- and long-term hyperoxaluria in the porcine model, the gelatin diet is more cost-effective. The ability to induce long-term hyperoxaluria has important implications in establishing a porcine model for oxalate urolithiasis.

Asunto(s)

Dieta/efectos adversos , Modelos Animales de Enfermedad , Hiperoxaluria/inducido químicamente , Sus scrofa , Animales , Cateterismo , Gelatina/efectos adversos , Hidroxiprolina/efectos adversos , Oxalatos/orina , Factores de Tiempo

RESUMEN

Ethylene glycol (EG) exposure is a common model for kidney stones, because animals accumulate calcium oxalate monohydrate (COM) in kidneys. Wistar rats are more sensitive to EG than Fischer 344 (F344) rats, with greater COM deposition in kidneys. The mechanisms by which COM accumulates differently among strains are poorly understood. Urinary proteins inhibit COM adhesion to renal cells, which could alter COM deposition in kidneys. We hypothesize that COM accumulates more in Wistar rat kidneys because of lower levels of inhibitory proteins in urine. Wistar and F344 rats were treated with 0.75% EG in drinking water for 8 wk. Twenty-four-hour urine was collected every 2 wk for analysis of urinary proteins. Similar studies were conducted for 2 wk using 2% hydroxyproline (HP) as an alternative oxalate source. Total urinary protein was higher in F344 than Wistar rats at all times. Tamm-Horsfall protein was not different between strains. Osteopontin (OPN) levels in Wistar urine and kidney tissue were higher and were further increased by EG treatment. This increase in OPN occurred before renal COM accumulation. Untreated F344 rats showed greater CD45 and ED-1 staining in kidneys than untreated Wistars; in contrast, EG treatment increased CD45 and ED-1 staining in Wistars more than in F344 rats, indicating macrophage infiltration. This increase occurred in parallel with the increase in OPN and before COM accumulation. Like EG, HP induced markedly greater oxalate concentrations in the plasma and urine of Wistar rats compared with F344 rats. These results suggest that OPN upregulation and macrophage infiltration do not completely protect against COM accumulation and may be a response to crystal retention. Because the two oxalate precursors, EG and HP, produced similar elevations of oxalate, the strain difference in COM accumulation may result more so from metabolic differences between strains than from differences in urinary proteins or inflammatory responses.

Asunto(s)

Glicol de Etileno/efectos adversos , Cálculos Renales/inducido químicamente , Cálculos Renales/epidemiología , Mucoproteínas/orina , Osteopontina/orina , Animales , Oxalato de Calcio/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Glicol de Etileno/farmacología , Hidroxiprolina/efectos adversos , Hidroxiprolina/farmacología , Riñón/metabolismo , Masculino , Ratas , Ratas Endogámicas F344 , Ratas Wistar , Factores de Riesgo , Especificidad de la Especie , Uromodulina

RESUMEN

Anoectochilus formosanus is used in traditional folk medicine as an hepatoprotective agent. The purpose of this study was to investigate the effects of a standardized aqueous extract of A. formosanus (SAEAF) on thioacetamide (TAA)-induced liver fibrosis. An in vitro study showed that the inhibitive effect of kinsenoside, a major component of SAEAF, on tumor necrosis factor alpha (TNF-alpha) secretion from Kupffer cells might be derived at least partly from downregulation of LPS-receptor Toll-like receptor 4 (TLR4) signaling. Hepatic fibrosis was produced by TAA (200 mg/kg, i.p.) 3 times per week for 12 weeks. Mice in the three TAA groups were treated daily with distilled water and SAEAF (1.0, 0.2 g/kg) via gastrogavage throughout the experimental period. The mice that received the SAEAF treatment had significantly reduced plasma alanine aminotransferase activity, relative liver weights, and hepatic hydroxyproline contents. A histological examination also confirmed that SAEAF reduced the degree of fibrosis caused by TAA treatment. RT-PCR analysis showed that SAEAF treatment reduced mRNA expression of collagen (alpha1)(I), lipopolysaccharide-binding protein, CD14, TLR4, and TNF receptor 1. An immunohistochemical examination also indicated that SAEAF reduced the number of CD68-positive cells (macrophages). In conclusion, oral administration of SAEAF significantly reduced TAA-induced hepatic fibrosis in mice, probably through inhibition of hepatic Kupffer cell activation.

Asunto(s)

Macrófagos del Hígado/metabolismo , Cirrosis Hepática/patología , Proteínas de Fase Aguda , Animales , Antígenos CD/metabolismo , Antígenos CD/farmacología , Antígenos de Diferenciación Mielomonocítica/metabolismo , Proteínas Portadoras , Regulación hacia Abajo/efectos de los fármacos , Hidroxiprolina/efectos adversos , Hidroxiprolina/metabolismo , Lipopolisacáridos/efectos adversos , Lipopolisacáridos/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/metabolismo , Masculino , Medicina Tradicional , Glicoproteínas de Membrana , Ratones , Ratones Endogámicos BALB C , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Tioacetamida/efectos adversos , Tioacetamida/metabolismo , Tioacetamida/farmacología , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

Objetivo: Comparar os efeitos da neuroestimulação elétrica transcutânea (TENS) e cinesiologia aplicada, assim como esta isolada, na excreção urinária em indivíduos com a síndrome do impacto do ombro (SIO). Métodos: Participaram do estudo dois grupos de 35 indivíduos cada, sendo 30 mulheres e 40 homens, com idade entre 45 e 60 anos. O grupo controle realizou a cinesiologia aplicada e o grupo experimental realizou o tratamento TENS associado à cinesiologia aplicada. Para a mensuração da hidroxiprolina na urina foi utilizado o protocolo de colorimetria. A coleta urinária foi feita na 1ª, 5ª e 10ª sessão. O tratamento foi realizado em 10 sessões de 55 minutos. O tratamento estatístico utilizado foi feito através da análise de variância One Way (ANOVA). Resultado: Não houve melhora significativa como indicado por F = 0,662, p > 0,05. Conclusão: Os resultados mostraram não haver interação significativa entre os tipos de tratamento com a excreção urinária de hidroxiprolina. Contudo, os resultados obtidos das variáveis mostraram uma forte tendência à melhora, apresentando um resultado mais efetivo no grupo que utilizou somente a cinesiologia aplicada até a quinta sessão e, posteriormente, com uma tendência mais efetiva no grupo que utilizou a cinesiologia aplicada + TENS. O estudo mostrou, também, um resultado mais eficiente do grupo que utilizou apenas a cinesiologia aplicada como tratamento.

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Objective: To compare the transcutaneous electrical nerve stimulator (TENS) effects associated to the kinesiology applied, and only the kinesiology applied on the hydroxiproline (HP) excretion on individuals with shoulder pain, during 10 physical therapy sessions with duration of 55 minutes each session for both treatments. Methods: The individuals were divided into two groups of 35 people each, being 30 women and 40 men; aged between 40 and 65 years old. The control group underwent only applied kinesiology and the experimental group applied kinesiology associated to TENS. It was used the colorimetric protocol to measure urinary excretion of HP. Three samples of each variable were carried out on the first, fifth and tenth sessions. The ANOVA test with repeated measures to analyze the HP was used for the statistics. Results: There were no significance as indicated by F = 0.662, p > 0.05. Conclusion: We concluded that the study showed a strong benefit tendency for both groups due to HP decrease levels. As a better result before the 5th session for the group applied kinesiology and after the 5th - 10th session of treatment, for the applied kinesiology + TENS group, although there was no significance based on the statistics. And, also, it showed a better result for the group who practiced only applied kinesiology

Asunto(s)

Colorimetría , Quinesiología Aplicada/instrumentación , Quinesiología Aplicada/métodos , Quinesiología Aplicada , Hidroxiprolina/análisis , Hidroxiprolina/efectos adversos , Hidroxiprolina/orina

RESUMEN

In order to compare the effects of several experimental renal calcium oxalate stones formation models in rats and to find a simple and convenient model with significant effect of calcium oxalate crystals deposition in the kidney, several rat models of renal calcium oxalate stones formation were induced by some crystal-inducing drugs (CID) including ethylene glycol (EG), ammonium chloride (AC), vitamin D(3)[1alpha(OH)VitD(3), alfacalcidol], calcium gluconate, ammonium oxalate, gentamicin sulfate, L-hydroxyproline. The rats were fed with drugs given singly or unitedly. At the end of experiment, 24-h urines were collected and the serum creatinine (Cr), blood urea nitrogen (BUN), the extents of calcium oxalate crystal deposition in the renal tissue, urinary calcium and oxalate excretion were measured. The serum Cr levels in the stone-forming groups were significantly higher than those in the control group except for the group EG+L-hydroxyproline, group calcium gluconate and group oxalate. Blood BUN concentration was significantly higher in rats fed with CID than that in control group except for group EG+L-hydroxyproline and group ammonium oxalate plus calcium gluconate. In the group of rats administered with EG plus Vitamin D(3), the deposition of calcium oxalate crystal in the renal tissue and urinary calcium excretion were significantly greater than other model groups. The effect of the model induced by EG plus AC was similar to that in the group induced by EG plus Vitamin D(3). EG plus Vitamin D(3) or EG plus AC could stably and significantly induced the rat model of renal calcium oxalate stones formation.

Asunto(s)

Oxalato de Calcio/orina , Cálculos Renales/metabolismo , Riñón/metabolismo , Cloruro de Amonio/efectos adversos , Cloruro de Amonio/metabolismo , Cloruro de Amonio/orina , Animales , Nitrógeno de la Urea Sanguínea , Calcio/sangre , Calcio/metabolismo , Calcio/orina , Gluconato de Calcio/efectos adversos , Gluconato de Calcio/metabolismo , Gluconato de Calcio/orina , Oxalato de Calcio/metabolismo , Creatinina/sangre , Cristalización , Modelos Animales de Enfermedad , Glicol de Etileno/efectos adversos , Glicol de Etileno/metabolismo , Glicol de Etileno/orina , Gentamicinas/efectos adversos , Gentamicinas/metabolismo , Gentamicinas/orina , Hidroxicolecalciferoles/efectos adversos , Hidroxicolecalciferoles/metabolismo , Hidroxicolecalciferoles/orina , Hidroxiprolina/efectos adversos , Hidroxiprolina/metabolismo , Hidroxiprolina/orina , Riñón/patología , Cálculos Renales/inducido químicamente , Cálculos Renales/prevención & control , Magnesio/metabolismo , Magnesio/orina , Masculino , Microscopía de Polarización , Oxalatos/efectos adversos , Oxalatos/metabolismo , Oxalatos/orina , Fósforo/sangre , Distribución Aleatoria , Ratas , Ratas Wistar

RESUMEN

A number of animal models have been developed to investigate calcium oxalate (CaOx) nephrolithiasis. Ethylene glycol (EG)-induced hyperoxaluria in rats is most common, but is criticized because EG and some of its metabolites are nephrotoxic and EG causes metabolic acidosis. Both oxalate (Ox) and CaOx crystals are also injurious to renal epithelial cells. Thus, it is difficult to distinguish the effects of EG and its metabolites from those induced by Ox and CaOx crystals. This study was performed to investigate hydroxy-L-proline (HLP), a common ingredient of many diets, as a hyperoxaluria-inducing agent. In rats, HLP has been shown to induce CaOx nephrolithiasis in only hypercalciuric conditions. Five percent HLP mixed with chow was given to male Sprague-Dawley rats for 63 days, resulting in hyperoxaluria, CaOx crystalluria, and nephrolithiasis. Crystal deposits were surrounded by ED-1-positive inflammatory cells. Cell injury and death was followed by regeneration, as suggested by an increase in proliferating cell nuclear antigen-positive cells. Both osteopontin (OPN) and CD44 were upregulated. Staining for CD44 and OPN was intense in cells lining the tubules that contained crystals. Along with a rise in urinary Ox and lactate dehydrogenase, there were significant increases in 8-isoprostane and hydrogen peroxide excretion, indicating that the oxidative stress induced cell injury. Thus, HLP-induced hyperoxaluria alone can induce CaOx nephrolithiasis in rats.

Asunto(s)

Oxalato de Calcio/metabolismo , Hidroxiprolina/efectos adversos , Hiperoxaluria/inducido químicamente , Cálculos Renales/inducido químicamente , Animales , Calcio/orina , Creatinina/orina , Dinoprost/análogos & derivados , Dinoprost/orina , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Receptores de Hialuranos/genética , Receptores de Hialuranos/metabolismo , Peróxido de Hidrógeno/orina , Hiperoxaluria/metabolismo , Hiperoxaluria/patología , Inmunohistoquímica , Cálculos Renales/metabolismo , Cálculos Renales/patología , Túbulos Renales/metabolismo , Túbulos Renales/patología , L-Lactato Deshidrogenasa/orina , Masculino , Osteopontina , Oxalatos/orina , Ratas , Ratas Sprague-Dawley , Sialoglicoproteínas/genética , Sialoglicoproteínas/metabolismo

Asunto(s)

Industria Química , Polvo/análisis , Depuradores de Radicales Libres/análisis , Hidroxiprolina/química , Caolín/química , Enfermedades Profesionales/inducido químicamente , Exposición Profesional/efectos adversos , Depuradores de Radicales Libres/metabolismo , Humanos , Hidroxiprolina/efectos adversos , Técnicas In Vitro , Caolín/efectos adversos , Modelos Químicos , Neumoconiosis/etiología , Neumoconiosis/metabolismo

RESUMEN

Lung fibrosis is a common side effect of the chemotherapeutic agent, bleomycin. Current evidence suggests that reactive oxygen species may play a key role in the development of lung fibrosis. The present study examined the effect of mesna on bleomycin-induced lung fibrosis in rats. Animals were divided into three groups: (1) saline control group; (2) Bleomycin group in which rats were injected with bleomycin (15 mg/kg, i.p.) three times a week for four weeks; (3) Bleomycin and mesna group, in which mesna was given to rats (180 mg/kg/day, i.p.) a week prior to bleomycin and daily during bleomycin injections for 4 weeks until the end of the treatment. Bleomycin treatment resulted in a pronounced fall in the average body weight of animals. Bleomycin-induced pulmonary injury and lung fibrosis was indicated by increased lung hydroxyproline content, and elevated nitric oxide synthase, myeoloperoxidase, platelet activating factor, and tumor necrosis factor-alpha in lung tissues. On the other hand, bleomycin induced a reduction in reduced glutathione concentration and angiotensin converting enzyme activity in lung tissues. Moreover, bleomycin-induced severe histological changes in lung tissues revealed as lymphocytes and neutrophils infiltration, increased collagen deposition and fibrosis. Co-administration of bleomycin and mesna reduced bleomycin-induced weight loss and attenuated lung injury as evaluated by the significant reduction in hydroxyproline content, nitric oxide synthase activity, and concentrations of myeoloperoxidase, platelet activating factor, and tumor necrosis factor-alpha in lung tissues. Furthermore, mesna ameliorated bleomycin-induced reduction in reduced glutathione concentration and angiotensin activity in lung tissues. Finally, histological evidence supported the ability of mesna to attenuate bleomycin-induced lung fibrosis and consolidation. Thus, the findings of the present study provide evidence that mesna may serve as a novel target for potential therapeutic treatment of lung fibrosis.

Asunto(s)

Bleomicina/efectos adversos , Mesna/efectos adversos , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Animales , Bleomicina/administración & dosificación , Bleomicina/antagonistas & inhibidores , Esquema de Medicación , Ensayos de Selección de Medicamentos Antitumorales , Glutatión/antagonistas & inhibidores , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Hidroxiprolina/efectos adversos , Hidroxiprolina/química , Hidroxiprolina/metabolismo , Inyecciones Intraperitoneales , Pulmón/química , Pulmón/efectos de los fármacos , Pulmón/ultraestructura , Masculino , Mesna/administración & dosificación , Mesna/farmacocinética , Óxido Nítrico Sintasa/química , Óxido Nítrico Sintasa/metabolismo , Peptidil-Dipeptidasa A/efectos de los fármacos , Peptidil-Dipeptidasa A/metabolismo , Peroxidasa/efectos de los fármacos , Peroxidasa/metabolismo , Factor de Activación Plaquetaria/efectos de los fármacos , Factor de Activación Plaquetaria/metabolismo , Fibrosis Pulmonar/fisiopatología , Ratas , Ratas Wistar , Factores de Tiempo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Aumento de Peso/efectos de los fármacos , Pérdida de Peso/efectos de los fármacos

RESUMEN

The therapeutic equivalence and safety of treatment for 21 days with 400 mg t.i.d. oxaceprol (n = 132) and 50 mg t.i.d. diclofenac (n = 131) were assessed in a multicentre, randomised, double-blind study of a mixed population of patients with osteoarthritis of the knee and/or hip. In a per-protocol analysis of efficacy, the mean Lequesne index decreased by 2.5 points in the oxaceprol group (n = 109) and by 2.8 points in the diclofenac group (n = 109). The 95% confidence interval for the end-point difference revealed therapeutic equivalence. This was confirmed by assessments (visual analogue scale) of pain at rest, weight-bearing pain, pain on standing and pain on movement, all of which decreased to a similar extent under both treatments. The pain-free walking time increased in both groups from 10 min to 25 min by the end of the treatment period. Mobility was also increased to a similar extent by both drugs. The physicians assessed treatment as good or very good in 45-46% of patients in both groups. In all patients who received treatment, 28 and 37 adverse events were reported by 25 out of 132 (18.9%) and 33 out of 131 (25.2%) patients treated with oxaceprol and diclofenac, respectively. In 15 patients (11.4%) with 15 adverse events in the oxaceprol group and 25 patients (19.1%) with 27 adverse events in the diclofenac group, a relation to the medication was considered probable. The difference between the groups was statistically significant (p = 0.04106) for the number of these adverse events. Oxaceprol is therapeutically equivalent to diclofenac, but better tolerated than diclofenac in the treatment of osteoarthritis.

Asunto(s)

Antiinflamatorios no Esteroideos/uso terapéutico , Diclofenaco/uso terapéutico , Hidroxiprolina/análogos & derivados , Osteoartritis de la Cadera/tratamiento farmacológico , Osteoartritis de la Rodilla/tratamiento farmacológico , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/farmacocinética , Artralgia/tratamiento farmacológico , Artralgia/fisiopatología , Diclofenaco/efectos adversos , Diclofenaco/farmacocinética , Método Doble Ciego , Femenino , Humanos , Hidroxiprolina/efectos adversos , Hidroxiprolina/farmacocinética , Hidroxiprolina/uso terapéutico , Masculino , Persona de Mediana Edad , Osteoartritis de la Cadera/metabolismo , Osteoartritis de la Rodilla/metabolismo , Dimensión del Dolor , Seguridad , Equivalencia Terapéutica , Soporte de Peso

Asunto(s)

Antiinflamatorios no Esteroideos/efectos adversos , Anticoagulantes/efectos adversos , Hidroxiprolina/análogos & derivados , Fenindiona/análogos & derivados , Anciano , Interacciones Farmacológicas/fisiología , Femenino , Humanos , Hidroxiprolina/efectos adversos , Fenindiona/efectos adversos

Asunto(s)

Oxalatos/orina , Cálculos Urinarios , Lesión Renal Aguda/inducido químicamente , Oxidorreductasas de Alcohol/metabolismo , Animales , Asia Sudoriental , Calcio/orina , Fenómenos Químicos , Química , Femenino , Glicoles/envenenamiento , Humanos , Hidroxiprolina/efectos adversos , Lactante , L-Lactato Deshidrogenasa/metabolismo , Síndromes de Malabsorción/complicaciones , Masculino , Metoxiflurano/efectos adversos , Músculos/enzimología , NAD/metabolismo , Oryza/efectos adversos , Oxalatos/sangre , Oxalatos/metabolismo , Deficiencia de Tiamina/complicaciones , Cálculos Urinarios/inducido químicamente , Cálculos Urinarios/metabolismo , Deficiencia de Vitamina B 6/complicaciones