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Taurine, a non-essential amino acid produced from cysteine, is abundant in body tissues and blood plasma. It plays vital roles in growth, osmosis, lipid metabolism, and neurohormonal modulation. Taurine has antioxidant, anti-apoptotic, and anti-inflammatory properties, and its deficiency can lead to various diseases including cardiovascular, diabetic, renal, and liver disorders. This report provides a comprehensive review of the functional properties of taurine in counteracting pharmaceutical-induced side effects. A search across databases such as Scopus, PubMed, MEDLINE, and Web of Science yielded 109 articles, of which 75 were included in the study. These results suggest that the protective effects of taurine involve mechanisms such as influencing pathways of Nrf2/OH-1, PI3-kinase/AKT and ERK2, boosting antioxidants (SOD, GPx and CAT), and suppression of inflammatory cytokines (TNF-α, IL-1ß and IL-6). Overall, supplementation with taurine along with medications with significant side effects may mitigate these effects and enhance their efficacy. Further investigation of the interactions between taurine and other nutrients or compounds may provide insights into synergistic effects and novel therapeutic approaches.

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Objective: Acrylamide (ACR) is a neurotoxic agent whose damage could be attenuated by antioxidants administration. Crocetin is a saffron-derived antioxidant that has neuroprotective effects. This study evaluates the protective effects of trans-sodium crocetinate (TSC) and its water-soluble derivative, Bis-N-(N-methylpyprazinyl) crocetinate (BMPC) against ACR neurotoxicity. Materials and Methods: PC12 cells were treated with TSC and BMPC (1.95, 3.9, 7.81, 15.62, 31.25, 62.5, 125, 250, 500, and 1000 µM) for 24 hr. ACR was then added at a concentration of 6.5 mM (IC50), and cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide. In the in vivo study, male Wistar rats were treated with ACR (50 mg/kg, intraperitoneal (i.p.)) for 11 days alone or in combination with TSC and BMPC (2.5, 5, and 10 mg/kg, i.p.) or vitamin E (200 IU/kg, i.p.). Motor impairments were then evaluated. The cerebral cortex of sacrificed rats was taken for the malondialdehyde (MDA) and glutathione (GSH) levels measurement. Results: In vitro studies showed that TSC at a concentration of 7.81 µM and BMPC at concentrations of 3.9, 7.81, and 15.62 µM exhibited the lowest toxicity in acrylamide administration. In the in vivo study, pretreatment with 2.5, 5, and 10 mg/kg of TSC ameliorated behavioral impairments, but BMPC could not attenuate them. GSH and MDA were improved by 2.5, 5, and 10 mg/kg TSC and 2.5 mg/kg BMPC. Conclusion: TSC and BMPC administration improved behavioral index and oxidative stress injuries in Wistar rats exposed to ACR through MDA reduction and GSH content enhancement in the cerebral cortex.

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Colistin, a multidrug-resistant gram-negative bacterial infection medication, has been associated with renal impairment and failure. Trans-sodium crocetinate (TSC), a saffron-derived chemical recognized for its antioxidant and nephroprotective properties, was studied in this study to determine its potential to alleviate the nephrotoxic effects of colistin. Forty-two male Wistar rats were randomly classified into seven groups (n = 6): (1) control (normal saline, 12 days, i.p.), (2) colistin (22 mg/kg, 7 days, i.p.), (3-5) colistin + TSC (25, 50, and 100 mg/kg, 12 days, i.p., starting from 5 days before colistin), (6) TSC (100 mg/kg, 12 days, i.p.), (7) colistin + vitamin E (100 IU/kg, 12 days, i.p). On day 13, the rats were euthanized and the serum content of creatinine, BUN, Na+, and K+, as well as oxidative stress (GSH, MDA, SOD, CAT), inflammatory (IL-1ß), apoptotic (Bax, Bcl-2, caspase-3, 8, 9), and autophagy (Beclin-1, LC3) markers, NGAL, and histopathological changes in the kidney were measured. Colistin significantly increased serum creatinine, BUN, MDA, IL-1ß, caspase-3,8,9, Bax, Beclin-1, LC3, and NGAL levels in kidney tissue. It also caused inflammation, focal necrosis of tubular epithelial cells, protein cast, and acute tubular necrosis. Furthermore, colistin decreased SOD, CAT, GSH, and Bcl-2 levels. TSC and vitamin E administration along with colistin restored most of the alterations induced by colistin. Overall, it could be concluded that colistin induces oxidative stress, inflammation, autophagy, and apoptosis, which can cause kidney injury. However, TSC can also be used as a therapeutic agent to reduce injuries caused by colistin.

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Taurine is a non-proteinogenic amino acid derived from cysteine. It is involved in several phenomena such as the regulation of growth and differentiation, osmoregulation, neurohormonal modulation, and lipid metabolism. Taurine is important because of its high levels in several tissues such as the central nervous system (CNS), heart, skeletal muscles, retinal membranes, and platelets. In this report, we present the functional properties of taurine indicating that it has potential effects on various metal toxicities. Therefore, a comprehensive literature review was performed using the Scopus, PubMed, and Web of Science databases. According to the search keywords, 61 articles were included in the study. The results indicate that taurine protects tissues against metal toxicity through enhancement of enzymatic and non-enzymatic antioxidant capacity, modulation of oxidative stress, anti-inflammatory and anti-apoptotic effects, involvement in different molecular pathways, and interference with the activity of various enzymes. Taken together, taurine is a natural supplement that presents antitoxic effects against many types of compounds, especially metals, suggesting public consumption of this amino acid as a prophylactic agent against the incidence of metal toxicity.

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Multiple sclerosis (MS) is an autoimmune disorder characterized by the degeneration of myelin and inflammation in the central nervous system. Trans sodium crocetinate (TSC), a novel synthetic carotenoid compound, possesses antioxidant, anti-inflammatory and neuroprotective effects. This study aimed to evaluate the protective effects of TSC against the development of experimental autoimmune encephalomyelitis (EAE), a well-established model for MS. Female BALB/C57 mice were divided into different groups, including control, EAE, vehicle, TSC-treated (25, 50, and 100 mg/kg, administered via gavage) + EAE, methyl prednisone acetate + EAE, and TSC-treated (100 mg/kg, administered via gavage for 28 days) groups. EAE was induced using MOG35-55, complete Freund's adjuvant, and pertussis toxin. In the mice spinal cord tissues, the oxidative markers (GSH and MDA) were measured using spectrophotometry and histological evaluation was performed. Mitophagic pathway proteins (PINK1and PARKIN) and inflammatory factors (IL-1ß and TNF-α) were evaluated by western blot. Following 21 days post-induction, EAE mice exhibited weight loss, and the paralysis scores increased on day 13 but recovered after TSC (100 mg/kg) administration on day 16. Furthermore, TSC (50 and 100 mg/kg) reversed the altered levels of MDA and GSH in the spinal cord tissue of EAE mice. TSC (100 mg/kg) also decreased microgliosis, demyelination, and the levels of inflammatory markers IL-1ß and TNF-α. Notably, TSC (100 mg/kg) modulated the mitophagy pathway by reducing PINK1 and Parkin protein levels. These findings demonstrate that TSC protects spinal cord tissue against EAE-induced MS through anti-inflammatory, antioxidant, and anti-mitophagy mechanisms.

Asunto(s)

Antiinflamatorios , Antioxidantes , Carotenoides , Encefalomielitis Autoinmune Experimental , Ratones Endogámicos BALB C , Vitamina A , Animales , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Ratones , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Femenino , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Carotenoides/farmacología , Carotenoides/uso terapéutico , Vitamina A/análogos & derivados , Vitamina A/uso terapéutico , Ratones Endogámicos C57BL , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Médula Espinal/patología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Factor de Necrosis Tumoral alfa/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Interleucina-1beta/metabolismo

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PURPOSE: The most important problem with acetaminophen is its hepatotoxicity. N-acetylcysteine (NAC) is used to treat the hepatotoxicity of acetaminophen. Due to the structural similarities of this compound with amifostine, we decided to test the effect of this substance and its metabolite, WR-1065, on the hepatotoxicity of acetaminophen. METHODS: The single-dose method contained 1. Control; 2. Acetaminophen (1 g/kg, gavage); 3-5. Acetaminophen + amifostine (100, 200, 400 mg/kg, i.p.); 6-8. Acetaminophen + WR-1065 (50, 100, 200 mg/kg, i.p.); and 9. Acetaminophen + NAC (100, 200 mg/kg, i.p.). The multiple-dose method included the same groups: amifostine (50, 100, 200 mg/kg), WR-1065 (25, 50, 100 mg/kg), and NAC (100 mg/kg). Then, animals were sacrificed, and blood samples were collected for measuring ALT, AST, ALP, and T-Bil, liver tissue for histopathological examination, MDA, and GSH amounts. RESULTS: Acetaminophen increased the levels of MDA, T-Bil, ALT, AST, and ALP, decreased GSH levels, and augmented necrosis, neutrophils, lymphocytes, and macrophages in the port space in single-dose and multiple-dose studies. Amifostine and WR-1065 significantly reduced the levels of MDA, T-Bil, ALT, AST, ALP, increased GSH content, and ameliorated histopathological alterations in a single-dose and multiple-dose method compared to the acetaminophen group. Moreover, NAC caused a significant decrease in the levels of MDA, T-Bil, ALT, AST, and ALP, and reduced GSH amounts in single-dose and multiple-dose studies. CONCLUSION: Amifostine and WR-1065 as antioxidant and hepatoprotective compounds are effective in reducing acetaminophen-induced hepatotoxicity with a similar effect to NAC and can be administered as an adjunct in the treatment of acetaminophen overdose.

Asunto(s)

Acetaminofén , Amifostina , Enfermedad Hepática Inducida por Sustancias y Drogas , Hígado , Ratas Wistar , Animales , Acetaminofén/toxicidad , Amifostina/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Masculino , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Mercaptoetilaminas/farmacología , Acetilcisteína/farmacología , Ratas , Antioxidantes/farmacología , Analgésicos no Narcóticos/toxicidad , Relación Dosis-Respuesta a Droga , Glutatión/metabolismo , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico

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Objectives: Utilization of doxorubicin (DOX) as a chemotherapy medication is limited due to its cardiotoxic effects. Carnosic acid exerts antioxidant, anti-inflammatory, besides cytoprotective effects. The objective of this study was to investigate the ability of carnosic acid to protect rat hearts and the MCF7 cell line against cardiotoxicity induced by DOX. Materials and Methods: The study involved the classification of male Wistar rats into seven groups: 1) Control 2) DOX (2 mg/kg, every 48h, IP, 12d), 3-5) Carnosic acid (10, 20, 40 mg/kg/day, IP, 16d)+ DOX, 6) Vitamin E (200 mg/kg, every 48h, IP, 16d)+ DOX 7) Carnosic acid (40 mg/kg/day, IP, 16d). Finally, cardiac histopathological alterations, ECG factors, carotid blood pressure, left ventricular function, heart-to-body weight ratio, oxidative (MDA, GSH), inflammatory (IL-1ß, TNF-α), plus apoptosis (caspase 3, 8, 9, Bcl-2, Bax) markers were evaluated. DOX toxicity and carnosic acid ameliorative effect were evaluated on MCF7 cells using the MTT assay. Results: DOX augmented the QRS duration, QA, RRI, STI, and heart-to-body weight ratio, and reduced HR, LVDP, Min dP/dt, Max dP/dt, blood pressure, boosted MDA, TNF-α, IL1-ß, caspase 3,8,9, Bax/Bcl-2 ratio, decreased GSH content, caused fibrosis, necrosis, and cytoplasmic vacuolization in cardiac tissue but carnosic acid administration reduced the toxic effects of DOX. The cytotoxic effects of DOX were not affected by carnosic acid at concentrations of 5 and 10 µM. Conclusion: Carnosic acid as an anti-inflammatory and antioxidant substance is effective in reducing DOX-induced damage by enhancing antioxidant defense and modifying inflammatory signal pathway activity and can be used as an adjunct in treating DOX cardiotoxicity.

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Objectives: Colistin is used to treat multidrug-resistant gram-negative bacterial infections. It increases the membrane permeability of kidney cells, leading to kidney toxicity. Crocin, a carotenoid found in saffron, has anti-oxidant and nephroprotective properties. The present study aimed to explore the potential renoprotective effects of crocin against colistin-induced nephrotoxicity. Materials and Methods: Six groups of male Wistar rats were utilized: 1- Control (0.5 ml of normal saline, 10 days, IP); 2- Crocin (40 mg/kg, 10 days, IP); 3-Colistin (23 mg/kg, 7 days, IP); 4-6 Colistin (23 mg/kg, 7 days, IP)+ crocin (10, 20, 40 mg/kg, 10 days, IP). On day 11, rats were sacrificed and their blood and kidney samples were collected to measure creatinine, blood urea nitrogen (BUN), glutathione (GSH) levels, malondialdehyde (MDA), and histopathological alterations. Results: Colistin caused a significant increase in BUN, creatinine, and MDA, and a decrease in GSH compared to the control group. It also led to congested blood vessels, glomerular shrinkage, and medullary tubular degeneration. Co-administration of crocin with colistin resulted in a significant decrease in BUN and creatinine, increased GSH levels, and ameliorated the histopathological alterations compared to the colistin group. No significant difference was found between the control group and the crocin (40 mg/kg) group. Conclusion: It might be suggested that colistin can induce kidney damage by inducing oxidative stress. However, crocin shows protective effects against colistin-induced renal injury by acting as an anti-oxidant. Hence, crocin can be used as a supplement to reduce tissue and biochemical damage caused by colistin injection.

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Objectives: Diabetes is a chronic disorder that occurs as a result of impaired glucose metabolism. In hyperglycaemic states, the balance between oxidative stress and antioxidant enzymes is disrupted leading to oxidative damage and cell death. In addition, impaired autophagy leads to the storage of dysfunctional proteins and cellular organelles in the cell. Hence, the cytoprotective function of autophagy may be disrupted by high glucose conditions. Alpha-mangostin (A-MG) is an essential xanthone purified from the mangosteen fruit. The different pharmacological benefits of alpha-mangostin, including antioxidant, anti-obesity, and antidiabetic, were demonstrated. Materials and Methods: We evaluated the protective influence of A-MG on autophagic response impaired by high concentrations of glucose in human umbilical vein endothelial cells (HUVECs). The HUVECs were treated with various glucose concentrations (5-60 mM) and A-MG (1.25-10 µM) for three days. Then, HUVECs were treated with 60 mM of glucose+2.5 µM of A-MG to measure viability, ROS, and NO content. Finally, the levels of autophagic proteins including LC3, SIRT1, and beclin 1 were evaluated by western blot. Results: The results expressed that high glucose condition (60 mM) decreased viability and increased ROS and NO content in HUVECs. In addition, LC3, SIRT1, and beclin 1 protein levels declined when HUVECs were exposed to the high concentration of glucose. A-MG reversed these detrimental effects and elevated autophagic protein levels. Conclusion: Our data represent that A-MG protects HUVECs against high glucose conditions by decreasing ROS and NO generation as well as increasing the expression of autophagy proteins.

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BACKGROUND: Acrylamide (ACR) can induce neurotoxicity through different pathways, including oxidative stress and apoptosis. Azithromycin is well-known for its antioxidant and anti-apoptotic properties. OBJECTIVE: To evaluate the potential neuroprotective effect of azithromycin in an in vivo model of ACR-induced neurotoxicity, by investigating its impact on oxidative stress and apoptosis pathways. METHODS: Male rats were divided into eleven groups at random (n = 6). 1:control (vehicle), 2:ACR (50 mg/kg, 11 days, I.P.), 3-7:ACR+ azithromycin (3.1, 6.25, 12.5, 25, 50 mg/kg, 11 days, I.P.), 8-9:ACR+ azithromycin (3.1, 6.25 mg/kg, from day 3-11), 10: ACR+ vitamin E (200 mg/kg, every other day, I.P.), 11. Azithromycin (50 mg/kg). Following the treatment period, a gait score examination was performed, and malondialdehyde (MDA), glutathione (GSH), Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio and caspase-3 levels in the cerebral cortex were measured. RESULTS: Gait abnormality, a drop in GSH, and an increase in lipid peroxidation, Bax/Bcl-2 ratio, and caspase-3 levels were all significantly triggered by ACR in the cerebral cortex versus the control group. Azithromycin 3.1 and 6.25 mg/kg with ACR and azithromycin 6.25 mg/kg with ACR from day 3-11 ameliorated movement disorders caused by ACR. Azithromycin in all doses and both protocols along with ACR decreased the MDA level. Azithromycin (3.1, 6.25 mg/kg) along with ACR in both protocols increased the level of GSH, reduced the Bax/Bcl-2 ratio and caspase-3 amounts in the brain tissue versus the ACR group. CONCLUSIONS: Administration of azithromycin had both preventive and therapeutic effects on ACR-induced neurotoxicity through its antioxidant and antiapoptotic properties.

Asunto(s)

Antioxidantes , Azitromicina , Ratas , Masculino , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/metabolismo , Caspasa 3/metabolismo , Azitromicina/uso terapéutico , Azitromicina/farmacología , Proteína X Asociada a bcl-2/metabolismo , Acrilamida/toxicidad , Estrés Oxidativo , Glutatión/metabolismo , Apoptosis

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BACKGROUND: Olanzapine (OLZ) is an atypical antipsychotic agent for psychotic disorders. Evidence has shown that OLZ is related to metabolic side effects, including obesity, hypertension, and insulin resistance. Thymoquinone (TQ) is the principal bioactive component of Nigella sativa. Several studies have been conducted to investigate the effectiveness of TQ in alleviating metabolic abnormalities. In the current research work, the protective effects of TQ on metabolic disorders induced by OLZ and possible underlying mechanisms were investigated. METHODS AND RESULTS: Wistar rats were exposed to TQ alone (10 mg/kg), OLZ (5 mg/kg), or OLZ plus TQ (2.5, 5, or 10 mg/kg) given daily by intraperitoneal injection. After the treatment, variations in body weight, food intake, systolic blood pressure, serum leptin, biochemical factors, liver malondialdehyde (MDA), and glutathione (GSH) content were evaluated. Protein expression of AMPK in the liver was also measured by a western blotting test. OLZ increased body weight, food intake, MDA levels, and blood pressure. OLZ also elevated glucose, triglyceride, low-density lipoprotein cholesterol, and leptin serum levels. It decreased GSH. In the western blot, decreased AMPK protein level was obtained. These changes were attenuated by TQ co-administration. CONCLUSIONS: The present study demonstrates the effectiveness of TQ on OLZ-induced metabolic abnormalities related to its antioxidant activity and regulation of glucose homeostasis and lipid metabolism.

Asunto(s)

Resistencia a la Insulina , Leptina , Ratas , Animales , Olanzapina/efectos adversos , Proteínas Quinasas Activadas por AMP/metabolismo , Ratas Wistar , Benzoquinonas/farmacología , Glucosa , Obesidad/inducido químicamente

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Safranal (a monoterpene aldehyde) is the major volatile component of saffron which is responsible for the saffron unique odor. Several studies have shown the pharmacological activities of safranal including anti-oxidant, anti-inflammatory, cardioprotective, neuroprotective, nephroprotective, gastrointestinal protective, etc. This study was designed to review the pharmacological and medical effects of safranal and up-to-date previous knowledge. Moreover, some patents related to the pharmacological effects of safranal were gathered. Therefore, electronic databases including Web of Sciences, Scopus, and Pubmed for pharmacological effects and US patent, Patentscope, and Google Patent for patents were comprehensively searched by related English keywords from 2010 to June 2022. According to our review, most of the studies are related to the safranal effects on CNS such as antianxiety, analgesic, anticonvulsant, antiischemic, anti-tremor, memory enhancement and its protective effects on neurodegenerative disorders such as Alzheimer's, Parkinson and Huntington diseases. Other effects of safranal are antiasthmatic, antihypertensive, antiaging, anticataract, etc. Moreover, the protective effects of this agent on metabolic syndrome and diabetic nephropathy have been shown. Different mechanisms including anti-oxidant, anti-inflammatory, muscle relaxation, antiapoptotic, and regulatory effects on the genes and proteins expression related to signaling pathways of oxidative stress, inflammation, apoptosis, proliferation, etc. are involved in safranal pharmacological effects. Some patents for the prevention and/or treatment of different diseases such as liver cancer, sleep disorder, depression, cognitive disorder, obesity and PMS were also included. Based on the documents, safranal is considered a promising therapeutic agent although more clinical studies are needed to verify the beneficial effects of safranal in humans.

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Objectives: Acrylamide (ACR) is an environmental contaminant and neurotoxin. Telmisartan is an AT1 blocker that has neuroprotective properties basically through its anti-oxidant effect. The effect of telmisartan on ACR-induced neurotoxicity was investigated in this study. Materials and Methods: Male Wistar rats were randomly assigned to eight groups (n=6): 1:Control (normal saline), 2:ACR (50 mg/kg, 11 days, IP), 3:ACR+vitamin E (200 mg/kg, every other day, 11 days), 4-6:ACR+telmisartan (0.6, 1.25, and 2.5 mg/kg, 11 days, IP), 7:ACR+telmisartan (0.6 mg/kg, days 3-11), 8:Telmisartan (2.5 mg/kg, 11 days). The behavioral test and blood pressure were assessed after 11 days. Then, the levels of MDA and GSH in brain tissue were measured. The MTT assay was used to evaluate the effect of telmisartan on ACR-induced cytotoxicity. Results: Exposing PC12 cells to ACR decreased cell viability versus the control group. Pretreating PC12 cells with telmisartan (0.0125, 0.025 µM) enhanced cell viability compared with the ACR group. Compared with control samples, ACR significantly caused motor impairment, elevated MDA, and reduced GSH levels. Locomotor abnormalities were significantly ameliorated by telmisartan (0.6, 1.25 mg/kg, 11 days) and vitamin E versus the ACR group. Receiving telmisartan (0.6, 1.25, and 2.5 mg/kg) and vitamin E along with ACR decreased MDA levels and enhanced GSH content compared with the ACR group. There was no significant difference in animal blood pressure between the groups. Conclusion: Oxidative stress has a chief role in the neurotoxicity of ACR. Telmisartan (in doses that do not affect blood pressure) ameliorated ACR-induced toxicity by inhibiting oxidative stress.

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Acrylamide (ACR) is known to be a neurotoxic agent for humans and animals that has many applications in industry. Alpha-mangostin is a natural antioxidant that is extracted from mangosteen. This study aimed to investigate the protective effects of alpha-mangostin against ACR-induced neurotoxicity in rats and PC12 cells. Male Wistar rats were used in this investigation for 11 days, divided into 8 groups: 1. control group (normal saline), 2. ACR (50 mg/kg, i.p.), 3-6. ACR + alpha-mangostin (20, 40, 60 mg/kg, p.o.), 7. ACR + vitamin E (200 mg/kg, i.p., every other day) 8. alpha-mangostin (60 mg/kg, p.o.). On the last day of the study, the behavioral test was performed. The amounts of malondialdehyde (MDA) and glutathione (GSH) were measured. Also, the effects of ACR and alpha-mangostin were assessed by MTT assay on PC12 cells, and the levels of reactive oxygen species (ROS), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved caspase-3 proteins were measured by Western blotting. Receiving ACR caused motor disorders in animals, increased MDA, and decreased GSH levels of the cerebral cortex versus the control group. Alpha-mangostin (60 mg/kg) reduced ACR motility disorders, MDA amounts, and augmented GSH levels. The concurrent administration of vitamin E and ACR reduced gait score, MDA level, and amplified GSH content versus the ACR group. In the in vitro section, alpha-mangostin (1.25 µM, 24 h) increased cell viability, attenuated ROS, Bax/Bcl-2, and cleaved caspase-3 levels versus the ACR group. Alpha-mangostin reduced the toxicity of ACR by inhibiting oxidative stress and apoptosis. Therefore, it could be a promising compound for managing ACR-induced neurotoxicity.

Asunto(s)

Acrilamida , Síndromes de Neurotoxicidad , Humanos , Ratas , Masculino , Animales , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Caspasa 3/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Acrilamida/toxicidad , Estrés Oxidativo , Glutatión/metabolismo , Apoptosis , Vitamina E/farmacología

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Cardiovascular diseases (CVDs) are some of the major causes of death worldwide. The modern lifestyle elevates the risk of CVDs. CVDs have several risk factors such as obesity, dyslipidemia, atherosclerosis, hypertension, and diabetes. Using herbal and natural products plays a pivotal role in the treatment of different diseases such as CVDs, diabetes, and metabolic syndrome. Propolis, a natural resinous mixture, is made by honey bees. Its main components are phenolics and terpenoid compounds such as caffeic acid phenethyl ester, chrysin, and quercetin. In this review, multiple studies regarding the pharmacological impacts of propolis and its constituents with their related mechanisms of action against mentioned CVD risk factors have been discussed in detail. Here, we used electronic databases or search engines such as Scopus, Web of Science, Pubmed, and Google Scholar without time limitations. The primary components of propolis are phenolics and terpenoid compounds such as caffeic acid phenethyl ester, chrysin and quercetin. Propolis and its constituents have been found to exhibit anti-obesity, anti-hypertension, anti-dyslipidemic, anti-atherosclerosis, and anti-diabetic effects. The vast majority of studies discussed in this review demonstrate that propolis and its constituents could have therapeutic effects against mentioned CVD risk factors via several mechanisms such as antioxidant, anti-inflammatory, reducing adipogenesis, HMG-CoA reductase inhibitory effect, inhibition of the ACE, increasing insulin secretion, NO level, etc.

RESUMEN

Objectives: Acrylamide (ACR) is a toxic chemical agent that can induce hepatotoxicity through different mechanisms including oxidative stress and apoptosis. Amifostine is an important hepatoprotective and anti-oxidant compound. In this research, the hepatoprotective effect of amifostine on ACR-induced hepatotoxicity in rats has been investigated. Materials and Methods: Male Wistar rats were randomly divided into 7 groups, including: 1. Control group, 2. ACR (50 mg/kg, 11 days, IP), 3-5. ACR+ amifostine (25, 50, 100 mg/kg, 11 days, IP), 6. ACR+ N-acetyl cysteine (NAC) (200 mg/kg, 11 days, IP), and 7. Amifostine (100 mg/kg, 11 days, IP). At the end of the injection period, animals' liver samples were collected to determine the content of glutathione (GSH), malondialdehyde (MDA), and apoptotic proteins (B-cell lymphoma 2 (Bcl2), Bcl-2-associated X protein (Bax), and cleaved caspase-3. Serum samples were also collected to measure alanine transaminase (ALT) and aspartate transaminase (AST) levels. Results: Administration of ACR increased MDA, Bax/Bcl2 ratio, cleaved caspase-3, ALT, and AST levels, and decreased GSH content compared with the control group. The administration of amifostine with ACR decreased MDA, Bax/Bcl2 ratio, cleaved caspase-3, ALT, and AST levels, and increased GSH content compared with the ACR group. Receiving NAC along with ACR reversed the alterations induced by ACR. Conclusion: This study shows that pretreatment with amifostine can reduce ACR-induced toxicity in the liver tissue of rats. Since oxidative stress is one of the most important mechanisms in ACR toxicity, amifostine probably reduces the toxicity of ACR by increasing the anti-oxidant and anti-apoptotic capacity of the hepatic cells.

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Acute respiratory distress syndrome (ARDS) is a serious intensive care condition. Despite advances in treatment over the previous few decades, ARDS patients still have high fatality rates. Thus, more research is needed to improve the outcomes for people with ARDS. Minocycline is an antibiotic with antioxidant, anti-inflammatory, and anti-apoptotic effects. In the current investigation, the therapeutic effects of minocycline on oleic acid-induced ARDS were evaluated. Male rats were classified into 6 groups, 1. control (normal saline), 2. oleic acid (100 µL, i.v.), 3-5. oleic acid + minocycline (50, 100, 200 mg/kg, i.p.), and 6. minocycline (200 mg/kg, i.p.) alone. Twenty-four hours after the oleic acid injection, the lung tissue is isolated, weighed, and the middle part of the right lung is immediately placed in the freezer, while the middle part of the left lung is placed in formalin and sent to the laboratory for pathology testing. Then, the amounts of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), cytokines (interleukin-1 beta (IL-1ß), tumor necrosis factor-α (TNF-α)), B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X (Bax), and cleaved caspase-3 were determined in lung tissue. Administration of oleic acid increased emphysema, inflammation, vascular congestion, hemorrhage, MDA amount, Bax/Bcl-2 ratio, cleaved caspase-3, IL-1ß, TNF-α levels, and decreased GSH, SOD, and CAT levels in comparison with the control group. The administration of minocycline could significantly reduce pathological and biochemical alterations induced by oleic acid. Minocycline has a therapeutic effect on oleic acid-induced ARDS through antioxidant, anti-inflammatory, and anti-apoptotic properties.

Asunto(s)

Minociclina , Síndrome de Dificultad Respiratoria , Humanos , Ratas , Masculino , Animales , Minociclina/farmacología , Minociclina/uso terapéutico , Ácido Oléico/toxicidad , Caspasa 3 , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Factor de Necrosis Tumoral alfa , Proteína X Asociada a bcl-2 , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Superóxido Dismutasa

RESUMEN

BACKGROUND: Pre-diabetes is a condition in which blood glucose levels are high but not as high as in diabetic patients. However, it can lead to diabetes, making it a serious global health issue. Previous studies have shown that the gut microbiome can affect insulin sensitivity and improve glucose management, which can reduce or delay the progression of pre-diabetes to type 2 diabetes mellitus. This study was designed to investigate the effects of probiotics on glycemic and lipid profile control in pre-diabetic patients. METHODS: This randomized, double-blinded clinical trial was conducted on 70 pre-diabetic patients at the Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran. Participants were divided into two groups, both of which received lifestyle modification training. One of the groups also received 500 mg/day probiotic capsules for three months, while the other group received a placebo. Before and after the three-month period, systolic and diastolic blood pressure, serum insulin level, hemoglobin A1c (HbA1c), fasting blood sugar (FBS), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) were measured and compared using statistical tests to examine the effect of probiotics. RESULTS: A total of 70 individuals participated in the trial, including 50 women (71.4%) and 20 men (28.6%), with an average age of 43.53 ± 8.54 years. At the end of the trial, the mean weight (P < 0.001), FBS (P < 0.001), HbA1c (P = 0.035), TG (P = 0.004), and LDL (P = 0.016) were significantly reduced in the intervention group, while their insulin level (P = 0.041) and HDL (P = 0.001) were significantly increased. However, mean systolic (P = 0.459) and diastolic blood pressure (P = 0.961) and insulin resistance (P = 0.235) did not show any significant difference in the intervention group from the beginning of the study. CONCLUSION: Our study showed that probiotic administration is effective in improving the glucose and lipid profile of pre-diabetic patients. However, it was not significantly different from the placebo.

RESUMEN

Statement of the Problem: One of the rare adverse effects in patients who take bisphosphonates is the osteonecrosis of the jaw in the oral cavity following any trauma such as tooth extraction. Purpose: The aim of this study is the histopathological evaluation of the jaw following intra-ligament anesthesia injection in Zoledronate-treated rats. Materials and Method: In this descriptive-experimental study, rats weighing 200-250 g were divided into 2 groups. The first group received a 0.6 mg/kg dose of zoledronate and the second group received normal saline. Five injections with a 28-day interval were performed. At the end of the injection, the animals were sacrificed. Then, five-micrometer histological slides were prepared from the first maxillary molars and the surrounding tissues. Hematoxylin and eosin staining was performed to evaluate osteonecrosis, infiltration of inflammatory cells, fibrosis, and root and bone resorption. Results: There was no difference between the macroscopic and clinical features in both groups and no evidence of osteonecrosis of the jaw was observed in the samples. From the histological point of view, all the samples had normal tissues and none of them showed any evidence of inflammation, tissue fibrosis, disorder, or pathological root resorption. Conclusion: According to the histological findings, the periodontal ligament space, the bone adjacent to the roots, and the dental pulp conditions were similar in both groups. Osteonecrosis of the jaw did not develop in the rats that took bisphosphonates after intraligamental injection.

RESUMEN

Objectives: Contrast media (CM) are used for diagnostic or therapeutic intervention purposes in medicine. The main adverse reaction after the administration of CM is contrast-induced nephropathy (CIN). This complication is the third cause of renal failure after hospital treatment. The current study is designed to investigate the possible protective effect of trans-sodium crocetinate (TSC), derived from carotenoid crocetin, against sodium amidotrizoate/meglumine amidotrizoate (SAMA) induced cytotoxicity in HEK-293 cells. Materials and Methods: HEK-293 cells were incubated with different concentrations of TSC (1, 2.5, 5, 10, 25, and 50 µM, for 48 hr) and then SAMA (7 mgI/ml, for 24 hr) was added. The cell viability, intracellular ROS, and phosphatidyl serine exposure were detected by MTT assay, DCFH-DA, and annexin V-FITC/PI method, respectively. The P-ERK/ERK ratio, apoptosis (Bax/Bcl-2 ratio and cleaved caspase-3), and autophagy (LC3 II/I ratio and beclin-1) markers in cells were evaluated by the western blot method. Results: The exposure of HEK-293 cells to SAMA reduced viability, increased apoptotic cells, enhanced ROS production, and subsequently decreased P-ERK/ERK ratio. Similarly, SAMA enhanced apoptosis (Bax/Bcl-2 ratio and cleaved caspase-3) and autophagy (LC3 II/I ratio and beclin-1) markers in HEK-293 cells. The pretreatment of cells with TSC before exposure to SAMA significantly attenuated contrast-induced cytotoxicity. TSC reduced intracellular ROS production and activated the phosphorylation of ERK. In addition, TSC decreased the levels of apoptosis and autophagy proteins. Conclusion: The pretreatment of HEK-293 cells with TSC can decrease contrast-induced cytotoxicity through antioxidant effect and modulate ERK, apoptosis, and autophagy pathways.