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Icariin (ICA), one of the main active components of Herba Epimedii, is a natural prenylated flavonol glycoside that possesses a wide range of pharmacological effects, including antioxidant, antiosteoporotic, anti-aging, neuroprotective, immunomodulatory, antitumor, and aphrodisiac effects, and prevents numerous health disorders, such as cardiovascular diseases, osteoporosis, cancer, sexual dysfunction, menstrual disorders, neurodegenerative diseases, asthma, chronic inflammation, and diabetes. In the reproductive system, it has been observed that ICA may play a role in preserving fertility by regulating different signalling pathways, such as PI3K/AKT, which improves ovarian function, and ERα/Nrf2, which enhances testicular function and prevents ROS generation. In contrast, regulating the NF/kB signalling pathway causes anti-inflammatory effects, reducing spontaneous abortions. In this study, we review and examine the relevant literature on the therapeutic potential of ICA in reproduction, highlight the various mechanisms of action and limitations for the therapeutic applications of ICA, and summarise and highlight the existing preclinical research on its effects on male and female reproduction.
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Plants of the genus Opuntia spp are widely distributed in Africa, Asia, Australia and America. Specifically, Mexico has the largest number of wild species; mainly O. streptacantha, O. hyptiacantha, O. albicarpa, O. megacantha and O. ficus-indica. The latter being the most cultivated and domesticated species. Its main bioactive compounds include pigments (carotenoids, betalains and betacyanins), vitamins, flavonoids (isorhamnetin, kaempferol, quercetin) and phenolic compounds. Together, they favor the different plant parts and are considered phytochemically important and associated with control, progression and prevention of some chronic and infectious diseases. Part 1 collected information on its preventive actions against atherosclerotic cardiovascular diseases, diabetes and obesity, hepatoprotection, effects on human infertility and chemopreventive capacity. Now, this second review (Part 2), compiles the data from published research (in vitro, in vivo, and clinical studies) on its neuroprotective, anti-inflammatory, antiulcerative, antimicrobial, antiviral potential and in the treatment of skin wounds. The aim of both reviews is to provide scientific evidences of its beneficial properties and to encourage health professionals and researchers to expand studies on the pharmacological and therapeutic effects of Opuntia spp.
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Cadmium is a metal that can affect the male reproductive process, possibly leading to infertility. In contrast, beta-caryophyllene (BC) is a sesquiterpene that has shown antigenotoxic, anticancer, and antioxidant properties. Therefore, the aim of the present study was to determine the protective effect of BC against the deleterious effects of cadmium chloride (CC) on various mouse testicular and sperm parameters. We tested three doses of BC (20, 200, and 400 mg/kg) given before and during exposure to 3 mg/kg CC (six days after a single administration). Our results show significant alleviation of the damage induced by CC after the three doses of BC. Regarding the sperm concentration and morphology, the protection with the high dose was complete, and regarding sperm mobility and viability, the protection was more than 74%. In the comet assay, the highest dose showed a reduction of 92.5% in the damage induced by CC, and regarding the number of micronuclei in the spermatids, the reduction was 83.3%. In the oxidative evaluation, regarding sperm lipoperoxidation, the improvement was complete with the high dose, and in the ABTS.+ test, the improvement in the response to the BC high dose was 26.3%. Regarding testicular lipoperoxidation and protein oxidation, the protective effects of the high BC dose were 87.6% and 89.9%, respectively. We also found that BC protected against the histological and morphometric alterations induced by CC. Therefore, our study clearly demonstrates the beneficial, chemopreventive effect of BC against the mouse sperm and testicular alterations induced by CC.
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Cloreto de Cádmio , Testículo , Animais , Antioxidantes/farmacologia , Cádmio/toxicidade , Cloreto de Cádmio/toxicidade , Masculino , Camundongos , Estresse Oxidativo , Sesquiterpenos Policíclicos , EspermatozoidesRESUMO
The present study aimed to determine the effectiveness of sclerotherapy using NBCA (Histoacryl Blue®; B. Braun, Melgungen, Germany), with or without hydrodissection, for the treatment of simple renal cysts. Materials and Methods: Patients who presented to an interventional radiology clinic for the diagnosis of symptomatic renal cysts which had previously been identified at an outpatient clinic were selected for inclusion in this study. A total of 28 patients were randomly divided into 2 groups, based on whether or not they underwent hydrodissection along with ultrasound-guided NBCA-based sclerotherapy. Sonographs were performed at 0, 7, and 180 days post-procedure to record the residual volume of the renal cysts and to determine the efficacy of the procedure. Results: A total of 32 cysts in 28 patients were treated with sclerotherapy, 18 (64%) females and 10 (36%) males. The average age of the patients was 61.8 years (range: 33-89 years). All patients reported an improvement in symptoms associated with the existing renal cysts at 7 and 180 days post-procedure, and at 7 days post-procedure a statistically significant reduction in cyst volume was observed (all patients: 96.8%; group A: 96%; group B: 97.6%). The reduced cyst volume was still observed 180 days post-procedure (all patients: 98.6%; group A: 98.2%; group B: 98.9%). There was no significant difference between the two treatment groups. Conclusion: There is a significant and persistent reduction in the volume of renal cysts, in addition to an improvement of the associated symptoms, after treatment with NBCA-based sclerotherapy, with or without hydrodissection.
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Pomegranate (Punica granatum L.) is a fruit used extensively in traditional medicine by ancient and modern cultures. Different parts of the tree and fruit, such as leaf, peel, pericarp, aril, seed, and juice contain considerable amounts of phenolic compounds with high antioxidant activities. To improve its storability, pomegranate juice was microencapsulated by spray drying. The present study evaluated microencapsulated pomegranate juice (MPJ) for toxic effects in Wistar rats and CD-1 mice to determine if MPJ can be considered safe for human consumption and used as a nutraceutical. No deaths or deleterious effects occurred when high doses of 5000 mg/kg were orally administered in rats for 14 days, indicating an absence of subacute toxicity. Similarly, 3000 mg/kg MPJ administered to CD-1 mice for 90 days did not show subchronic toxicity. In fact, MPJ resulted in lowered weight gain in both rats and mice. Cytotoxic and microbiological analyses of MPJ were also performed. MPJ did not cause any cytotoxicity in epithelial cell culture as tested using the Alamar blue assay. Additionally, histopathological analysis of kidney and liver corroborated the absence of toxicity in CD-1 mice. The microbial load of the MPJ was low, and no pathogenic bacteria were present. In conclusion, the results reported here show that high doses of MPJ are apparently innocuous in rats and mice for the 14 and 90 days investigated, respectively. Although preliminary, our results suggest that MPJ may be safe to ingest and may even have beneficial effects in reducing weight gain.
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Asthma is a chronic disease whose main anatomical-functional alterations are grouped into obstruction, nonspecific bronchial hyperreactivity, inflammation and airway remodeling. Currently, the Global Initiative of Asthma 2020 (GINA 2020) suggests classifying it into intermittent cases, slightly persistent, moderately persistent and severely persistent, thus determining the correct guidelines for its therapy. In general, the drugs used for its management are divided into two groups, those with a potential bronchodilator and the controlling agents of inflammation. However, asthmatic treatments continue to evolve, and notable advances have been made possible in biological therapy with monoclonal antibodies and in the relationship between this disease and oxidative stress. This opens a new path to dietary and herbal strategies and the use of antioxidants as a possible therapy that supports conventional pharmacological treatments and reduces their doses and/or adverse effects. This review compiles information from different published research on risk factors, pathophysiology, classification, diagnosis and the main treatments; likewise, it synthesizes the current evidence of herbal medicine for its control. Studies on integrative medicine (IM) therapies for asthmatic control are critically reviewed. An integrative approach to the prevention and management of asthma warrants consideration in clinical practice. The intention is to encourage health professionals and scientists to expand the horizons of basic and clinical research (preclinical, clinical and integrative medicine) on asthma control.
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Asma/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antioxidantes/uso terapêutico , Asma/classificação , Asma/diagnóstico , Asma/fisiopatologia , Broncodilatadores/uso terapêutico , Humanos , Estresse Oxidativo , Preparações de Plantas/uso terapêutico , Fatores de RiscoRESUMO
Roselle (Hibiscus sabdariffa L.), also known as jamaica in Spanish, is a perennial plant that grows in tropical and subtropical regions, including China, Egypt, Indonesia, Mexico, Nigeria, Thailand, and Saudi Arabia. It has a long history of uses, mainly focused on culinary, botanical, floral, cosmetic, and medicinal uses. The latter being of great impact due to the diuretic, choleretic, analgesic, antitussive, antihypertensive, antimicrobial, immunomodulatory, hepatoprotective, antioxidant, and anti-cancer effects. These therapeutic properties have been attributed to the bioactive compounds of the plant, mainly phenolic acids, flavonoids, anthocyanins, and organic acids (citric, hydroxycitric, hibiscus, tartaric, malic, and ascorbic). Most literature reviews and meta-analyses on the therapeutic potential of Hibiscus sabdariffa L. (Hs) compounds have not adequately addressed the contributions of its organic acids present in the Hs extracts. This review compiles information from published research (in vitro, in vivo, and clinical studies) on demonstrated pharmacological properties of organic acids found in Hs. The intent is to encourage and aid researchers to expand their studies on the pharmacologic and therapeutic effects of Hs to include assessments of the organic acid components.
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Salmonella enterica serotype Typhimurium is a bacterium that causes gastroenteritis and diarrhea in humans. The genome of S. Typhimurium codes for diverse virulence factors, among which are the toxin-antitoxin (TA) systems. SehAB is a type II TA, where SehA is the toxin and SehB is the antitoxin. It was previously reported that the absence of the SehB antitoxin affects the growth of S. Typhimurium. In addition, the SehB antitoxin can interact directly with the SehA toxin neutralizing its toxic effect as well as repressing its own expression. We identified conserved residues on SehB homologous proteins. Point mutations were introduced at both N- and C-terminal of SehB antitoxin to analyze the effect of these changes on its transcription repressor function, on its ability to form homodimers and on the virulence of S. Typhimurium. All changes in amino acid residues at both the N- and C-terminal affected the repressor function of SehB antitoxin and they were required for DNA-binding activity. Mutations in the amino acid residues at the N-terminal showed a lower capacity for homodimer formation of the SehB protein. However, none of the SehB point mutants were affected in the interaction with the SehA toxin. In terms of virulence, the eight single-amino acid mutations were attenuated for virulence in the mouse model. In agreement with our results, the eight amino acid residues of SehB antitoxin were required for its repressor activity, affecting both homodimerization and DNA-binding activity, supporting the notion that both activities of SehB antitoxin are required to confer virulence to Salmonella enterica.
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Diabetes mellitus is the most common chronic disease worldwide that causes numerous complications, including male infertility. The prevalence of DM is 451 million people and estimated that would increase to 693 million in 2045. Fluorosis caused by drinking water contaminated with inorganic fluoride is a public health problem in many areas around the world. Previous studies have shown that fluoride exposure damages the male reproductive function. This study aimed to evaluate the fluoride sub-chronic exposure on the spermatozoa function in streptozotocin (STZ)-induced diabetic mice. After confirming diabetes by measuring blood glucose levels, the male mice received 45.2 ppm of fluoride added or deionized water. We evaluated several parameters in diabetic mice exposed to fluoride: standard quality analysis, the mitochondrial transmembrane potential (ψm), the caspase activity in spermatozoa, urinary fluoride excretion, and histological evaluation in the testes. After 60 days of fluoride-exposure, diabetic mice, significantly decreased sperm quality (motility, viability, and concentration). Spermatozoa from fluoride-exposure in diabetic mice presented a significant decrease in ψm and a significant increase in activity caspase 3/7. Urinary fluoride excretion was decreased in diabetic mice exposed to fluoride. Subchronic fluoride exposure of mice with STZ-induced diabetes aggravated testicular damage and the spermatozoa function.
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Traditional Medicine/Complementary and Alternative Medicine is a practice that incorporates medicine based on plants, animals, and minerals for diagnosing, treating, and preventing certain diseases, including chronic degenerative diseases such as obesity, diabetes, hypertension, atherosclerosis, and cancer. Different factors generate its continued acceptance, highlighting its diversity, easy access, low cost, and the presence of relatively few adverse effects and, importantly, a high possibility of discovering antigenotoxic agents. In this regard, it is known that the use of different antigenotoxic agents is an efficient alternative to preventing human cancer and that, in general, these can act by means of a combination of various mechanisms of action and against one or various mutagens and/or carcinogens. Therefore, it is relevant to confirm its usefulness, efficacy, and its spectrum of action through different assays. With this in mind, the present manuscript has as its objective the compilation of different investigations carried out with garlic that have demonstrated its genoprotective capacity, and that have been evaluated by means of five of the most outstanding tests (Ames test, sister chromatid exchange, chromosomal aberrations, micronucleus, and comet assay). Thus, we intend to provide information and bibliographic support to investigators in order for them to broaden their studies on the antigenotoxic spectrum of action of this perennial plant.
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Cancer is one of the leading causes of death worldwide. The agents capable of causing damage to genetic material are known as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens, or teratogens. Genotoxins are also involved in the pathogenesis of several chronic degenerative diseases, including hepatic, neurodegenerative, and cardiovascular disorders; diabetes; arthritis; cancer; chronic inflammation; and ageing. In recent decades, researchers have found novel bioactive phytocompounds able to counteract the effects of physical and chemical mutagens. Several studies have shown the antigenotoxic potential of different fruits and plants (Part 1). In this review (Part 2), we present a research overview conducted on some plants and vegetables (spirulina, broccoli, chamomile, cocoa, ginger, laurel, marigold, roselle, and rosemary), which are frequently consumed by humans. In addition, an analysis of some phytochemicals extracted from those vegetables and the analysis of a resin (propolis),whose antigenotoxic power has been demonstrated in various tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus, and comet assay, was also performed.
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Antimutagênicos , Produtos Biológicos , Preparações de Plantas , Animais , Linhagem Celular , Ensaio Cometa , Dano ao DNA , Humanos , Camundongos , Compostos Fitoquímicos , Própole , Spirulina , VerdurasRESUMO
High-density lipoproteins (HDL) comprise a heterogeneous family of lipoprotein particles divided into subclasses that are determined by density, size and surface charge as well as protein composition. Epidemiological studies have suggested an inverse correlation between High-density lipoprotein-cholesterol (HDL-C) levels and the risk of cardiovascular diseases and atherosclerosis. HDLs promote reverse cholesterol transport (RCT) and have several atheroprotective functions such as anti-inflammation, anti-thrombosis, and anti-oxidation. HDLs are considered to be atheroprotective because they are associated in serum with paraoxonases (PONs) which protect HDL from oxidation. Polyphenol consumption reduces the risk of chronic diseases in humans. Polyphenols increase the binding of HDL to PON1, increasing the catalytic activity of PON1. This review summarizes the evidence currently available regarding pharmacological and alternative treatments aimed at improving the functionality of HDL-C. Information on the effectiveness of the treatments has contributed to the understanding of the molecular mechanisms that regulate plasma levels of HDL-C, thereby promoting the development of more effective treatment of cardiovascular diseases. For that purpose, Scopus and Medline databases were searched to identify the publications investigating the impact of current therapies focused on high-density lipoproteins.
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Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Hipolipemiantes/uso terapêutico , Lipoproteínas HDL/metabolismo , Animais , Biomarcadores , Doenças Cardiovasculares/etiologia , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipoproteínas/classificação , Lipoproteínas/metabolismo , Lipoproteínas HDL/sangue , Oxirredução/efeitos dos fármacosRESUMO
CONTEXT: Heliopsis longipes (A. Gray) Blake (Asteraceae), a plant native to Mexico, is used in traditional medicine as analgesic and microbicide. The main component in the H. longipes ethanolic extract (HLEE) is affinin, as determined by HPLC/UV-visible and NMR measurement. To date, there is no documented evidence on the spermicidal activity of this extract. OBJECTIVE: The objective of this study was to assess in vitro the effectiveness of HLEE as spermicide. MATERIALS AND METHODS: The spermicidal activity of HLEE was evaluated by the Sander-Cramer assay. Spermatozoa were incubated for 20 s with HLEE in concentrations ranging from 75 to 2000 µg/mL to determine the minimum effective concentration (MEC) value. The 50% effective concentration (EC50) of HLEE was estimated by assaying serial dilutions from the MEC. Additionally, sperms were incubated with 125, 250, or 500 µg/mL of HLEE to evaluate the viability and the integrity of sperm membrane. Lipid peroxidation was assessed by the thiobarbituric acid reactive substances assay. RESULTS: HLEE caused an inhibition of 100% in spermatozoa motility at a MEC value of 2000 µg/mL; the EC50 value was 125 µg/mL. Additionally, exposure to HLEE at 125, 250, or 500 µg/mL for 30 min decreased sperm viability to 27%, 8%, and 2% of the control value, respectively, and significantly increased the percentage of sperms with structurally disorganized membrane. HLEE also increased significantly the level of lipid peroxidation in sperms with respect to controls. DISCUSSION AND CONCLUSION: The results demonstrate the spermicidal activity of HLEE in vitro and suggest that this action is caused by oxidative damage and alterations in the spermatozoal membrane.
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Asteraceae/química , Etanol/química , Extratos Vegetais/farmacologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermicidas/farmacologia , Espermatozoides/efeitos dos fármacos , Animais , Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Técnicas In Vitro , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Espermicidas/isolamento & purificação , Espermatozoides/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Aflatoxins are a group of naturally-occurring carcinogens that are known to contaminate different human and animal foodstuffs. Aflatoxin B1 (AFB1) is the most genotoxic hepatocarcinogenic compound of all of the aflatoxins. In this report, we explore the capacity of ß-D-glucan (Glu) to reduce the DNA damage induced by AFB1 in mouse hepatocytes. For this purpose, we applied the comet assay to groups of animals that were first administered Glu in three doses (100, 400 and 700 mg/kg bw, respectively) and, 20 min later, 1.0 mg/kg of AFB1. Liver cells were obtained at 4, 10 and 16 h after the chemical administration and examined. The results showed no protection of the damage induced by AFB1 with the low dose of the polysaccharide, but they did reveal antigenotoxic activity exerted by the two high doses. In addition, we induced a co-crystallization between both compounds, determined their fusion points and analyzed the molecules by UV spectroscopy. The data suggested the formation of a supramolecular complex between AFB1 and ß-D-glucan.
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Aflatoxina B1/toxicidade , Anticarcinógenos/farmacologia , Carcinógenos/toxicidade , Quebras de DNA/efeitos dos fármacos , beta-Glucanas/farmacologia , Aflatoxina B1/química , Animais , Anticarcinógenos/química , Carcinógenos/química , Ensaio Cometa , Cristalização , Hepatócitos/efeitos dos fármacos , Masculino , Camundongos , Proteoglicanas , beta-Glucanas/químicaRESUMO
Resveratrol (RVT) is a polyphenolic compound found mainly in the grape and attributed with various pharmacological properties, among them their antioxidant activity. In the present study, we assess the antioxidant activity of resveratrol on oxidative damage induced by ferrous iron/ascorbate (100 µM/150 µM) in sperm of CD1+ mice. We evaluated several parameters in spermatozoa treated with or without resveratrol: (i) sperm quality analysis; (ii) mitochondrial transmembrane potential (Δѱm); (iii) ROS generation; (iv) superoxide dismutase (SOD) activity; (v) glutathione peroxidase (GPX) activity; (vi) lipid peroxidation; (vii) and in vitro fertilization (IVF) capability. Spermatozoa treated with RVT (15 µg/mL) before ferrous iron/ascorbate treatment exhibited: a significant increase in motility (8-fold), a significant increase in viability (2-fold), a significant increase in Δѱm (1.15-fold), accompanied with a significant decrease in the generation of ROS (4.96-fold), a significant decrease in GPX activity (1.32-fold), and a significant decrease in lipid peroxidation concentration (10.29-fold) relative to spermatozoa treated with ferrous iron/ascorbate; however, no changes in SOD activity were observed. Finally, spermatozoa treated with RVT before ferrous iron/ascorbate treatment showed a significant increase in oocyte fertilization (1.2-fold), relative to spermatozoa treated with ferrous iron/ascorbate. These results suggest that RVT possesses antioxidant properties that may prevent the deleterious effects produced by oxidative damage on spermatozoa, resulting in the maintenance of fertility.
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Ácido Ascórbico/efeitos adversos , Biomarcadores/sangue , Estresse Oxidativo/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Antioxidantes/farmacologia , Feminino , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Resveratrol , Espermatozoides/metabolismo , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
There is evidence that systemic sulfonylureas block diclofenac-induced antinociception in normal rat, suggesting that diclofenac activates ATP-sensitive K(+) channels. However, there is no evidence for the systemic interaction between different non-steroidal anti-inflammatory drugs (NSAIDs) and sulfonylureas in streptozotocin (STZ)-diabetic rats. Therefore, this work was undertaken to determine whether two sulfonylureas, glibenclamide and glipizide, have any effect on the systemic antinociception that is induced by diclofenac (30 mg/kg), lumiracoxib (56 mg/kg), meloxicam (30 mg/kg), metamizol (56 mg/kg) and indomethacin (30 mg/kg) using the non-diabetic and STZ-diabetic rat formalin test. Systemic injections of NSAIDs produced dose-dependent antinociception during the second phase of the test in both non-diabetic and STZ-diabetic rats. Systemic pretreatment with glibenclamide (10 mg/kg) and glipizide (10 mg/kg) blocked diclofenac-induced systemic antinociception in the second phase of the test (P<0.05) in both non-diabetic and STZ-diabetic rats. In contrast, pretreatment with glibenclamide or glipizide did not block lumiracoxib-, meloxicam-, metamizol-, and indomethacin-induced systemic antinociception (P>0.05) in both groups. Results showed that systemic NSAIDs are able to produce antinociception in STZ-diabetic rats. Likewise, data suggest that diclofenac, but not other NSAIDs, activated K(+) channels to induce its systemic antinociceptive effect in the non-diabetic and STZ-diabetic rat formalin test.
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Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Canais KATP/agonistas , Canais KATP/fisiologia , Medição da Dor/efeitos dos fármacos , Analgésicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Diabetes Mellitus Experimental/metabolismo , Masculino , Medição da Dor/métodos , Ratos , Ratos WistarRESUMO
There are few reports that demonstrate the antigenotoxic potential of cranberries. Although the types of berry fruits consumed worldwide are many, this paper focuses on cranberries that are commonly consumed in Mexico (Vaccinium macrocarpon species). The purpose of the present study is to determine whether cranberry ethanolic extract (CEE) can prevent the DNA damage produced by benzo[a]pyrene (B[a]P) using an in vivo mouse peripheral blood micronucleus assay. The experimental groups were organized as follows: a negative control group (without treatment), a positive group treated with B[a]P (200 mg/kg), a group administered with 800 mg/kg of CEE, and three groups treated with B[a]P and CEE (200, 400, and 800 mg/kg) respectively. The CEE and benzo[a]pyrene were administered orally for a week, on a daily basis. During this period the body weight, the feed intake, and the determination of antigenotoxic potential were quantified. At the end of this period, we continued with the same determinations for one week more (recovery period) but anymore administration of the substances. The animals treated with B[a]P showed a weight increase after the first week of administration. The same phenomenon was observed in the lots combined with B[a]P and CEE (low and medium doses). The dose of 800 mg/kg of CEE showed similar values to the control group at the end of the treatment period. In the second part of the assay, when the substances were not administered, these experimental groups regained their normal weight. The dose of CEE (800 mg/kg) was not genotoxic nor cytotoxic. On the contrary, the B[a]P increases the frequency of micronucleated normochromatic erythrocytes (MNNE) and reduces the rate of polychromatic erythrocytes (PE) at the end of the treatment period. With respect to the combined lots, a significant decrease in the MN rate was observed from the sixth to the eighth day of treatment with the two high doses applied; the highest protection (60%) was obtained with 800 mg/kg of CEE. The same dose showed an anticytotoxic effect which corresponded to an improvement of 62.5% in relation to the animals administered with the B[a]P. In the second period, all groups reached values that have been seen in the control group animals. Our results suggest that the inhibition of clastogenicity of the cranberry ethanolic extract against B[a]P is related to the antioxidant capacity of the combination of phytochemicals present in its chemical composition.
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Benzo(a)pireno/toxicidade , Dano ao DNA/efeitos dos fármacos , Extratos Vegetais/farmacologia , Vaccinium macrocarpon/química , Animais , Antioxidantes/farmacologia , Relação Dose-Resposta a Droga , Masculino , Camundongos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Testes para MicronúcleosRESUMO
Fluorosis, caused by drinking water contaminated with inorganic fluoride, is a public health problem in many areas around the world. The aim of this study was to evaluate oxidative stress in spermatozoa caused by fluoride and NADPH oxidase in relationship to fluoride. Four experimental groups of male Wistar rats were administered with deionized water, NaF, at a dose equivalent to 5 mg fluoride kg⻹ per 24 h, NaF plus 20 mg kg⻹ per 24 h α-tocopherol, or α-tocopherol alone for 60 days. We evaluated several spermatozoa parameters in the four groups: standard quality analysis, superoxide dismutase (SOD) activity, the generation of reactive oxygen species (ROS), NADPH oxidase activity, TBARS formation, ultrastructural analyses of spermatozoa using transmission electron microscopy and in vitro fertilization (IVF) capacity. After 60 days of treatment, urinary excretion of fluoride was not modified by α-tocopherol. Spermatozoa from fluoride-treated rats exhibited a significant increase in the generation of ROS, accompanied by a significant increase in NADPH oxidase activity. The increase in ROS generation was significantly diminished by diphenylene iodonium, an inhibitor of NADPH oxidase activity. In contrast, a decrease in the generation of ROS, an increase in SOD activity and the prevention of TBARS formation process were observed in spermatozoa of rats exposed to fluoride plus α-tocopherol. Finally, α-tocopherol treatment prevented the IVF incapacity observed in the spermatozoa from fluoride-treated rats. These results suggest that NADPH oxidase participates in the oxidative stress damage caused by subchronic exposure to fluoride.
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Antioxidantes/farmacologia , Fluoretos/toxicidade , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , alfa-Tocoferol/farmacologia , Animais , Masculino , Microscopia Eletrônica de Transmissão , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Espermatozoides/patologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Testes de Toxicidade SubcrônicaRESUMO
Pharmacovigilance is the permanent collection and assessment of the safety data of drugs in the interest of precise knowledge of the safety profile. We monitored notifications of suspected adverse reactions (AR) produced by psychoactive medications (ARPM) in a Psychiatry Hospital, during a 4-month period. Yellow cards for adverse reaction reporting were distributed to the medical personal at the Hospital Psiquiátrico Villa Ocaranza, Pachuca Hidalgo, Mexico. For each notification, the ARPM was analyzed in order to verify causality. One hundred twelve hospitalized patients entered the study (44 male and 68 female). The mean +/- SD age of the patients was 46 +/- 4.5 years. The major diagnoses found were: schizophrenia (35.7%), severe mental retardation (17 %), moderate mental retardation (MMR)/epilepsy (12.5%), MMR (8.03%), and others (26.7%). During the study there were 721 therapeutic regimens prescribed to patients on psychiatric service. Patients were receiving an average of 5.3 +/- 1.1 (range 4 to 8) psychiatric medications. The psychiatrists reported only 5 ARPMs in five patients (prevalence: 4.46%). Among the drugs involved were neuroleptics (47.8%), antiepileptic (39.1%), and others (13.04%). The organs and systems affected by the ARs were the central nervous system, skin, endocrinological and gastrointestinal. A causal association between the medication and the AR were classified as probable in three cases, as possible in one case, as doubtful in one case and as definite in no case.
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Farmacovigilância , Psicotrópicos/uso terapêutico , Adulto , Feminino , Hospitais Psiquiátricos , Humanos , Masculino , México , Pessoa de Meia-IdadeRESUMO
Tissue degeneration, infection, inflammation, cancer, trauma, surgery and limb fractures all produce pain. Each of these physiological abnormalities requires a therapeutic approach different from the last. In acute pain, caused by fracture, several classes of analgesics have been utilized. These basic remedies for analgesia, however, are still confined to a small number of medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), local anesthetics and opioids. In addition, most of these drugs have side effects, limiting their use in clinical practice. The purpose of this study was to compare the efficacy of three NSAIDs to relief acute pain caused by ankle fracture. Sixty subjects with ankle fracture were randomized to receive ketorolac, diclofenac, or etoricoxib, every 12 hours in a prospective, double-blind study. Forty-nine patients completed the study. The subjects' assessments of ankle pain on the visual analog scale and a Likert scale showed a significant reduction from baseline over 24 hr, regardless the treatment group. All treatments showed a similar profile in pain reduction. Etoricoxib, diclofenac and ketorolac twice daily are a rapid and effective treatment for acute pain. All the regimens were well tolerated in this study.