RESUMEN
BACKGROUND: Mitochondrial dysfunction and increase in reactive oxygen species during diabetes can lead to pathological consequences in kidneys. The present study was aimed to investigate the effect of Phellinus rimosus in the streptozotocin (STZ)-induced diabetic rat renal mitochondria and the possible mechanism of protection. METHODS: Phellinus rimosus (50 and 250 mg/kg, p.o) was treated after inducing diabetes by STZ (45 mg/kg, i.p) in rats. The serum samples were subjected to creatinine and urea estimation. Mitochondrial antioxidant status such as mitochondrial superoxide dismutase, glutathione peroxidase, and reduced glutathione; adenosine triphosphate level; and lipid peroxidation were measured. The activities of Krebs cycle enzymes such as isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase as well as mitochondrial complexes I, III, and IV in kidney mitochondria were also determined. RESULTS: Administration of P. rimosus (250 mg/kg b.wt) once daily for 30 days, significantly (p<0.05) enhanced the activities of Krebs cycle dehydrogenases, mitochondrial electron transport chain complexes, and ATP level. Further, P. rimosus had significantly protected the renal mitochondrial antioxidant status and lipid peroxidation. CONCLUSIONS: The results of the study concluded that by limiting the extent of renal mitochondrial damage in the hyperglycemic state, P. rimosus alleviated nephrotoxicity.
Asunto(s)
Agaricales/química , Productos Biológicos/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Riñón/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Creatinina/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Riñón/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Estreptozocina/farmacología , Superóxido Dismutasa/metabolismoRESUMEN
Patients with the risk for atherosclerotic disease will be targeted to reduce the existing hyperlipidemia. The hypolipidemic activity of Phellinus rimosus was studied using triton WR-1339 and high cholesterol diet (HCD) induced models. The triton induced elevated lipid profile was attenuated by P. rimosus or standard drug atorvastatin. Similarly, administration of P. rimosus along with HCD significantly decline serum triglyceride, total cholesterol, low-density lipoprotein, with elevating the high-density lipoprotein. Thiobarbituric acid reacting substances in heart and liver significantly decreased; where as activity of enzymatic antioxidants and level of reduced glutathione were significantly increased. In both models, P. rimosus extract showed a significant ameliorative effect on the elevated atherogenic index as well as LDL/HDL-C ratio. The hypolipidemic activity of P. rimosus can be ascribed to its inhibitory effect on the liver HMG CoA reductase activity. The results suggest the possible therapeutic potential of this fungus as hypolipidemic agent.
Asunto(s)
Basidiomycota , Mezclas Complejas/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Mezclas Complejas/farmacología , Dieta Alta en Grasa , Hidroximetilglutaril-CoA Reductasas/metabolismo , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hiperlipidemias/etiología , Hiperlipidemias/metabolismo , Hipolipemiantes/farmacología , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Miocardio/metabolismo , Polietilenglicoles , Ratas Wistar , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Acetaminophen (APAP) is known to induce liver mitochondrial dysfunction leading to acute hepatotoxicity. Effect of DL-α-lipoic acid (LA) and α-tocopherol (α-Toc) against the APAP-induced liver mitochondrial damage was evaluated in rats. LA (100 mg/kg, p.o.) and α-Toc (100 mg/kg, p.o.) were given once daily for 15 d, prior to the APAP administration (3 g/kg, p.o). Hepatic damage was confirmed by determining the activities of serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase and alkaline phosphatase, 4 h after the single dose of APAP. To assess the mitochondrial damage, the activities of antioxidant enzymes, Krebs' cycle dehydrogenases and mitochondrial electron transport chain complexes, and levels of reactive oxygen species (ROS), reduced glutathione, lipid peroxidation (malondialdehyde, MDA) as well as the mitochondrial membrane potential (Δψmt) were evaluated. The activities of mitochondrial enzymes and Δψmt were significantly (p < 0.01) decreased and the level of ROS and MDA were significantly (p < 0.01) increased due to APAP challenge. LA and α-Toc treatment significantly enhanced the activities of mitochondrial enzymes and Δψmt than that of control group; whereas the levels of ROS and MDA were decreased. The results of the study concluded that the liver damage induced by APAP was significantly ameliorated by LA and α-Toc. LA showed more protection than that of α-Toc. The protection can be partially ascribed to their mitochondrial protective effects through their antioxidant activity which could decrease the level of ROS and by direct enhancement of Δψmt.
Asunto(s)
Acetaminofén/toxicidad , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ácido Tióctico/farmacología , alfa-Tocoferol/farmacología , Animales , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Decreased mitochondrial function has been suggested to be one of the important pathological events in isoproterenol (ISO)-induced cardiotoxicity. In this communication, we have evaluated the protective effect of Ganoderma lucidum against ISO induced cardiac toxicity and mitochondrial dysfunction. METHODS: Cardiac toxicity was assessed by determining the activities of creatine kinase (CK) and lactate dehydrogenases (LDH) after subcutaneous injection of ISO (85 mg/kg) at an interval of 24h for 2 days. The animals were sacrificed 24h after last ISO administration. G. lucidum (100 and 250 mg/kg, p.o.) was given to the rats once daily for 15 days prior to the ISO challenge. Similarly, α-Tocopherol (100mg/kg, p.o) was kept as the standard. To assess the extent of cardiac mitochondrial damage, the activities of Krebs cycle dehydrogenases and mitochondrial complexes I, II, III, and IV as well as the level of ROS and mitochondrial membrane potential (ΔΨmt) were evaluated. RESULTS: Administration of G. lucidum and α-tocopherol significantly protected the elevated activities of CK and LDH. Further, the activities of mitochondrial enzymes and the level of ΔΨmt were significantly enhanced and the level of ROS was significantly declined in the G. lucidum and α-tocopherol treatments. CONCLUSION: The present study concluded that the cardiac mitochondrial enzymes are markedly declined by the ISO challenge and the administration G. lucidum and α-Tocopherol significantly protected mitochondria by preventing the decline of antioxidant status and ΔΨmt or by directly scavenging the free radicals.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Polisacáridos Fúngicos/uso terapéutico , Isoproterenol/toxicidad , Mitocondrias Cardíacas/enzimología , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/enzimología , Reishi/fisiología , Animales , Antioxidantes/metabolismo , Ciclo del Ácido Cítrico/efectos de los fármacos , Ciclo del Ácido Cítrico/fisiología , Creatina Quinasa/metabolismo , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Transporte de Electrón/efectos de los fármacos , Transporte de Electrón/fisiología , Activación Enzimática/efectos de los fármacos , Activación Enzimática/fisiología , Depuradores de Radicales Libres/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Masculino , Mitocondrias Cardíacas/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Mutations are one of the important factors contributing to oncogenesis. Somatic mutations have been detected in oncogenes and tumor suppressor genes in various types of cancers. In vitro antimutagenic activity of ethyl acetate extract of macro fungus, Phellinus rimosus was evaluated by Ames' mutagenicity assay. The effect was evaluated against the direct acting mutagens (sodium azide, N-methyl-N'-nitro-N-nitrosoguanidine, doxorubicin and 4-nitro-o-phenylenediamine) and mutagen needing activation (2-acetyl aminofluorine, and benzo[a]pyrene). The extract was significantly (p<0.05) and dose dependently effective against direct acting mutagens and mutagen needing activation. Among the antimutagenic activity against directly acting mutagens, effect was found to be highest against doxorubicin-induced mutation. The antimutagenic effect of the extract against indirect acting mutagen in the presence of mammalian metabolic activation system was also found to be significant (p<0.01). The background bacterial growth and number of revertant colonies in the extract alone treated plate with or with out metabolic activator was almost same as that of spontaneous revertants. This indicated the non-toxic nature of the extract. The effect was partially ascribed to the antioxidant activity. The results of the study suggest the possible antitumor mechanisms of P. rimosus.
Asunto(s)
Antimutagênicos/farmacología , Basidiomycota/química , Animales , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Pruebas de Mutagenicidad/métodos , Mutágenos/toxicidad , Mutación/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genéticaRESUMEN
Palladium alpha-lipoic acid formulation--'POLY-MVA' is found to enhance the activities of Krebs cycle dehydrogenases and respiratory complexes in the heart of aged rat. In this study, we aimed to evaluate the effect of POLY-MVA on the activities of antioxidant status in the heart mitochondria of aged rat. We determined the activities of manganese-superoxide dismutase (Mn SOD), catalase (CAT), glutathione peroxidase (GPx), and level of reduced GSH and lipid peroxidation in the heart mitochondria of aged rats, after administering POLY-MVA (0.05 ml/kg; equivalent to 0.38 mg complexed alpha-lipoic acid/kg) orally once daily for 30 days. DL-alpha-lipoic acid (0.38 mg/kg, p.o) treated for 30 days was kept as the positive control. We found that the antioxidant in the aged control was declined significantly than the young control. The formulation significantly (p<0.05) enhanced the activity of CAT and GPx compared to the aged control. The level of GSH was also significantly improved and the level of lipid peroxidation was decreased significantly (p<0.05) by POLY-MVA. The results indicate that POLY-MVA is effective to protect the age-linked decline of myocardial mitochondrial antioxidant status. The findings suggest the use of this formulation against myocardial aging.
Asunto(s)
Envejecimiento/fisiología , Antioxidantes/metabolismo , Antioxidantes/farmacología , Mitocondrias Cardíacas/efectos de los fármacos , Miocardio/metabolismo , Paladio/farmacología , Ácido Tióctico/farmacología , Animales , Catalasa/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Técnicas In Vitro , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND & AIMS: Post-mitotic cells such as brain and heart cells are particularly vulnerable to oxidative damages during ageing. In this study, we evaluated the effect of Ganoderma lucidum on the antioxidant status in the mitochondria of heart and brain of aged mice. METHODS: The effect was evaluated by estimating the activities of manganese-superoxide dismutase (Mn SOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and catalase (CAT) as well as levels of reduced glutathione (GSH), lipid peroxidation, advanced oxidation protein products (AOPP) and reactive oxygen species (ROS) in the heart and brain mitochondria of aged mice after oral administration of ethanolic extract of G. lucidum (50 and 250mg/kg), once daily for 15 days. The effect was compared with that of aged and young control animals. dl-alpha-lipoic acid (100mg/kg) was taken as the positive control. RESULTS: Administration of G. lucidum extract significantly (p<0.05) elevated the levels of GSH as well as activities of Mn SOD, GPx, and GST and decreased significantly (p<0.05) the levels of lipid peroxidation, AOPP and ROS. CONCLUSION: G. lucidum administration could improve the age-related decline of antioxidant status which was partly ascribed to free radical scavenging activity.
Asunto(s)
Envejecimiento/metabolismo , Antioxidantes/farmacología , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Reishi/química , Envejecimiento/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Etnofarmacología , Glutatión Peroxidasa/metabolismo , Glutatión Transferasa/metabolismo , India , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Mitocondrias/enzimología , Mitocondrias/metabolismo , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/enzimología , Mitocondrias Cardíacas/metabolismo , Oxidación-Reducción/efectos de los fármacos , Proteínas/química , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Iron is an essential nutrient for a number of cellular activities. However, excess cellular iron can be toxic by producing reactive oxygen species (ROS) such as superoxide anion (O(2) (-)) and hydroxyl radical (HO(·)) that damage proteins, lipids and DNA. Mutagenic and genotoxic end products of lipid peroxidation can induce the decline of mitochondrial respiration and are associated with various human ailments including aging, neurodegenerative disorders, cancer etc. Zingiber officinale Roscoe (ginger) is a widely used spice around the world. The protective effect of aqueous ethanol extract of Z. officinale against ROS-induced in vitro lipid peroxidation and DNA damage was evaluated in this study. The lipid peroxidation was induced by hydroxyl radical generated from Fenton's reaction in rat liver and brain homogenates and mitochondrial fraction (isolated from rat liver). The DNA protection was evaluated using H(2)O(2)-induced changes in pBR-322 plasmid and Fenton reaction-induced DNA fragmentation in rat liver. The results indicated that Z. officinale significantly (P<0.001) protected the lipid peroxidation in all the tissue homogenate/mitochondria. The extract at 2 and 0.5 mg/ml could protect 92 % of the lipid peroxidation in brain homogenate and liver mitochondria respectively. The percent inhibition of lipid peroxidation at 1mg/ml of Z. officinale in the liver homogenate was 94 %. However, the extract could partially alleviate the DNA damage. The protective mechanism can be correlated to the radical scavenging property of Z. officinale. The results of the study suggest the possible nutraceutical role of Z. officinale against the oxidative stress induced human ailments.
RESUMEN
Age-related decline in the capacity to withstand stress, such as ischemia and reperfusion, results in congestive heart failure. Though the mechanisms underlying cardiac decay are not clear, age dependent somatic damages to mitochondrial DNA (mtDNA), loss of mitochondrial function, and a resultant increase in oxidative stress in heart muscle cells may be responsible for the increased risk for cardiovascular diseases. The effect of a safe nutritional supplement, POLY-MVA, containing the active ingredient palladium alpha-lipoic acid complex, was evaluated on the activities of the Krebs cycle enzymes such as isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase as well as mitochondrial complexes I, II, III, and IV in heart mitochondria of aged male albino rats of Wistar strain. Administration of 0.05 ml/kg of POLY-MVA (which is equivalent to 0.38 mg complexed alpha-lipoic acid/kg, p.o), once daily for 30 days, was significantly (p<0.05) effective to enhance the Krebs cycle dehydrogenases, and mitochondrial electron transport chain complexes. The unique electronic and redox properties of palladium alpha-lipoic acid complex appear to be a key to this physiological effectiveness. The results strongly suggest that this formulation might be effective to protect the aging associated risk of cardiovascular and neurodegenerative diseases.
Asunto(s)
Envejecimiento/fisiología , Ciclo del Ácido Cítrico/efectos de los fármacos , Corazón/efectos de los fármacos , Miocardio/enzimología , Oxidorreductasas/metabolismo , Paladio/farmacología , Ácido Tióctico/química , Animales , Química Farmacéutica , Masculino , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/enzimología , Paladio/química , Ratas , Ratas Wistar , Ácido Tióctico/farmacologíaRESUMEN
Higher doses of antioxidant vitamins C and E have been proved to be effective against cisplatin-induced nephrotoxicity in animals. However, the possible effective equivalent dose in human was found to be higher than that of the upper tolerable intake level (UL) for these vitamins. Hence, the current study was aimed to evaluate the protective effect of co-supplementation of single and multi doses of vitamins C and E against cisplatin-induced acute renal failure in mice. Single dose of vitamin C (500 mg/kg), vitamin E (500 mg/kg), and vitamin C plus vitamin E (250 mg/kg each) were administered orally 1 h prior to cisplatin (12 mg/kg, i.p) injection, whereas in a multidose study they were administered 1 h prior, and 24 and 48 h after the cisplatin injection. Serum urea and creatinine levels were estimated 72 h after the injection of cisplatin. Renal concentrations of glutathione (GSH) and malondialdehyde (MDA) were also determined. Co-supplementation of vitamins significantly protected the cisplatin-induced increased levels of serum urea, creatinine, renal MDA, and the declined renal GSH level. Administration of single and multi doses of vitamin C plus E (250 mg/kg each) rendered significant nephroprotection. Therefore, accounting for the rare side effect from high intake of vitamins C and E observation of this study indicates that a multidose combination therapy of these vitamins at their lower doses can be effective in protecting the cisplatin-induced renal damage. The protection is partially mediated through the antioxidant effect of the vitamins.
Asunto(s)
Lesión Renal Aguda/inducido químicamente , Antineoplásicos/toxicidad , Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Cisplatino/toxicidad , Vitamina E/farmacología , Lesión Renal Aguda/prevención & control , Animales , Ácido Ascórbico/administración & dosificación , Glutatión/análisis , Masculino , Malondialdehído/análisis , Ratones , Vitamina E/administración & dosificaciónRESUMEN
Aging is associated with increased oxidative damage at multiple cellular levels, decline in cellular energy production and enhanced free radical status. The effect of the medicinal mushroom, Ganoderma lucidum on the activities of tricarboxylic acid (Krebs) cycle enzymes and mitochondrial complexes I-IV of the electron transport chain in aged rats were investigated. The activity of Krebs cycle enzymes, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase as well as mitochondrial complexes I, II, III, and IV were determined in heart of aged male Wistar rats orally administrated with 70% ethanolic extract (50 and 250 mg/kg) of G. lucidum. DL-alpha-lipoic acid (100 mg/kg) was taken as the positive control. Administration of the G. lucidum, once daily for 15 days, was significantly (P < 0.05) effective to enhance the Krebs cycle dehydrogenases, and mitochondrial electron transport chain complex IV activities in aged rats. The profound activity of the extract can be correlated to the significant antioxidant property of G. lucidum. The results of the study revealed that G. lucidum is effective to ameliorate the age associated decline of cellular energy status.
Asunto(s)
Envejecimiento/fisiología , Medicamentos Herbarios Chinos/farmacología , Proteínas del Complejo de Cadena de Transporte de Electrón/metabolismo , Transporte de Electrón/efectos de los fármacos , Mitocondrias Cardíacas , Reishi/química , Animales , Humanos , Masculino , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/enzimología , Mitocondrias Cardíacas/metabolismo , Ratas , Ratas WistarRESUMEN
Dysfunction of the mitochondrial respiratory chain, being direct intracellular source of reactive oxygen species (ROS), is important in the pathogenesis of number of ageing associated human disorders. Effect of ethanol extract of Ganoderma lucidum on the activities of mitochondrial dehydrogenases; complex I and II of electron transport chain have been evaluated in the aged rat brain. Aged male Wistar rats were administered with ethanol extract of G. lucidum (50 and 250mg/kg, p.o) once daily for 15 days. Similarly DL-alpha-lipoic acid (100mg/kg, p.o) administered group was kept as the reference standard. Young and aged rats administered with water were kept as young and aged control, respectively. The effect of treatment was assessed by estimating the activities of succinate dehydrogenase (SDH), malate dehydrogenase (MDH), alpha-ketoglutarate dehydrogenase (alpha-KGDH), pyruvate dehydrogenase (PDH), complex I and II in the mitochondria of rat brain. Results of the study demonstrated that the extract of G. lucidum (50 and 250mg/kg) significantly (p<0.01) enhanced the activities of PDH, alpha-KGDH, SDH, complex I and II when compared to that of the aged control animals. The level of the lipid peroxidation was significantly lowered (p<0.01) in the G. lucidum treated group with respect to that of aged control. However, we could not find any statistically significant difference between the activities of enzymes in groups treated with 50 and 250mg/kg of G. lucidum. The activity exhibited by the extract of G. lucidum in the present study can be partially correlated to its antioxidant activity. The results of the study concluded that the extract of G. lucidum may effective to improve the function of mitochondria in aged rat brain, suggest its possible therapeutic application against ageing associated neurodegenerative diseases.
Asunto(s)
Envejecimiento/fisiología , Medicamentos Herbarios Chinos/farmacología , Proteínas del Complejo de Cadena de Transporte de Electrón/metabolismo , Transporte de Electrón/efectos de los fármacos , Mitocondrias/enzimología , Reishi/química , Animales , Antioxidantes/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Proteínas del Complejo de Cadena de Transporte de Electrón/efectos de los fármacos , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Mitocondrias/efectos de los fármacos , Oxidorreductasas/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/farmacologíaRESUMEN
Oxidative stress due to abnormal production of reactive oxygen species has been implicated in the nephrotoxicity induced by a commonly used anticancer antibiotic doxorubicin (DXN). The nephroprotective effect of aqueous ethanol extract of Zingiber officinale (200 and 400mg/kg, p.o) was evaluated against doxorubicin-induced (15mg/kg, i.p) acute renal damage in rat. Serum urea and creatinine levels were evaluated as the markers of renal failure. Renal antioxidant status such as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and level of reduced glutathione (GSH) were determined. Level of lipid peroxidation as equivalents of malondialdehyde (MDA), and glutathione-S-transferase (GST) activity were determined in the kidneys. Serum urea and creatinine levels were reduced in the Z. officinale (200 and 400mg/kg, p.o) plus DXN treated groups. The renal antioxidant enzymes activities such as SOD, CAT GPx, levels of GSH and GST activity were restored and that of MDA declined significantly (p<0.001) in the Z. officinale (400mg/kg) plus DXN treated group. The nephroprotection is mediated by preventing the DXN-induced decline of renal antioxidant status, and also by increasing the activity of GST.
Asunto(s)
Antibióticos Antineoplásicos/antagonistas & inhibidores , Antibióticos Antineoplásicos/toxicidad , Doxorrubicina/antagonistas & inhibidores , Doxorrubicina/toxicidad , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Zingiber officinale/química , Animales , Antioxidantes/metabolismo , Antioxidantes/uso terapéutico , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Femenino , Glutatión/metabolismo , Glutatión Transferasa/metabolismo , Riñón/enzimología , Riñón/patología , Pruebas de Función Renal , Malondialdehído/metabolismo , Extractos Vegetales/uso terapéutico , Ratas , Ratas Sprague-Dawley , Vitamina E/uso terapéuticoRESUMEN
1. Free radical-induced lipid peroxidation and changes in protein and nucleic acid structures can result in various human ailments, including ageing, neurodegenerative disorders and cancer. High body fat or dietary fat further enhances the free radical-mediated pathogenesis of various diseases. 2. In the present study, the in vitro anti-oxidant and DNA protective effects of the novel cardiovascular drug rosuvastatin were evaluated. Anti-oxidant activity was evaluated on the basis of inhibition of lipid peroxidation, scavenging of superoxide radical and the reduction of ferric ions (Fe(3+)). Inhibition of lipid peroxidation was determined using Fenton's reaction-induced lipid peroxidation in rat liver and brain homogenates and liver mitochondria. Superoxide radical-scavenging activity was evaluated by scavenging of the superoxide anion generated by photo illumination of riboflavin and Fe(3+)-reducing activity was determined by the ferric-reducing anti-oxidant power (FRAP) assay. DNA protection was evaluated according to changes in H(2)O(2)-induced pBR322 plasmid DNA and Fenton's reaction-induced-fragmentation of rat liver DNA. 3. The results indicate that rosuvastatin (1.5 or 2 mg/mL) is able to protect against lipid peroxidation. Furthermore, H(2)O(2)-induced changes in pBR322 plasmid DNA and fragmentation of hepatic DNA were alleviated by rosuvastatin. However, rosuvastatin did not show any superoxide anion-scavenging activity. The protective mechanism of rosuvastatin can be correlated with the reducing equivalent donating property or direct hydroxyl radical-scavenging activity of the drug. 4. The pleiotropic activities of rosuvastatin exhibited suggest its clinical advantages against oxidative stress-induced human ailments in addition to its widely using hypolipidaemic effect.
Asunto(s)
Antioxidantes/farmacología , Daño del ADN/efectos de los fármacos , Fluorobencenos/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Pirimidinas/farmacología , Sulfonamidas/farmacología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Peróxido de Hidrógeno , Peroxidación de Lípido/efectos de los fármacos , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Ratas , Rosuvastatina CálcicaRESUMEN
Chemoprevention represents a new intervention strategy to control some type of carcinogenesis especially in subjects at high risk for cancer development. Experimental and epidemiological data indicate that a variety of nutritional factors including vitamin C and E are effective to lower the risk of some types of cancer. However large prospective studies have failed to find such significant association. A comparative and combined in vitro antimutagenic potential of two antioxidant vitamins ascorbic acid (vitamin C) and α-tocopherol (vitamin E) were evaluated using Ame's Salmonella typhimurium test assay. Directly acting mutagens such as sodium azide (NaN(3)) and 4-Nitro-o-phenylenediamine (NPDA), and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were used to induce mutation in salmonella strains TA 98 and TA 100. Vitamin C significantly (P < 0.01) and dose dependently inhibited the mutagenicity induced by all the three mutagens. The percent inhibitions of vitamin C at 15 mg/plate were 33.8% (NaN(3)), 52.5 % (MNNG) and 55.4 % (NPDA). Vitamin E (15 mg/plate) was effective to inhibit mutagenicity induced by NaN3 and MNNG but did not inhibit mutation induced by NPDA. Combination of vitamins (vitamin C plus vitamin E) produced only an additive antimutagenic activity when compared to their activity at 5 mg/plate. The results of the study concluded that vitamin C is a better antimutagenic agent than vitamin E and combination of vitamins did not produce any synergistic activity.
RESUMEN
A large number of xenobiotics are reported to be potentially hepatotoxic. Free radicals generated from the xenobiotic metabolism can induce lesions of the liver and react with the basic cellular constituents - proteins, lipids, RNA and DNA. Hepatoprotective activity of aqueous ethanol extract of Zingiber officinale was evaluated against single dose of acetaminophen-induced (3g/kg, p.o.) acute hepatotoxicity in rat. Aqueous extract of Z. officinale significantly protected the hepatotoxicity as evident from the activities of serum transaminase and alkaline phosphatase (ALP). Serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and ALP activities were significantly (p<0.01) elevated in the acetaminophen alone treated animals. Antioxidant status in liver such as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase and glutathione-S-transferase (GST), a phase II enzyme, and levels of reduced glutathione (GSH) were declined significantly (p<0.01) in the acetaminophen alone treated animals (control group). Hepatic lipid peroxidation was enhanced significantly (p<0.01) in the control group. Administration of single dose of aqueous extract of Z. officinale (200 and 400mg/kg, p.o.) prior to acetaminophen significantly declines the activities of serum transaminases and ALP. Further the hepatic antioxidant status was enhanced in the Z. officinale plus acetaminophen treated group than the control group. The results of the present study concluded that the hepatoprotective effect of aqueous ethanol extract of Z. officinale against acetaminophen-induced acute toxicity is mediated either by preventing the decline of hepatic antioxidant status or due to its direct radical scavenging capacity.
Asunto(s)
Acetaminofén/toxicidad , Antioxidantes/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Hígado/metabolismo , Extractos Vegetales/farmacología , Zingiber officinale/química , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Relación Dosis-Respuesta a Droga , Femenino , Hígado/efectos de los fármacos , Hígado/patología , Extractos Vegetales/química , Ratas , Ratas Sprague-Dawley , Rizoma/químicaRESUMEN
Oxidative stress due to abnormal production of reactive oxygen molecules (ROM) is believed to be involved in the etiology of toxicities of many xenobiotics. Evidences suggested that ROM is involved in the nephrotoxicity of a widely used synthetic anticancer drug cisplatin. The nephroprotective effects of ethanol extract of Zingiber officinale alone and in combination with vitamin E (alpha-tocopherol) were evaluated using cisplatin (single dose of 10 mg/kg body wt, i.p) induced acute renal damage in mice. The results of the study indicated that Z. officinale significantly and dose dependently protected the nephrotoxicity induced by cisplatin. The serum urea and creatinine levels in the cisplatin alone treated group were significantly elevated (P<0.01) with respect to normal group of animals. The levels were reduced in the Z. officinale (250 and 500 mg/kg, p.o) plus cisplatin, vitamin E (250 mg/kg) plus cisplatin, and Z. officinale (250 mg/kg) with vitamin E plus vitamin E treated groups. The renal antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and level of reduced glutathione (GSH) were declined; level of malondialdehyde (MDA) was elevated in the cisplatin alone treated group. The activities of SOD, CAT GPx and level of GSH were elevated and level of MDA declined significantly (P<0.05) in the Z. officinale (250 and 500 mg/kg) plus cisplatin and Z. officinale (250 mg/kg) with vitamin E plus cisplatin treated groups. The protective effect of Z. officinale (250 mg/kg body wt) was found to be better than that of vitamin E (250 mg/kg body wt). The results also demonstrated that combination of Z. officinale (250 mg/kg) with vitamin E (250 mg/kg) showed a better protection compared to their 250 mg/kg alone treated groups. This study concluded that ethanol extract of Z. officinale alone and in combination with vitamin E partially ameliorated cisplatin-induced nephrotoxicity. This protection is mediated either by preventing the cisplatin-induced decline of renal antioxidant defense system or by their direct free radical scavenging activity.
Asunto(s)
Antineoplásicos/toxicidad , Cisplatino/toxicidad , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Extractos Vegetales/farmacología , Zingiber officinale/química , alfa-Tocoferol/farmacología , Animales , Catalasa/metabolismo , Creatinina/sangre , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Riñón/efectos de los fármacos , Riñón/enzimología , Enfermedades Renales/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , Extractos Vegetales/toxicidad , Rizoma/metabolismo , Superóxido Dismutasa/metabolismo , Urea/sangreRESUMEN
BACKGROUND: Oxidative stress, resulting from an imbalance between prooxidant and antioxidant systems in favor of the former, largely contributes to immune system deregulation and complications observed in end-stage renal disease (ESRD) and patients treated with hemodialysis. Reactive oxygen species and free radicals are involved in the nephrotoxicity induced by a synthetic anticancer drug cisplatin. METHODS: A comparative study on the nephroprotective effects of antioxidant vitamins (250 and 500 mg/kg, p.o.), vitamin C (ascorbic acid) and vitamin E (alpha-tocopherol), was evaluated using cisplatin (10 mg/kg body wt, i.p.) induced oxidative renal damage in mice. Urea and creatinine in serum were estimated for the renal function. Antioxidant status was estimated in kidney homogenate. RESULTS: We found that both vitamins at 500 mg/kg significantly (P<0.01) protected the nephrotoxicity induced by cisplatin. The cisplatin induced increase of urea and creatinine concentrations were reduced in the vitamins plus cisplatin (250 and 500 mg/kg, p.o.)-treated groups. However the cisplatin induced decline of renal antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities were increased only in the 500 mg/kg vitamins treated groups. Both vitamins at 250 and 500 mg/kg could increase the concentration of reduced glutathione (GSH) and protected the increase of cisplatin induced lipid peroxidation. CONCLUSIONS: Higher doses of vitamins are effective to protect oxidative renal damage and vitamin C is the better nephroprotective agent than vitamin E. The protection is mediated partially by preventing the decline of renal antioxidant status.
Asunto(s)
Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Enfermedades Renales/prevención & control , Vitaminas/farmacología , alfa-Tocoferol/farmacología , Animales , Antineoplásicos , Catalasa/metabolismo , Cisplatino , Creatinina/sangre , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Enfermedades Renales/inducido químicamente , Enfermedades Renales/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , Superóxido Dismutasa/metabolismo , Urea/sangreRESUMEN
The antimutagenic activity of the methanolic extract of the fruiting bodies of Ganoderma lucidum (Fr.) P. Krast. occurring in South India was investigated. The activity was assayed by Ames Salmonella mutagenicity test using histidine mutants of Salmonella typhimurium tester strains, TA98, TA100 and TA102. The methanolic extract of the mushroom significantly inhibited (P<0.001) the in vitro sodium azide (NaN(3)), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitro-o-phenylenediamine (NPD), and benzo[a]pyrene (B[a]P) induced his(+) revertants in a dose dependent manner. In vivo antimutagenic activity of extract was also assayed by determining the mutagenicity of the urine of rats administrated with B[a]P as a mutagen. The prior administration of extract markedly inhibited mutagenicity induced by B[a]P. The results indicated that the methanolic extract of Ganoderma lucidum occurring in South India possessed significant antimutagenic activity. The effect of B[a]P on hepatic enzymes, such as serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphtase (ALP), were also evaluated. The extract prevented the increase of SGOT, SGPT, and ALP activities consequent to B[a]P challenge, and enhanced the levels of reduced glutathione (GSH) and activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT). The extract also profoundly inhibited lipid peroxidation induced by B[a]P. The results revealed that Ganoderma lucidum extract restored antioxidant defense and prevented hepatic damage consequent to the challenge by B[a]P.
Asunto(s)
Antimutagênicos/uso terapéutico , Benzo(a)pireno/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Mutágenos/toxicidad , Reishi/química , Animales , Antimutagênicos/aislamiento & purificación , Antioxidantes/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/orina , Recuento de Colonia Microbiana , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Masculino , Metanol , Ratas , Ratas Wistar , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/crecimiento & desarrolloRESUMEN
Elevated levels of oxidative DNA lesions have been noted in many tumors and such damage is strongly implicated in the etiology of cancer. The cumulative risk of cancer increases with the fourth power of age and is associated with an accumulation of oxidative DNA damage. Many agents, synthetic or natural, that can inhibit mutation have been depicted as cancer chemopreventive agents. Antimutagenicity of the 3-hydroxy-3-methylgutaryl-CoA (HMG-CoA) reductase inhibitors atorvastatin and lovastatin was studied using the Ames Salmonella typhimurium assay. Directly acting mutagens, sodium azide (NaN(3)) and 4-nitro-o-phenylenediamine (NPDA), were used to induce mutation in Salmonella strains TA98 and TA100. The antimutagenicity of lovastatin and atorvastatin was found to be significant (p < 0.01) and dose-dependent. The percentage inhibition of a 3 mg lovastatin-treated plate was found to be 79.9% and 61.8% against NPDA- and NaN(3)-induced mutation to TA98 and TA100, respectively. Atorvastatin (0.5 mg/plate) inhibited NPDA-and NaN(3)-induced mutation to TA98 and TA100 by 78.6% and 45.5%, respectively. Atorvastatin showed antimutagenic activity at lower concentrations than lovatstatin. The results of the present study regarding the antimutagenic activity of atorvastatin and lovastatin suggested their therapeutic application as cancer chemopreventive agents.