ubiquinone and epigallocatechin-gallate

Despite the extensive use of cisplatin (CP) as a chemotherapeutic agent, its clinical use is often restricted by undesirable side effects, such as toxicity to normal tissues. The aim of this study was to probe the effect of a combinatorial treatment of low multiple doses of antioxidants on CP-induced toxicity and the mitochondrial apoptotic pathway in hepatocytes. Animals received a single toxic dose of CP (7.5 mg/kg body weight) with or without combined multiple doses of epigallocatechin gallate (EGCG) and coenzyme Q10 (CoQ10) (15 and 5 mg/kg body weight, respectively). CP-treated animals showed altered biochemical parameters, denoting hepatotoxicity, which was markedly improved by the multidose treatment with EGCG + CoQ10. The increased levels of oxidants found in the cytosolic and mitochondrial fractions isolated from the liver of CP-administered rats were significantly attenuated by the combinatorial doses of antioxidants. EGCG + CoQ10 ameliorated the CP-induced compromised antioxidant defenses, oxidative modification of macromolecules, decreased activities of respiratory chain enzymes, altered membrane depolarization, and swelling of liver mitochondria. Furthermore, EGCG + CoQ10 treatment inhibited CP-induced apoptosis by suppressing the activation and mitochondrial accumulation of proapoptotic proteins and preventing the inhibition of antiapoptotic protein expression, cytochrome c efflux, caspase-3 activation, and DNA fragmentation. Histological findings further confirmed the protective effects of EGCG + CoQ10 against CP-induced cellular injury. Our findings revealed that the combination of EGCG and CoQ10, owing to their individual antioxidant properties, can be an effective remedy, which by maintaining redox hemostasis attenuate the mitochondrial stress-mediated molecular and cellular processes involved in CP-induced liver toxicity and cell death.

Topics: Animals; Apoptosis; Catechin; Chemical and Drug Induced Liver Injury; Cisplatin; Hepatocytes; Liver; Male; Mitochondria, Liver; Oxidative Stress; Rats; Rats, Wistar; Ubiquinone

Cisplatin (CP), a platinum based anticancer drug is used as one of the first-line therapy for the treatment of different types of solid tumors. However, CP-induced side effects particularly, nephrotoxicity is a major concern. A single nephrotoxic dose (7 mg/kg body weight) of CP was administered in rats with or without, pre and post combined multidoses of epigallocatechin gallate (EGCG) and coenzyme Q10 (CoQ10) (15 and 5 mg/kg body weight respectively). CP administration resulted in marked increase in the nephrotoxic parameters with alterations in the oxidative and nitrosative stress markers. The concentration of inflammatory, as well as apoptotic markers were markedly up-regulated in the kidney of the CP-treated group. Furthermore, CP resulted in histological injury in the renal tissues. Combined antioxidant treatment significantly (p < 0.01) attenuated CP-induced oxidative stress, nitrosative stress, inflammatory and apoptotic parameters. Moreover, an improvement in the histopathological changes confirmed the nephroprotective effect of antioxidant treatment. In conclusion, our study indicates that the combinatorial multidoses of EGCG and CoQ10 ameliorate the cisplatin-mediated pathogenesis by improving renal oxidative/nitrosative status, inflammation and apoptosis and thus can be used as a promising protective agent to increase the efficacy of the drug by minimizing its major side effect i.e. nephrotoxicity.

Topics: Animals; Antineoplastic Agents; Apoptosis; Catechin; Cisplatin; Inflammation; Kidney; Male; Nitrosation; Oxidative Stress; Rats; Rats, Wistar; Ubiquinone

The nephroprotective effect of coenzyme Q10 and epigallocatechin gallate was investigated in rats with acute renal injury induced by a single nephrotoxic dose of cisplatin. Two days prior to cisplatin administration, epigallocatechin gallate and coenzyme Q10 alone and in four different combinations were given for 6 days. The treatment with antioxidants significantly protected the cisplatin-induced increase in the levels of blood urea nitrogen and serum creatinine. Both the antioxidants alone or in different combinations significantly compensated the increased malondialdehyde and reduced glutathione levels. Moreover, the decrease in the activities of superoxide dismutase, catalase, and glutathione peroxidase and the concentration of selenium, zinc, and copper ions were significantly attenuated in renal tissue. In conclusion, epigallocatechin gallate and coenzyme Q10 are equally effective against cisplatin-induced nephrotoxicity, whereas the intervention by combining these two antioxidants was found to be highly effective at low doses in attenuating oxidative stress in rat kidney.

Topics: Animals; Antineoplastic Agents; Antioxidants; Catechin; Cisplatin; Creatinine; Kidney; Kidney Diseases; Male; Micronutrients; Oxidative Stress; Oxidoreductases; Rats; Rats, Wistar; Ubiquinone; Urea