Evaluation of Ameliorative Effect of Quercetin and Candesartan in Doxorubicin-Induced Cardiotoxicity

Abstract

Background Several mechanisms have been explored for the anthracycline myocardial toxicity. These are free-radical generation, myocyte apoptosis, lipid peroxidation, mitochondrial deterioration, and direct repression of muscle-specific gene expression. Adriamycin (Doxorubicin) is a potent anti-cancer agent. Adriamycin in prolonged use is fatal and generates free radicals that lead to dose-dependent cardiac toxicity. Objective The intent of the study was to explore the protective activity of candesartan and quercetin in cardiomyopathy induced by doxorubicin in rats. Methods To induce cardiac toxicity, rats were intraperitoneally treated with doxorubicin (06 equivalent injections of 2.5 mg/kg, i. p. at 48 hour interval for 02 consecutive weeks to achieve a cumulative dose of 15 mg/kg). Individual and combined oral treatment of candesartan (5 mg/kg/day) and quercetin (10 mg/kg/day) was administered for four weeks. Results Following cardiomyopathy, heart/body weight ratio (3.526 × 10 −3 ), serum creatine kinase (352.4±16.99 IU/L), lactate dehydrogenase (661.7±20.45 IU/L) levels were elevated in addition to altered lipid profile (TC – 118.4±4.25 mg/dL, TG – 263.3±9.99 mg/dL, VLDL – 52.66±1.99 mg/dL, LDL – 52.99±5.80 mg/dL and HDL – 12.78±0.36 mg/dL). The pre-cotreatment of candesartan and quercetin significantly restored the values to normal. The increased level of lipid peroxides (33.12±1.63 µmol/mg protein), serum troponin-T (1.82 ± 0.11 pg/mL) and nitric oxide (13.33±0.73 nmol/mg protein) level along with attenuating antioxidant profile, ie catalase, glutathione and superoxide dismutase (1.43±0.12 nmol/mg protein, 8.48±0.42 nmol/mg protein and 2.09±0.031 U/mg protein) were reversed to normal. Morphometry and histopathologic changes represented a beneficial effect of single and combination pre-cotreatment of drugs which significantly decreases adriamycin cardiac toxicity. Conclusion The overall result depicts more beneficial and cardioprotective effect of quercetin and candesartan combination as compared to their individual effects in doxorubicin treated animals. Therefore, this combination might be a suitable option to treat the cardiotoxic effect of doxorubicin.

A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs

“…Paclitaxel-induced neurotoxicity has been reported to be suppressed by the addition of antioxidants (such as docosahexaenoic acid, acetyl-L-carnitine hydrochloride, N -acetyl-L-cysteine, and sodium ascorbate) in cultured cells [ 31 ]. Also, in animal studies in rats, DOX-induced neurotoxicity and behavior were potentially protected by coenzyme Q10 [ 32 ], and DOX-induced cardiotoxicity is significantly suppressed with candesartan and quercetin [ 33 ]. For Compound A , we plan to search for drugs that alleviate the neurotoxicity and enhance the toxicity to OSCC.…”