Combined treatment of epigallocatechin gallate and Coenzyme Q10 attenuates cisplatin-induced nephrotoxicity via suppression of oxidative/nitrosative stress, inflammation and cellular damage.
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.
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, Saudi Arabia. Electronic address: sabmehdi@ksu.edu.sa.
Sabiha
S
Fatima
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, Saudi Arabia.
Noura
N
Al-Mohaimeed
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, Saudi Arabia.
Yazeed
Y
Al-Shaikh
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, Saudi Arabia.
Poonam
P
Tyagi
College of Medical Rehabilitation, Qassim University, Buraidah, 52451, Qassim, Saudi Arabia.
Naheed
N
Banu
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, 202002, India.
Shirin
S
Hasan
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, Saudi Arabia.
Sadia
S
Arjumand
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002945:Cisplatin / Q000633:toxicity*; D007249:Inflammation / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D015538:Nitrosation; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; D014451:Ubiquinone; D002392:Catechin; C045651:epigallocatechin gallate; C024989:coenzyme Q10; D002945:Cisplatin
Apoptosis; Cisplatin; Coenzyme Q10; EGCG; Inflammation; Nephrotoxicity; Oxidative stress/nitrosative stress