title: Molecular mechanisms underlying attenuation of cisplatin-induced acute kidney injury by epicatechin gallate.
abstract: Cisplatin, a platinum compound, is used as a first-line agent against various forms of solid cancers. Nephrotoxicity is an important adverse effect of cisplatin therapy, which involves increased oxidative stress, inflammation, apoptosis, and activation of the mitogen-activated protein kinase (MAPK) pathway. It is well known that the bioactive compounds present in green tea are used to treat various disorders due to their biological activities. With this background, the present study was aimed to investigate the effect of epicatechin gallate (ECG), a green tea polyphenol, in cisplatin-induced nephrotoxicity in rats. To achieve this, ECG (1.25, 2.5, and 5 mg/kg; intraperitoneal (i.p.)) was administered to male albino Wistar rats for the period of 10 days. On the 7th day, a single i.p. injection of cisplatin (8 mg/kg) was injected into rats to produce kidney injury and the animals were then killed on the 10th day. Cisplatin toxicity was associated with enhanced oxidative stress, impaired renal function along with marked tubular necrosis in Histopathology. Furthermore, cisplatin activated the MAPK pathway, which contributed to inflammation and apoptosis in the kidney of treated rats. In contrast, ECG (5 mg/kg) pretreatment normalized cisplatin-induced oxidative stress, renal function, and histopathological changes. ECG also prevented the activation of the MAPK pathway, and attenuated inflammation and apoptosis in rats. These findings suggest that ECG prevented cisplatin-induced oxidative stress, inflammation, and apoptosis by downregulating the MAPK pathway and resulted in improved renal function.
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Salma
authors.initials: S
authors.lastname: Malik
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Kapil
authors.initials: K
authors.lastname: Suchal
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Jagriti
authors.initials: J
authors.lastname: Bhatia
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Nanda
authors.initials: N
authors.lastname: Gamad
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Dinda
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Yogendra Kumar
authors.initials: YK
authors.lastname: Gupta
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Dharamvir Singh
authors.initials: DS
authors.lastname: Arya
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000097:blood; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D020011:Protective Agents; D002392:Catechin; C062669:epicatechin gallate; D003404:Creatinine; D002945:Cisplatin