Open AccessPitavastatin attenuates cisplatin‐induced renal injury by targeting MAPK and apoptotic pathways
Author(s) -
Kaushik Swati,
Tomar Ameesha,
Puthanmadhom Narayanan Susrutha,
Nag Tapas Chandra,
Arya Dharamvir Singh,
Bhatia Jagriti
Publication year - 2019
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.13090
Subject(s) - pitavastatin , cisplatin , pharmacology , apoptosis , dna fragmentation , medicine , mapk/erk pathway , kidney , toxicity , acute kidney injury , endocrinology , chemistry , chemotherapy , programmed cell death , biochemistry , signal transduction , atorvastatin
Abstract Objective Anti‐neoplastic drug cisplatin is prescribed widely for treatment of a variety of malignancies. Its use has been restricted lately due to severe renal toxicity. The purpose of current study was to investigate the effect of pitavastatin (a hypolipidaemic drug) in cisplatin‐induced acute kidney injury in rats. Method Male Wistar rats (150–200 g) were treated with different doses of pitavastatin (0.16, 0.32 and 0.64 mg/kg per day p.o.; 10 days). On 7th day of the study, rats were administered cisplatin (8 mg/kg i.p.). Rats were euthanized (11th day), and blood and tissues were processed to evaluate biochemical, histopathological and ultrastructural parameters along with the analysis of immunohistochemistry and DNA‐fragmentation studies. Protein expressions were analysed to demonstrate the underlying molecular mechanisms. Key findings In the study group with cisplatin insult, KFT parameters were found to be elevated, concentration of apoptotic markers was found to be increased, histopathological and ultramicroscopical architecture was found to be distorted and the expression of MAPK proteins was also found to be elevated as compared to the normal group rats. Pitavastatin treatment alleviated all these anomalies. Conclusion Cisplatin‐induced acute renal injury was improved on administration of pitavastatin via inhibition of MAPK and apoptotic pathway.