Preclinical evaluation of phloretin on cisplatin induced nephrotoxicity in peri-menopausal mouse model

Pharmacy

Cisplatin is an effective on cancer like prostate cancer, bladder cancer, overian cancer, lung cancer that causes remarkable toxicity to the kidney, particularly to glomerular filter, by generating reactive oxygen species. From literature it is evident that women are more prone to Cisplatin induced nephrotoxicity, and the women >45 yrs of age are more prone to cisplatin induced nephrotoxicity. More specifically women of 45-55 age group (peri-menopausal age) are more prone for cisplatin induced nephrotoxicity. It has also become evident that inflammation provoked by injury to renal epithelial cells serves to amplify kidney injury and dysfunction.In the Cisplatin induced nephrotoxicity study in perimenopausal mouse model, Cisplatin treated group significantly increased level of serum creatinine, BUN, ALP and decreased the level of albumin. Cisplatin treated mice the decrease the level of GSH, SOD and increased the level of LPO. Cisplatin treated animals shows the damaged to the kidney. Phloretin shows the significant protective effect in kidney function parameters (CRE, BUN and albumin in serum), oxidative stress parameters and microscopic tissue injury in histopathology studies. While the phloretin treatment with low and high-dose (20–60 mg/kg) was possessed the significant protective effects against the cisplatin-induced renal damage, more importantly it also increased survival and delayed mortality in cisplatin treated perimenopausal mice model. The observed results of the current research work clearly exhibited the clinical potential of phloretin as cotreatment with cisplatin for cancer treatment in perimenopausal women to reduce cisplatin induced nephrotoxicity.

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