Abstract
Cisplatin is one of the most used drugs in the therapy of different types of cancer. However, its use is limited by nephrotoxicity. This study investigated the effects of a commercially available grape pomace extract (GE) from Vitis vinifera on cisplatin-induced kidney toxicity in rats. Sixty-four male Wistar albino rats were randomly divided into eight groups. Groups 1–3 were controls, receiving 0.9% saline and doses 1 and 2 of GE respectively. Cisplatin was given to groups 4–8. Two groups received pretreatment with GE, while another two groups received pre- and post-treatment with GE. Blood samples were collected and all animals sacrificed. Kidneys were harvested for histopathological analysis. GE significantly increased blood creatinine and urea levels, the severity of kidney histopathological damage, and mortality in all cisplatin groups, except for group 7 which received pre- and post-treatment with a low dose of GE. Renal toxicity was determined by mortality and severe histopathological renal lesions. Additionally, the serum total antioxidant capacity (TAC) was not significantly modified in the treated groups compared to the control. These results indicate that the GE did not have a protective effect on cisplatin-induced nephrotoxicity; on the contrary, GE accentuated the toxic effect of cisplatin.
Highlights
One of the classical anti-cancer drugs used in solid cancer is cisplatin (cis-diamminedichloroplatinum (II)) (CIS), and this is still commonly used today in numerous oncological treatment regimens
CIS renal toxicity is generally considered to be influenced by several factors, the most notable being the destruction of renal epithelial cells with subsequent loss of kidney function, damaging effects on mtDNA, and the activation of apoptosis and necrosis pathways inside the cell
In vivo experimental studies have provided evidence of the nephroprotective effect of resveratrol on the toxicity induced by drugs or toxins
Summary
One of the classical anti-cancer drugs used in solid cancer is cisplatin (cis-diamminedichloroplatinum (II)) (CIS), and this is still commonly used today in numerous oncological treatment regimens. In day to day clinical practice, salt-based volume expansion is used with added diuretics such as mannitol or furosemide [6,7,8]. Another noteworthy strategy is the administration of Amifostine to treat ovarian cancers, with its protective mechanism still being a debated topic in literature [9,10,11]. In vivo experimental studies have provided evidence of the nephroprotective effect of resveratrol (a major component in grape juice) on the toxicity induced by drugs or toxins (gentamicin, cyclosporine, cisplatin, arsenic trioxide). This study investigated the dose–response effect of grape pomace extract (GE) on CIS-induced renal changes in rats
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