Indole-3-carbinol protects against cisplatin-induced acute nephrotoxicity: role of calcitonin gene-related peptide and insulin-like growth factor-1

Abstract

Nephrotoxicity associated with the clinical use of the anticancer drug cisplatin is a limiting problem. Thus, searching for new protective measures is required. Indole-3-carbinol is a powerful anti-oxidant, anti-inflammatory and anti-tumor agent. The present study aimed to investigate the potential protective effect of indole-3-carbinol against cisplatin-induced acute nephrotoxicity in rats. Rats were pre-treated with 20 mg/kg indole-3-carbinol orally before giving cisplatin (7 mg/kg). Cisplatin-induced acute nephrotoxicity was demonstrated where relative kidney weight, BUN and serum creatinine were significantly increased. Increased oxidative stress was evident in cisplatin group where GSH and SOD tissue levels were significantly depleted. Also, lipid peroxidation and NOX-1 were increased as compared to the control. Additionally, renal expression of pro-inflammatory mediators was induced by cisplatin. Cisplatin-induced cell death was shown by increased caspase-3 and decreased expression of EGF, IGF-1 and IGF-1 receptor. Nephrotoxicity, oxidative stress, inflammation and apoptotic effects induced by cisplatin were significantly ameliorated by indole-3-carbinol pre-treatment. Besides, the role of CGRP in cisplatin-induced nephrotoxicity was explored. Furthermore, cisplatin cytotoxic activity was significantly enhanced by indole-3-carbinol pre-treatment in vitro. In conclusion, indole-3-carbinol provides protection against cisplatin-induced nephrotoxicity. Also, reduced expression of CGRP may play a role in the pathogenesis of cisplatin-induced renal injury.

Therapeutic Potential and Molecular Mechanisms of Emblica officinalis Gaertn in Countering Nephrotoxicity in Rats Induced by the Chemotherapeutic Agent Cisplatin

“…Normally, it is excreted by the kidneys, primarily by glomerular filtration but also by proximal tubular secretion with little or no reabsorption. If there is deterioration in kidney function, serum level of creatinine rises ( El-Naga, 2014 ; Changizi-Ashtiyani et al, 2016 ; El-Naga and Mahran, 2016 ). Also, concomitant decline in urinary creatinine clearance is observed vis a vis raised serum creatinine levels.…”

Ganoderma lucidum Prevents Cisplatin-Induced Nephrotoxicity through Inhibition of Epidermal Growth Factor Receptor Signaling and Autophagy-Mediated Apoptosis

“…Kang et al [71] have documented that the combined action of oxidative stress imbalance and autophagy defects causes abnormal cell apoptosis which leads to the occurrence of AKI [71]. Indeed, it is undeniable that the disruption of growth factors and their receptors play a role in CDDP-induced renal injuries [56]. In renal proximal tubular cells, CDDP also activated the EGFR, which is involved in cell death rather than survival under these conditions [73].…”

Protein extracted from Porphyra yezoensis prevents cisplatin-induced nephrotoxicity by downregulating the MAPK and NF-κB pathways

“…involve accumulation of potentially toxic compounds in the tubular fluid, which then diffuse into the highly permeable tubular cells (13). Numerous studies have demonstrated that several mechanisms, including oxidative stress, DNA damage and inflammatory responses, mediate cisplatin-induced nephrotoxicity (13,16). The key pathological occurrences in cisplatin-induced nephrotoxicity are renal tubular cell injury and death (14,17).…”