Falcarindiol attenuates cisplatin-induced nephrotoxicity through the modulation of NF-kB and Nrf2 signaling pathways in mice

Abstract

Cisplatin is a therapeutic drug widely used to treat various solid tumors. Nephrotoxicity is a well-known side effect in patients treated with cisplatin. Falcarindiol (FAD), natural polyacetylene compound greatly found in Apiaceae family, has anti-cancer, -bacterial, -inflammatory and -oxidant activity which is utilized in the present study. Thirty male C57BL/6 mice were randomly divided into five groups of six each; sham, cisplatin (15 mg/kg), cisplatin + FAD (50 and 100 mg/kg/day), and FAD (100 mg/kg/day). Cisplatin administration elevated the concentrations of BUN and creatinine, as well as kidney histopathologic damage. On the other hand, FAD treatment attenuated cisplatin-induced injury, and also down-regulated mRNA levels of TNF-α and IL-1β together with protein expression of p-NF-kB p65. Moreover, FAD induced the protein expression of p-AMPK and nuclear Nrf2 accompanied by its respective target genes such as NQO-1 and HO-1 in a dose-dependent manner. In conclusion, the findings collectively characterize FAD as a drug candidate to treat cisplatin-induced nephrotoxicity thorough down-regulation of NF-kB signaling pathway in mice

Mechanisms of Action of Polyacetylenes’ Anti-Inflammatory Function and Their Potential in Cancer Chemoprevention and Treatment

“…Cisplatin, which has nephrotoxicity as a side effect, is a therapeutic drug for various solid tumours. FaDOH has been found to attenuate cisplatin-induced injury and down-regulate mRNA levels of TNF-α, IL-1β and protein expression of p-NF-kB p65 in mice [96].…”

Pathways Affected by Falcarinol-Type Polyacetylenes and Implications for Their Anti-Inflammatory Function and Potential in Cancer Chemoprevention

“…Cisplatin, which has nephrotoxicity as a side effect, is a therapeutic drug for various solid tumours. FaDOH attenuates cisplatin-induced injury and down-regulates mRNA levels of TNF-α, IL-1β and the protein expression of p-NF-κB p65 in mice [ 111 ].…”