Ameliorative Effect of Daidzein on Cisplatin-Induced Nephrotoxicity in Mice via Modulation of Inflammation, Oxidative Stress, and Cell Death

الملخص EN

Oxidative stress and inflammation are part and parcel of cisplatin-induced nephrotoxicity.

The purpose of this work is to study the role of soy isoflavone constituent, daidzein, in cisplatin-induced renal damage.

Cisplatin-induced nephrotoxicity was evident by the histological damage in proximal tubular cells and by the increase in serum neutrophil gelatinase-associated lipocalin (NGAL), blood urea nitrogen (BUN), creatinine, and urinary kidney injury molecule-1 (KIM-1).

Cisplatin-induced cell death was shown by TUNEL staining and caspase-3/7 activity.

Daidzin treatment reduced all kidney injury markers (NGAL, BUN, creatinine, and KIM-1) and attenuated cell death (apoptotic markers).

In cisplatin-induced kidney injury, renal oxidative/nitrative stress was manifested by the increase in lipid peroxidation and protein nitration.

Cisplatin induced the reactive oxygen species-generating enzyme NOX-2 and impaired antioxidant defense enzyme activities such as glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities.

Cisplatin-induced oxidative/nitrative stress was attenuated by daidzein treatment.

Cisplatin induced CD11b-positive macrophages in kidneys and daidzein attenuated CD11b-positive cells.

Daidzein attenuated cisplatin-induced inflammatory cytokines tumor necrosis factor α (TNFα), interleukin 10 (IL-10), interleukin 18 (IL-18), and monocyte chemoattractant protein-1 (MCP-1).

Daidzein attenuated cell death in vitro.

Our data suggested that daidzein attenuated cisplatin-induced kidney injury through the downregulation of oxidative/nitrative stress, immune cells, inflammatory cytokines, and apoptotic cell death, thus improving kidney regeneration.