Cisplatin-induced nephrotoxicity is related to increased reactive oxygen species and inflammatory cytokines in the kidney. Sinapic acid (SA) has both antioxidant and anti-inflammatory activities.

We determined the effects of SA on cisplatin-induced nephrotoxicity in rats, and the potential mechanisms by which it augments antioxidant responses and attenuates nephrotoxicity related to oxidative/nitrosative stress, apoptosis, and inflammation.

Kidney function markers (i.e., serum urea, uric acid, creatinine, and lactate dehydrogenase), oxidative stress markers (i.e., lipid peroxidation and nitric oxide), antioxidant systems (i.e., superoxide dismutase, catalase, and reduced glutathione), inflammation markers (i.e., tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and myeloperoxidase [MPO]), apoptotic markers (caspase 3, Bax, and Bcl-2), and the levels of nuclear factor-κB (NF-κB [p65]), Nrf2, and heme oxygenase-1 (HO-1) were assessed. Histopathological examinations of the kidney were also used to evaluate cisplatin-induced nephrotoxicity.

SA (10 and 20mg/kg) pretreatment ameliorated kidney function, upregulated antioxidant levels, and downregulated lipid peroxidation and nitric oxide levels in cisplatin-injected rats, resulting in significant reductions in oxidative stress and replenishment of endogenous antioxidant enzymes. Cisplatin upregulated cytokines (i.e., TNF-α and IL-6) and MPO, increased apoptosis, and downregulated Nrf2 and HO-1. SA pretreatment downregulated the pro-apoptotic caspase-3 and Bax proteins, and upregulated the anti-apoptotic Bcl-2 protein. SA pretreatment also alleviated the extent of histological impairment and reduced neutrophil infiltration in renal tubules.

The results suggest that the Nrf2/HO-1 signaling pathway may be the primary target for protection from cisplatin-induced nephrotoxicity by SA, and that SA reduces oxidative stress, inflammation, and apoptosis by inhibiting NF-κB.