Sinomenine mitigates cisplatin-induced kidney injury by targeting multiple signaling pathways

Abstract

Sinomenine is a pharmacologically active alkaloid with antioxidant and anti-inflammatory properties. We aimed to investigate the mechanism of renoprotective activity of sinomenine in kidney injury induced by cisplatin (CP). Sinomenine (5 mg/kg) was administered to mice orally in two doses, the second day after intraperitoneal application of CP (13 mg/kg). Sinomenine ameliorated kidney injury and decreased serum levels of urea and creatinine and renal expression of NGAL and KIM-1. The increase in HO-1, 4-HNE, 3-NT and TNF-α renal expression was mitigated by sinomenine. Additionally, sinomenine reduced the expression of p21, Bax, Noxa, caspase-3 and -8 and PARP1 cleavage in mice kidneys as well as the number of TUNEL-positive cells. Sinomenine attenuated CP-induced activation of ERK1/2, Akt, FOXO3a, STAT3 and NF-κB and restored Sirtuin 6 expression. In the human proximal tubular cell line HK2, sinomenine 100 μM reduced the toxic effect of CP 30 μM. Our current findings suggest that sinomenine suppresses CP-induced oxidative stress, inflammation and apoptosis in mice kidneys by targeting multiple signaling pathways.

Keywords: Apoptosis; Cisplatin; Inflammation; Kidney; Oxidative stress; Sinomenine.