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

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-alpha 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-KB and restored Sirtuin 6 expression. In the human proximal tubular cell line HK2, sinomenine 100 mu M reduced the toxic effect of CP 30 mu M. Our current findings suggest that sinomenine suppresses CP-induced oxidative stress, inflammation and apoptosis in mice kidneys by targeting multiple signaling pathways.

Automated summary

Sinomenine has been found to alleviate kidney injury caused by cisplatin by targeting multiple signaling pathways to reduce oxidative stress, inflammation and apoptosis.