Protective effects of sinomenine against doxorubicin-induced nephrosis in rats.

Sinomenine (SN, 1) is a pure compound extracted from the Sinomenium acutum plant. We investigated the protective effects and mechanism of action of SN in a rat model of doxorubicin (DOX)-induced nephrosis. Nephrosis was induced by a single dose of 5 mg/kg DOX, and DOX-treated rats received a daily i.p. injection of 10 or 30 mg/kg SN, or saline (n = 6). Urine and serum biochemical parameters, serum TNF-alpha and IL-1 beta levels, nephrin, podocin, alpha-actinin-4, and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) protein expression, and renal ultrastructure were examined at day 28. Compound 1 significantly attenuated the effect of DOX on urine and serum biochemical parameters. Electron microscopy demonstrated that 1 suppressed DOX-induced increases in foot process width. Compared with those in control rats, nephrin, podocin, and PPAR-alpha protein expressions decreased in the glomeruli of DOX-treated rats, and this effect was significantly attenuated by 1. However, no appreciable alterations were observed in the expression level of alpha-actinin-4. DOX significantly increased serum TNF-alpha and IL-1 beta compared with those in control rats, and 1 significantly reduced the serum levels of TNF-alpha and IL-1 beta. SN ameliorates DOX-induced nephrotic syndrome in rats, resulting in a modulation of renal nephrin, podocin expression, and thereby protecting podocytes from injury.