Protective effects of sinomenine against doxorubicin-induced nephrosis in rats

Abstract

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-α and IL-1β levels, nephrin, podocin, α-actinin-4, and peroxisome proliferator-activated receptor-α (PPAR-α) 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-α 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 α-actinin-4. DOX significantly increased serum TNF-α and IL-1β compared with those in control rats, and 1 significantly reduced the serum levels of TNF-α and IL-1β. SN ameliorates DOX-induced nephrotic syndrome in rats, resulting in a modulation of renal nephrin, podocin expression, and thereby protecting podocytes from injury.

Keywords:

• sinomenine
• doxorubicin nephrosis
• nephrin
• PPAR-α
• podocyte injury

Acknowledgments

This work was financially supported by a grant from the College Graduate Research and Innovation Projects of Jiangsu Province of China, and Key Medical Personnel Fund of Jiangsu Province of China (RC2007115).

Notes

1. J. Zhang and H. Rong contributed equally to the work.

Additional information

Notes on contributors

Jie Zhang

1

Rong Hu

1