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.

• Authors: Jie Zhang, Rong Hu, Zheng-Kun Xia, Xian-Guo Ren, Li-Wen Zhang, Ya-Hao Liang, Guang-Ling Liu
• Journal: Journal of Asian natural products research (J Asian Nat Prod Res) Vol. 14 Issue 7 Pg. 678-87 ( 2012) ISSN: 1477-2213 [Electronic] England
• PMID: 22582804 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1beta
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• Morphinans
• NPHS2 protein
• PPAR alpha
• Tumor Necrosis Factor-alpha
• nephrin
• sinomenine
• Doxorubicin

Topics

• Animals
• Doxorubicin (adverse effects, analysis, pharmacology)
• Interleukin-1beta (analysis, blood, urine)
• Intracellular Signaling Peptides and Proteins (analysis, blood, urine)
• Kidney Glomerulus (drug effects, metabolism, ultrastructure)
• Male
• Membrane Proteins (analysis, blood, urine)
• Models, Biological
• Molecular Structure
• Morphinans (pharmacology, therapeutic use)
• Nephrosis (chemically induced)
• PPAR alpha (analysis, blood, urine)
• Rats
• Tumor Necrosis Factor-alpha (analysis, blood, urine)