title: 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.affiliation: Department of Pediatrics, Jingling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.forename: Zheng-Kun
authors.initials: ZK
authors.lastname: Xia
authors.forename: Xian-Guo
authors.initials: XG
authors.lastname: Ren
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Zhang
authors.forename: Ya-Hao
authors.initials: YH
authors.lastname: Liang
authors.forename: Guang-Ling
authors.initials: GL
authors.lastname: Liu
mesh_terms: D000818:Animals; D004317:Doxorubicin / Q000009:adverse effects* / Q000032:analysis / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000032:analysis / Q000097:blood / Q000652:urine; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000097:blood / Q000652:urine; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000097:blood / Q000652:urine; D008954:Models, Biological; D015394:Molecular Structure; D009019:Morphinans / Q000494:pharmacology* / Q000627:therapeutic use; D009401:Nephrosis / Q000139:chemically induced*; D047493:PPAR alpha / Q000032:analysis / Q000097:blood / Q000652:urine; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000097:blood / Q000652:urine
chemical_list: D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009019:Morphinans; C407223:NPHS2 protein; D047493:PPAR alpha; D014409:Tumor Necrosis Factor-alpha; C113267:nephrin; C009271:sinomenine; D004317:Doxorubicin