Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5850377 | Food and Chemical Toxicology | 2013 | 10 Pages |
â¢Histopathological changes and the increase in serum creatinine and BUN induced by cisplatin were ameliorated by berberine.â¢Berberine significantly reduced the increase in renal CYP2E1, 4-HNE, 3-NT and HO-1 expression.â¢The expression of NF-κB, TNF-α and COX-2 in the kidneys was markedly suppressed by berberine.â¢Treatment with berberine reduced the expression of p53, cleaved caspase-3 and LC3B in the kidneys.â¢Berberine inhibited renal oxidative stress, inflammation, apoptosis and autophagy induced by cisplatin.
The aim of this study was to investigate the therapeutic activity of isoquinoline alkaloid berberine against cisplatin (CP)-induced nephrotoxicity in mice. Berberine was administered at daily doses of 1, 2 and 3 mg/kg by gavage for two successive days, 48 h after intraperitoneal CP injection (13 mg/kg). Mice were sacrificed 24 h after the last dose of berberine. Histopathological changes and the increase in serum creatinine and blood urea nitrogen (BUN) induced by CP were significantly ameliorated by berberine in a dose-dependent manner. Additionally, oxidative/nitrosative stress, evidenced by the increase in renal 4-hydroxynonenal (4-HNE), 3-nitrotyrosine (3-NT), cytochrome P450 E1 (CYP2E1) and heme oxygenase (HO-1) expression, was significantly reduced. The expression of nuclear factor-kappaB (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was markedly suppressed by berberine, indicating the inhibition of inflammatory response. Treatment of CP-intoxicated animals with berberine also significantly reduced the expression of p53, active caspase-3 as well as autophagy marker light chain 3B (LC3B) in the kidneys. The results of the current study showed the nephroprotective activity of berberine against CP-induced renal injury, which could be attributed to the inhibition of oxidative/nitrosative stress, inflammation, autophagy and apoptosis.