Berberine exerts nephroprotective effect against cisplatin-induced kidney damage through inhibition of oxidative/nitrosative stress, inflammation, autophagy and apoptosis.

Abstract

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.

• Authors: Robert Domitrović, Olga Cvijanović, Ester Pernjak-Pugel, Marko Skoda, Lorena Mikelić, Zeljka Crnčević-Orlić
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 62 Pg. 397-406 (Dec 2013) ISSN: 1873-6351 [Electronic] England
• PMID: 24025684 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Aldehydes
• Protective Agents
• Berberine
• 3-nitrotyrosine
• Tyrosine
• Creatinine
• Cytochrome P-450 CYP2E1
• 4-hydroxy-2-nonenal
• Cisplatin

Topics

• Aldehydes (metabolism)
• Animals
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Berberine (pharmacology)
• Blood Urea Nitrogen
• Cisplatin (adverse effects)
• Creatinine (blood)
• Cytochrome P-450 CYP2E1 (metabolism)
• Kidney (drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Nephritis (drug therapy, metabolism)
• Oxidative Stress (drug effects)
• Protective Agents (pharmacology)
• Tyrosine (analogs & derivatives, metabolism)