Puerarin protects rat kidney from lead-induced apoptosis by modulating the PI3K/Akt/eNOS pathway

• Published in: Toxicology and applied pharmacology 2012-02, Vol.258 (3), p.330-342
• Main Authors: Liu, Chan-Min, Ma, Jie-Qiong, Sun, Yun-Zhi
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ACETATES; Akt; Animals; ANTIOXIDANTS; Antioxidants - administration & dosage; Antioxidants - pharmacology; APOPTOSIS; Apoptosis - drug effects; Biological and medical sciences; BIOLOGICAL RECOVERY; Chemical and industrial products toxicology. Toxic occupational diseases; CREATININE; Dose-Response Relationship, Drug; DRINKING WATER; GLUTATHIONE; Glutathione - drug effects; Glutathione - metabolism; In Situ Nick-End Labeling; INHIBITION; INJURIES; Isoflavones - administration & dosage; Isoflavones - pharmacology; Kidney; Kidney - drug effects; Kidney - pathology; KIDNEYS; Lipid Peroxidation - drug effects; LIPIDS; Male; Medical sciences; Metals and various inorganic compounds; MITOCHONDRIA; NITRIC OXIDE; Nitric Oxide Synthase Type III - metabolism; Organometallic Compounds - toxicity; OXIDATION; Oxidative Stress - drug effects; OXYGEN; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Puerarin; RATS; Rats, Wistar; Reactive Oxygen Species - metabolism; ROS; Signal Transduction - drug effects; Toxicology; UREA; URIC ACID
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2011.11.015

Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. However, its protective effects against lead (Pb) induced injury in kidney have not been clarified. The aim of the present study was to investigate the effects of puerarin on renal oxidative stress and apoptosis in rats exposed to Pb. Wistar rats were exposed to lead acetate in the drinking water (500 mg Pb/l) with or without puerarin co-administration (100, 200, 300 and 400 mg PU/kg intragastrically once daily) for 75 days. Our data showed that puerarin significantly prevented Pb-induced nephrotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of kidney damage (serum urea, uric acid and creatinine) and histopathological analysis. Moreover, Pb-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of intracellular reduced glutathione (GSH) level in kidney, were suppressed by treatment with puerarin. Furthermore, TUNEL assay showed that Pb-induced apoptosis in rat kidney was significantly inhibited by puerarin. In exploring the underlying mechanisms of puerarin action, we found that activities of caspase-3 were markedly inhibited by the treatment of puerarin in the kidney of Pb-treated rats. Puerarin increased phosphorylated Akt, phosphorylated eNOS and NO levels in kidney, which in turn inactivated pro-apoptotic signaling events including inhibition of mitochondria cytochrome c release and restoration of the balance between pro- and anti-apoptotic Bcl-2 proteins in kidney of Pb-treated rats. In conclusion, these results suggested that the inhibition of Pb-induced apoptosis by puerarin is due at least in part to its antioxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway. [Display omitted] ► Puerarin prevented lead-induced nephrototoxicity. ► Puerarin reduced lead-induced increase in ROS and TBARS production in kidney of rats. ► Puerarin activated the PI3K/Akt/eNOS pathway in kidney. ► Puerarin regulated the expression of pro-apoptotic proteins and caspase activation. ► Puerarin significantly inhibited the lead-induced apoptosis in rat kidney.