Protective effects of chitosan oligosaccharide on paraquat-induced nephrotoxicity in rats

We investigated the apoptotic pathway during paraquat (PQ)-induced nephrotoxicity as well as renoprotective effects of chitosan oligosaccharide (COS) in male Sprague-Dawley rats because increasing evidences suggest that antioxidants may prevent PQ-induced apoptosis. Animals were pretreated with normal saline or COS (500 mg/kg, p.o.) 3 days before PQ (60 mg/kg, i.p.) administration, and were sacrificed at scheduled times after PQ administration. Rats administered PQ showed increased serum PQ concentrations, blood urea nitrogen, and creatinine levels in a time-dependent manner and creatinine clearance was decreased compared with control rats. All of these parameters were reversed significantly by COS pretreatment. After the PQ injection, cell deaths occurred in the proximal renal tubules with increased APE, PUMA, and cleaved caspase-3 expression, while APE and cleaved caspase-3 were immunolocalized mainly in the proximal tubules of control kidneys. COS-pretreated rat kidneys showed increased expression of the above parameters before PQ injection. APE and cleaved caspase-3 were immunolocalized ubiquitously in the renal cortex of COS-pretreated rats until 24h after the PQ injection. These results showed that PQ-induced nephrotoxicity may be caused by apoptosis in rat kidneys and that COS could protect kidneys from PQ-induced toxicity in association with the basal higher level of APE.