Effect of penehyclidine hydrochloride pretreatment on rhabdomyolysis-induced acute kidney injury in rats

Abstract

Objective To evaluate the effect of penehyclidine hydrochloride pretreatment on rhabdomyolysis-induced acute kidney injury (AKI) in rats. Methods Forty-two pathogen-free male Sprague-Dawley rats, weighing 200-220 g, aged 2 months, were randomly divided into 3 groups using a random number table: control group (group C, n=6), AKI group (n=18), and penehyclidine hydrochloride group(group PH, n=18). The model of rhabdomyolysis-induced AKI was established by injecting 50% glycerol 10 ml/kg into the lateral muscle of bilateral hindlimbs in AKI and PH groups.The equal volume of normal saline was given in group C. Penehyclidine hydrochloride 0.2 mg/kg was injected intraperitoneally at 30 min before administration of glycerol in group PH.Six rats were selected at 1 h after administration of normal saline in group C, or at 1, 6 and 24 h after administration of glycerol, blood samples were collected from the inferior vena cava for determination of the serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations by enzymic colorimetric method.The animals were sacrificed, and kidney specimens were obtained for pathologic examination and for determination of the expression of DJ-1 and phosphatase tensin homolog deleted on chromosome 10 (PTEN) encoding protein (by immuno-histochemistry and Western blot). The damage to the renal tubules was scored. Results Compared with group C, the serum BUN and Cr concentrations and renal tubular damage score were significantly increased, the expression of DJ-1 was down-regulated, and the expression of PTEN protein was up-regulated in group AKI (P<0.05 or 0.01). Compared with group AKI, the serum BUN and Cr concentrations and renal tubular damage score were significantly decreased, the expression of DJ-1 was up-regulated, and the expression of PTEN protein was down-regulated in group PH (P<0.05 or 0.01). Conclusion Penehyclidine hydrochloride pretreatment can reduce rhabdomyolysis-induced AKI probably by up-regulating the expression of DJ-1 and down-regulating the expression of PTEN protein in rats. Key words: Cholinergic antagonists; Rhabdomyolysis; Kidney failure, acute