Agmatine attenuates rhabdomyolysis-induced acute kidney injury in rats in a dose dependent manner

Acute kidney injury (AKI) is a serious disorder that accompanies rhabdomyolysis (RM). The underlying mechanisms as well as protective approaches need to be investigated. This study was targeted to explore the prophylactic effect of agmatine (AGM), an endogenous metabolite of L-arginine against RM-induced AKI. A rat model was elucidated by 50% glycerol (10 ml/kg, im). Glycerol induced functional and structural alterations in the kidney. Pretreatment with AGM significantly ameliorated RM through decreasing total creatinine kinase (CK) and creatine kinase-MB (CK-MB) levels. AGM alleviated functional changes evidenced by decreased serum levels of creatinine (Cr), blood urea nitrogen (BUN) and decreased urinary levels of albumin and proteins. Moreover, AGM decreased renal levels of malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL-1 beta), neutrophil gelatinase-associated lipocalin (NGAL), inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF-kappa B) and myeloperoxidase (MPO). Furthermore, AGM significantly increased renal levels of reduced glutathione (GSH), superoxide dismutase (SOD), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Structural abnormalities confirmed by histopathological examination were also attenuated. AGM confers a dose-dependent protection against RM-induced AKI by preventing muscle degradation, alleviating oxidative stress and inhibiting production of cytokines and inflammation.