Carnosine and crocin ameliorate oxidative stress in rats with rhabdomyolysis-induced acute kidney injury through upregulating HO-1 gene expression

Abstract

We aimed to investigate whether carnosine (a natural dipeptide found in humans) and crocin (a natural product extracted from saffron and gardenia) can prevent the harmful effects of acute kidney injury (AKI) caused by glycerol-induced rhabdomyolysis with a focus on the role of the nuclear factor E2-related factor-2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway. Thirty-six male Wistar rats were divided into 6 groups: 3 of them received saline, carnosine, and crocin IP for 7 days and the other 3 groups received the same treatment in addition to a single IM injection of 50% glycerol (10 ml/kg, divided between the two limb muscles) on 8th day. All animals were sacrificed after 24 h of the IM injection. Blood samples, muscles, and kidneys were collected for further investigations. Rhabdomyolysis was evidenced by the histopathological alterations in muscle sections and increased levels of myoglobin in kidney tissue homogenate samples. Kidney injury was characterized by increased creatinine, kidney injury molecule-1, malondialdehyde, nitric oxide, and decreased catalase activity. The injury also increased inflammatory markers and histopathological alterations in kidney sections. All these effects were corrected by pretreatment with carnosine and crocin. Both agents could also elevate HO-1 gene expression. However, both agents failed to restore the declined Nrf2 expression in glycerol-treated groups. Carnosine and crocin can effectively prevent rhabdomyolysis-induced AKI in rats through augmenting gene expression of HO-1 and antioxidant system and suppressing the generation of reactive oxygen species, lipid peroxidation, and inflammatory response.