الفهرس 
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Abstract
This study aimed to investigate whether carnosine (a natural dipeptide found in humans) and crocin (a natural product extracted from saffron and gardenia) can prevent the deleterious effects of AKI caused by glycerol-induced rhabdomyolysis with a focus on the role of Nrf2/HO-1 signaling pathway.
Acute kidney injury (AKI) was induced in rats by single intramuscular (IM) injection of glycerol. Thirty-six male Wistar albino rats will be divided into 6 groups with 6 rats in each group as follows:
• group 1 (Sham/Control): rats were injected by 0.9% saline (IP) for 7 days followed by a single IM injection of 0.9% saline, equally divided between both right and left hind limbs muscles on 8th day.
• group 2 (GLY/Diseased): rats were injected by 0.9% saline (IP) for 7 days followed by a single IM injection of 50% glycerol, equally divided between both right and left hind limbs muscles on 8th day.
• group 3 (CAR): rats were injected by carnosine (70 mg/kg, IP) for 7 days followed by a single IM injection of 0.9% saline, equally divided between both right and left hind limbs muscles on 8th day.
• group 4 (CAR + GLY): rats were injected by carnosine (70 mg/kg, IP) for 7 days followed by a single IM injection of 50% glycerol, equally divided between both right and left hind limbs muscles on 8th day.
• group 5 (CRO): rats were injected by crocin (200 mg/kg, IP) for 7 days followed by a single IM injection of 0.9% saline, equally divided between both right and left hind limbs muscles on 8th day.
• group 6 (CRO + GLY): rats were injected by crocin (200 mg/kg, IP) for 7 days followed by a single IM injection of 50% glycerol, equally divided between both right and left hind limbs muscles on 8th day.
All rats were administered either CAR (70 mg/kg, IP), CRO (200 mg/kg, IP), or 0.9% saline (IP) for 7 consecutive days, followed by a single intramuscular (IM) injection of either 50% glycerol (10 ml/kg) or 0.9% saline, equally divided between both right and left hind limbs muscles on 8th day.
On the ninth day (24 hours after the IM injection), blood samples were obtained from the eye in an EDTA-containing tube and centrifuged at 3000 rpm for 20 minutes at 4°C to obtain plasma. Rats were weighed, anaesthetized with a 60 mg/kg intravenous injection of sodium pentobarbital, and sacrificed by cervical dislocation. The kidneys and hind muscles were promptly collected and rinsed in cold 0.9 % saline, and the weights of the kidneys were recorded in order to construct the RSI. The RSI was computed by dividing the kidney weight (g) by the total body weight (g) and multiplying the result by 100. Cold PBS was applied to the left kidney. The right kidney was separated into two halves by cutting it vertically. The muscles were maintained in 10% NBF for histological evaluation, while the RNA was stored at -80 °C for gene expression analyses.
The current study determined creatinine, BUN, catalase activity, MDA, NO, TGF-β, myoglobin, KIM-1, CK-MM, and the gene expression of HO-1, Nrf2, and eNOS. In addition to the histopathological examination of muscle and kidney tissues.
Rhabdomyolysis was demonstrated by histopathological changes in muscle sections and elevated myoglobin levels in kidney tissue homogenate samples. Kidney injury was distinguished by an increase in creatinine, kidney injury molecule-1, malondialdehyde, and nitric oxide, as well as a decrease in catalase activity. Increased inflammatory indicators and histological changes in kidney sections were also observed as a result of the injury. Pretreatment with carnosine and crocin corrected all of these effects. Both drugs have the potential to increase HO-1 gene expression. Both treatments, however, failed to restore the decreased Nrf2 expression in glycerol-treated animals.