Omid Farshad
1 
, Mohammad Mehdi Ommati
2, Jale Yüzügülen
3, Akram Jamshidzadeh
1,4, Khadijeh Mousavi
4, Zahra Ahmadi
3, Negar Azarpira
5, Hasti Ghaffari
6, Asma Najibi
4, Marzieh Shafaghat
4, Hossein Niknahad
1,4, Reza Heidari
1* 1 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz Iran.
2 College of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi 030801, Peoples’ Republic of China.
3 Eastern Mediterranean University, Faculty of Pharmacy, Famagusta, North Cyprus, Turkey.
4 Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
5 Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
6 Department of Veterinary Sciences, Islamic Azad University, Urmia Branch, Urmia, Iran.
Abstract
Background: Cholestatic liver disease primarily affects hepatic tissue. Cholestasis could also influence the function of other organs rather than the liver. Cholestasis-induced kidney injury is a severe clinical complication known as “cholemic nephropathy” (CN). Bile duct ligation (BDL) is a trustworthy experimental model for inducing CN. Although the precise mechanism of renal injury in cholestasis is not fully recognized, several studies revealed the role of oxidative stress in CN. There is no promising pharmacological intervention against CN. Carnosine (CAR) is a peptide extensively investigated for its pharmacological effects. Radical scavenging and antioxidative stress are major features of CAR. The current study aimed to evaluate the role of CAR supplementation on the CN.
Methods: CAR was administered (250 and 500 mg/kg, i.p) to BDL rats for 14 consecutive days. Urine and serum markers of renal injury, biomarkers of oxidative stress in the kidney tissue, and renal histopathological alterations were monitored.
Results: Significant elevation in oxidative stress biomarkers, including ROS formation, lipid peroxidation, oxidized glutathione (GSSG) levels, and protein carbonylation were found in the kidney of BDL rats. Moreover, renal tissue antioxidant capacity and reduced glutathione (GSH) levels were significantly decreased in the organ of cholestatic animals. Renal histopathological changes, including tubular atrophy, interstitial inflammation, tissue fibrosis, and cast formation, were detected in the kidney of BDL rats. It was found that CAR administration significantly protected the kidney of cholestatic animals.
Conclusion: The antioxidative properties of this peptide might play a fundamental role in its protective properties during cholestasis.