| Autor: |
El-Mancy EM; Deanship of Common First Year, Jouf University, P.O. Box 2014, Sakaka 42421, Saudi Arabia.; Zoology Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo 11511, Egypt., Elsherbini DMA; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, P.O. Box 2014, Sakaka 42421, Saudi Arabia.; Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt., Al-Serwi RH; Department of Basic Dental Sciences, College of Dentistry, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia., El-Sherbiny M; Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia., Ahmed Shaker G; Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt., Abdel-Moneim AH; Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.; Department of Medical Physiology, Faculty of Medicine, Qassim University, Buraydah 51452, Saudi Arabia., Enan ET; Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt., Elsherbiny NM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia.; Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. |
| Abstrakt: |
The clinical application of cyclosporine A (CsA) as an immunosuppressive agent is limited by its organ toxicity. We aimed to evaluate the effectiveness of α-lipoic acid against CsA-induced hepatotoxicity and to delineate the underlying molecular mechanisms. Male Wistar rats (n = 24, 8 per each group) received the vehicle, CsA (25 mg/kg) and/or ALA (100 mg/kg, p.o.) for 3 weeks. Biochemical markers of liver function (serum ALT, AST, ALP < GGT), oxidative stress (MDA, TAC, SOD, GSH, Nrf2/HO-1), inflammation (NF-κB, CD68, iNOS, NO, COX-2), and apoptosis (caspase-3) were assessed in serum and tissue. Liver histological analysis using H&E and Sirius red was performed. The development of liver injury in CsA-treated animals was indicated by elevated levels of liver enzymes, oxidants/antioxidants imbalance, inflammatory cells infiltration, up-regulated expression of inflammatory mediators, and apoptosis. These changes were associated with altered architecture of hepatic cells and fibrous connective tissue. ALA co-administration protected against CsA-induced liver damage and ameliorated biochemical changes and cellular injury. In conclusion, ALA demonstrated hepatoprotective potential against CsA-induced liver injury through combating oxidative stress, inflammation, and apoptosis, highlighting ALA as a valuable adjunct to CsA therapy. |
