α-Lipoic Acid Protects against Cyclosporine A-Induced Hepatic Toxicity in Rats: Effect on Oxidative Stress, Inflammation, and Apoptosis

Abstract: 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 (caspase3) 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.