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

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

Content Provider	MDPI
Author	El-Mancy, Eman M. Elsherbini, Dalia Mahmoud Abdelmonem Al-Serwi, Rasha Hamed El-Sherbiny, Mohamed Shaker, Gehan Ahmed Abdel-Moneim, Abdel-Moneim Hafez Enan, Eman T. Elsherbiny, Nehal M.
Copyright Year	2022
Description	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.
Starting Page	442
e-ISSN	23056304
DOI	10.3390/toxics10080442
Journal	Toxics
Issue Number	8
Volume Number	10
Language	English
Publisher	MDPI
Publisher Date	2022-08-02
Access Restriction	Open
Subject Keyword	Toxics Toxicology Cyclosporine A Liver Oxidative Stress Inflammation Apoptosis
Content Type	Text
Resource Type	Article

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