Metformin and silymarin afford protection in cyclosporine A induced hepatorenal toxicity in rat by modulating redox status and inflammation.

Publisher: Wiley Country of Publication: United States NLM ID: 9717231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1099-0461 (Electronic) Linking ISSN: 10956670 NLM ISO Abbreviation: J Biochem Mol Toxicol Subsets: MEDLINE

Original Publication: New York, NY : Wiley, c1998-

Chemical and Drug Induced Liver Injury*/metabolism ; Chemical and Drug Induced Liver Injury*/prevention & control ; Kidney Diseases*/chemically induced ; Kidney Diseases*/metabolism ; Kidney Diseases*/prevention & control; Cyclosporine/*adverse effects ; Metformin/*pharmacology ; Silymarin/*pharmacology; Animals ; Cyclosporine/pharmacology ; Inflammation/chemically induced ; Inflammation/metabolism ; Inflammation/prevention & control ; Male ; Oxidation-Reduction/drug effects ; Rats ; Rats, Wistar

The use of cyclosporine A (CsA) as an immunosuppressive agent is often limited owing to its hepatotoxic and nephrotoxic properties. The present study was designed to evaluate the protective effect of metformin and silymarin in a rat model of CsA induced hepatorenal toxicity. The study included seven groups of Wistar albino rats (n = 6 per group): normal control, experimental control (CsA alone, 25 mg/kg), CsA + metformin (50 and 500 mg/kg), CsA + silymarin (50 and 200 mg/kg) and CsA + vitamin E (100 mg/kg). All the drugs were given daily for a period of 21 days by oral gavage and their effect was evaluated on serum levels of organ function markers (serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, bilirubin, urea/blood urea nitrogen, creatinine), markers of oxidative stress (thiobarbituric acid reactive substances, glutathione, superoxide dismutase), inflammation (nitrite, myeloperoxidase, tumour necrosis factor-alpha, prostaglandin E 2 ), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labelling positivity) in addition to tissue histology, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) immunoreactivity. Administration of metformin and silymarin along with CsA ameliorated functional damage to liver and kidneys in a dose-dependent manner. Significant and comparable improvement in the tissue levels of oxidative stress, inflammation, apoptotic markers was also observed following treatment with both the test drugs. Normalization of histology scores, as well as COX-2 and iNOS immunoreactivity scores, further strengthened these findings. The hepatoprotective and nephroprotective effects of metformin and silymarin were comparable and matched with that of reference drug, vitamin E. The findings of the present study suggest that both metformin and silymarin have a potential for clinical use in patients receiving long-term CsA treatment to maintain their liver and kidney functions.
(© 2020 Wiley Periodicals LLC.)

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Keywords: cyclosporine A; hepatotoxicity; inflammation; metformin; nephrotoxicity; oxidative stress; silymarin

0 (Silymarin)
83HN0GTJ6D (Cyclosporine)
9100L32L2N (Metformin)

Date Created: 20200904 Date Completed: 20210608 Latest Revision: 20210608

20231215

10.1002/jbt.22614

32886845