Protective effect of mycophenolate mofetil against nephrotoxicity and hepatotoxicity induced by tacrolimus in Wistar rats

Autor: Amira El Arem, Abedellatif Achour, Salwa Abid, Hassen Bacha, Imen Boussema-Ayed, Aicha Bouraoui, Hanen Ferjani
Rok vydání: 2016
Předmět:
Male
Physiology
Calcineurin Inhibitors
030232 urology & nephrology
chemical and pharmacologic phenomena
030204 cardiovascular system & hematology
Pharmacology
Kidney
Protective Agents
medicine.disease_cause
Biochemistry
Tacrolimus
Nephrotoxicity
Protein Carbonylation
Random Allocation
03 medical and health sciences
chemistry.chemical_compound
IMP Dehydrogenase
0302 clinical medicine
stomatognathic system
Animals
Medicine
Renal Insufficiency
Enzyme Inhibitors
Rats
Wistar
Dose-Response Relationship
Drug
business.industry
General Medicine
Mycophenolic Acid
Malondialdehyde
Calcineurin
Oxidative Stress
stomatognathic diseases
medicine.anatomical_structure
Liver
Hepatoprotection
chemistry
Toxicity
Chemical and Drug Induced Liver Injury
business
Biomarkers
Immunosuppressive Agents
Oxidative stress
DNA Damage
Zdroj: Journal of Physiology and Biochemistry. 72:133-144
ISSN: 1877-8755
1138-7548
Popis: Tacrolimus (TAC), a calcineurin inhibitor (CNI), is clinically used as an immunosuppressive agent in the transplant recipient; however, the use of TAC is greatly limited by its nephrotoxicity and hepatotoxicity. Mycophenolate mofetil (MMF), an inhibitor of the purine synthesis, has been used in combination with many immunosuppressive drugs such as TAC. The association TAC/MMF was used in organ transplantation to increase the efficiency and reduce acute rejection rates, but the effects of MMF on TAC-induced kidney and liver injuries are still not well investigated. The aims of this study are to explore whether MMF co-administration with TAC has a renoprotective and hepatoprotective effect against TAC-induced renal and hepatic injuries and to check the implication of oxidative stress in the MMF's possible protective effect. Our results showed that MMF (at 50 mg kg(-1) body weight (b.w.)) restored creatinine, in addition to increased AST and ALT levels by TAC (at 60 mg kg(-1) b.w.). Furthermore, MMF decreased DNA damage induced by TAC in the kidney and liver of rats as assessed by comet assay. This renoprotective and hepatoprotective effect of MMF was associated with an antioxidant effect. In fact, MMF co-treatment with TAC decreased oxidative damage induced by TAC. It reduced malondialdehyde (MDA) and protein carbonyl (PC) levels as well as catalase and superoxide dismutase (SOD) activities. We conclude that the co-administration MMF with TAC protect liver and kidney against TAC toxicity via an antioxidant process.
Databáze: OpenAIRE
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