PROOXIDANT-ANTIOXIDANT BALANCE IN LIVER OF RATS AFTER ADMINISTRATION OF IMMUNOSUPRESSANT MYCOPHENOLATE MOFETIL
Abstract
Background. The growth of immunodeficiency, unclearness of pathogenesis necessitates the reproduction of experimental immunosuppression in laboratory animals.
Objective. To study the prooxidant-antioxidant equilibrium in rat liver after the administration of immunosuppressant mycophenolate mofetil (MMF).
Materials and methods. The activity of free radical processes in liver tissue was assessed by the content of lipid peroxidation products: diene (DC) and triene (TC) conjugates, malonic dialdehyde (MDA). The content of nonenzymatic and enzymatic AOC components was assessed by the level of α-tocopherol, retinol, reduced glutathione (GSH), ubiquinone (CoQ) and catalase activity.
Results. The administration of the MMF at a dose of 40 mg/kg daily for 7 days does not result in the accumulation of products of lipid peroxidation in the sample of liver tissue, which may be due to the active use of the lipophilic antioxidant components of the cell. In 7 days after discontinuation of the administration of the drug, complete restoration of prooxidant-antioxidant balance in liver is observed in animals. A two-week injection of MMF at a dose of 40 mg/kg daily results in the activation of the peroxidation of lipids in liver tissue that can lead to subsequent death of the hepatocyte underlying the drug-induced liver injury (DILI).
Conclusion. Intragastric administration of the MMF for 7 days at a daily dose of 40 mg/kg can be used for experimental modeling of immunodeficiency without development of signs of toxic damage to the liver by free radical origin, which occurs in the case of classical immunosuppressants.
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