Abstract
BackgroundDrug-induced liver injury is a major health problem that challenges not only health care professionals but also the pharmaceutical industry and drug regulatory agencies. The possible hepatoprotective effect of the administration of mulberry ethanolic extract (MUL) leaves against hepatotoxic effect of the anti-rheumatic drug, methotrexate (MTX) was evaluated in this study both vivo (using animal models) and in vitro (human hepatoma HepG2 cells).MethodsIn the in-vivo study, 20 male albino rats were equally assigned into four groups; control group received distilled water orally; MUL treated-group received 500 mg/kg/day of MUL extract; MTX treated-group was injected with a single dose of 20 mg/kg MTX intraperitoneally on the 4th day; MUL-MTX treated-group received the previously mentioned doses of MUL and MTX (both control and MUL treated groups were administered a single dose of a physiological saline i.p.). At the end of the experimental period (14 days) activities of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) as well as total serum protein (TP) and albumin (ALB) levels were evaluated to assess liver function.ResultsA marked reduction in the viability of HepG2 cells was observed after 48 h with IC50 equal to 14.5 μg/mL of MUL administration. Treating the animals with MUL in combination with MTX mitigated liver injury, causing a significant reduction in activities of AST, ALT, ALP and LDH as compared to the MTX-group. The liver architecture revealed more or less normal appearance with the combined treatment when compared with MTX treatment alone.ConclusionsThis study recommends that the co-administration of MUL with MTX that may have therapeutic benefits against MTX-hepato-cytotoxicity.
Highlights
Drug-induced liver injury is a major health problem that challenges health care professionals and the pharmaceutical industry and drug regulatory agencies
Preparation of the plant extracts Plant material was collected from mulberry trees which cultivated in Faculty of Science, Suez Canal University, Ismailia, Egypt, in March 2014 and were identified and authenticated by Botany Department, Faculty of Science, Suez Canal University on the basis of taxonomic characters and by direct comparison with the herbarium specimens with a voucher number (HERBFAS#5) available at the herbarium of Botany department
The histopathological scoring analysis was performed according to Lobenhofer et al [23], the assessment was expressed as the sum of the individual score grades from 1, 2, 3, to 4 for each of the following parameters from liver sections: hepatocyte necrosis, fibrosis, cellular infiltration, hepatocyte apoptosis and hepatocyte fatty change
Summary
Drug-induced liver injury is a major health problem that challenges health care professionals and the pharmaceutical industry and drug regulatory agencies. The possible hepatoprotective effect of the administration of mulberry ethanolic extract (MUL) leaves against hepatotoxic effect of the anti-rheumatic drug, methotrexate (MTX) was evaluated in this study both vivo (using animal models) and in vitro (human hepatoma HepG2 cells). The drug-induced injury could be induced through different ways including direct toxic effect; immunological reaction or through active metabolite that is formed by the drug [2]. Methotrexate (MTX) drug, a structural analogue of folic acid, is widely used as anti-an rheumatic, cytotoxic chemotherapeutic agent for malignancies as well as in the treatment of various inflammatory diseases [3, 4]. Morus nigra (Moraceae) is widely distributed in Asia, Africa, Europe, and America, and it is commonly known as black mulberry.
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