Abstract
BackgroundThe present study investigated the ameliorative effect of melittin, a major polypeptide in the venom of honeybee (Apis mellifera), on isoniazid-(INH) and rifampicin-(RIF) induced hepatotoxicity in male albino rats.MethodThirty rats (140-200 g) were divided into five groups (n = 6): normal control (NC) received normal saline orally (NaCl, 0.9%; toxic (T) group received INH + RIF (each rat received 100 mg/kg, p.o.); melittin (Mel15, Mel30) groups (each rat received 15 or 30 μg/kg s.c); and normal recovery (NR) group received INH + RIF (each rat received 100 mg/kg, p.o.). Blood and liver samples were collected for biochemical, hematological and histopathological studies respectively.ResultsThe administration of melittin was found to prevent the antitubercular drug-induced alterations in the diagnostic markers; reduced glutathione (GSH), direct bilirubin (DB), total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and total serum protein (TSP). Besides, hematological alterations were significantly high in Mel groups when compared to the toxic group. The NR group exhibited lower levels of DB, TB, ALP, LDH and TSP. In addition, treatment with melittin offered protection in the NR group with respect to MDA levels.ConclusionEvidence from this study suggests that melittin is beneficial for the prevention of acute hepatic failure in antitubercular drug-induced hepatoxicity and could be used as a potential therapeutic agent.
Highlights
The present study investigated the ameliorative effect of melittin, a major polypeptide in the venom of honeybee (Apis mellifera), on isoniazid-(INH) and rifampicin-(RIF) induced hepatotoxicity in male albino rats
A meta-analytical study on the co-administration of isoniazid (INH) and rifampicin (RIF), the first-line drugs used for tuberculosis therapy indicated that they are associated with 2–6% hepatotoxicity [2], acute liver injury and high mortality rate [3]
The T group showed a significant decrease 77.8% compared to the Normal control (NC) group, whereas, a significant increase of 75.18 and 88.25% was exhibited in Mel 15 and Mel 30 groups respectively compared to the T group (P < 0.05) (Table 1)
Summary
The present study investigated the ameliorative effect of melittin, a major polypeptide in the venom of honeybee (Apis mellifera), on isoniazid-(INH) and rifampicin-(RIF) induced hepatotoxicity in male albino rats. A meta-analytical study on the co-administration of isoniazid (INH) and rifampicin (RIF), the first-line drugs used for tuberculosis therapy indicated that they are associated with 2–6% hepatotoxicity [2], acute liver injury and high mortality rate [3]. These drugs mediate the generation of highly reactive oxygen species (ROS), which act as a trigger of lipid peroxidation and a means for destruction of the plasma membrane [4]. It increases INH induced toxicity by stimulating the formation of the toxic metabolite hydrazine via amidase pathway. Combination chemotherapy with INH-RIH was found to stimulate the conversion of INH to isonicotinic acid, another
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