Evaluation of acute toxicity of genabilic acid (menbutone 10%) in rabbits
World Rabbit Science
A complete investigation of the acute toxicity of a choleretic compound, menbutone, was performed in rabbits, including lethal dose for 50% of rabbits determination, clinical signs observation and in vivo and post-mortem examinations. Haematological, biochemical and histopathological changes resulting from intramuscular injection of menbutone were also investigated at dose 400 mg/kg body weight. Acute toxicity of menbutone at dose of 400 mg/kg BW induced interstitial myocarditis and multifocal
... tis and multifocal necrosis, whereas serum creatine phosphokinase, creatinine phosphokinase-MB isoenzyme and aspartate aminotransferase activities were significantly increased. Elevation of serum alanine aminotransferase and alkaline phosphatase activities and total bilirubin level associated with lowered albumin content was consistent with histopathological changes of hepatic tissues; hepatic necrosis and fatty infiltration were pronounced indicators of injuries. Renal tubular necrosis and interstitial nephritis were also observed in intoxicated rabbits. Menbutone also induced variations in some haematological parameters. We concluded that acute toxicity of menbutone in rabbits occurred at accidental high doses, as the lethal dose was about 50 fold over the recommended therapeutic dose for other animals. Cardiac muscle, liver and kidneys are the main target organs for menbutone toxicity. Menbutone is not recommended for use in rabbits suffering from any cardiac and hepatic disorders, especially in overdosing situations. Genabilic acid is a white, odourless and tasteless powder which is soluble in water and alkaline solution. Chemically, it is diethanolamine salts of 4, 4-methoxynaphthalene-1-(4) oxybutyric acid and provided as menbutone 10%. In veterinary practices, menbutone was used as a choleretic and appetiser drug for the treatment of digestive disorders in bovine, ovine, porcine and equine species (Symonds, 1982; Bishop, 2005). Menbutone was also used as an additional treatment in some cases of toxicity, such as calves intoxicated with sodium monensin due to feeding concentrate containing sodium monensin. The calves exhibited severe oedema, hydrothorax, hydropericardium, pulmonary oedema, enlargement of heart and dilated ventricles with fatty degeneration, followed by sudden death. The calves treated with mixture of oral administration of sodium carbonate (1 g/L), intravenous (i.v.) saline solution (3 L/animal d), intramuscular (i.m.) injection of genabilic acid (menbutone 5 mg/kg) and sorbitol (25 mg/kg) showed a recovery from intoxication (De La Cruz-Hernández et al., 2012) . In rats, gastrointestinal absorption of 14 C-menbutone is complete as, 50-60% of the administered dose is eliminated via the urine after 4-8 h, while 79% is excreted via the urine and 4.4% via the faeces after 24 h (Lund and Lassen, 1969). To our knowledge, there are no available data regarding the use of menbutone in rabbits and this may be related to the absence of toxicological evaluation of this drug in this species. Therefore, the present study aimed to evaluate the acute toxicity of menbutone in rabbits after single intramuscular injection and also to assess the haematological, biochemical and histopathological changes after drug injection.