Evaluation of acute toxicity of genabilic acid (menbutone 10%) in rabbits
Keywords:menbutone, lethal dose, necrosis, rabbits
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 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.
AEPPAE. Naunyn-Schmiedeberg’s Archiv fuer Experimentelle Pathologie und Pharmakologie. Berlin, Germany, V.110-253, 1925-66. For publisher information, see NSAPCC. Volume (issue)/page/year: 222,244,1954
Bishop Y. 2005. The veterinary formulary, text book. 6th edition, Y. Bishop (ed.). 236.
Brent J.A., Rumack B.H. 1993. Role of free radicals in toxic hepatic injury II. Are free radicals the cause of toxin-Induced liver injury? Clin. Toxicol. 31: 173-196. doi:10.3109/15563659309000384
Cardinale D., Sandri M.T., Colombo A., Colombo N., Boeri M., Lamantia G., Civelli M., Peccatori F., Martinelli G., Fiorentini C., Cipolla C.M. 2004. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation, 109: 2749-2754. doi:10.1161/01.CIR.0000130926.51766.CC
Culling C.F. 1983. Handbook of Histopathological and Histochemical Techniques, 3rd ed. London, Boston: Butterworth.
De la Cruz-Hernández N.I., Argudín-Salomón O.A., Zertuche- Rodríguez J.L., Medellín-Ledezma J.A., Flores-Gutiérrez G.H. 2012. Case report: outbreak of sodium monensin intoxication in feedlot cattle from Mexico. Revue Med. Vet., 163: 60-63.
Hsu T.S., Chiang Y., Wang W., Chao P.T., Bao J.G., Wang Y. 2003. Pulse analysis as a possible real time biomarker complementary to SGPT and SGOT for monitoring acute hepatotoxicity. Toxicol. Mech. Methods, 13, 181-186. doi:10.1080/15376510309829
Lund J., Lassen J.B. 1969. Elimination and distribution of menbutone (Genabil®) in rats. Acta Pharmacol. Toxicol., 27: 429-438. doi:10.1111/j.1600-0773.1969.tb00490.x
Miserocchi G., Trippenbach T., Mazzarelli M., Jaspar N., Hazucha M. 1978. The mechanism of rapid shallow breathing due to histamine and phenyldiguanide in cats and rabbits. Respir Physiol., 32: 141-153. doi:10.1016/0034-5687(78)90105-6
Miserocchi G., Mazzarelli M., Quinn B., Mozes R.S. 1979. Histamine and phenyldiguanide induced tachypnea in hypercapnia and hypoxia. Respir. Physiol., 36: 217-229. doi:10.1016/0034-5687(79)90026-4
Pershin G.N. 1971. Methods of experimental chemotherapy: Practical guidance, 2nd edition, Moscow. Russia: Medicina.
Piyachaturawat P., Tubtim C., Chuncharunee A., Komaratat P., Suksamrarn A. 2002. Evaluation of the acute and subacute toxicity of a choleretic phloracetophenone in experimental animals. Toxicol. Lett., 129: 123-132. doi:10.1016/S0378-4274(02)00006-1
Symonds H.W., 1982. The choleretic effect of menbutone and clanbutin sodium in steers. Vet. Rec., 110: 423-425. doi:10.1136/vr.110.18.423
This journal is licensed under a "Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)".