Hepatoprotective and Toxicological Assessment of Spondias Mombin L. (Anacardiaceae) in Rodents

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Spondias mombin L. aqueous leaf extract is claimed by some Ghanaian herbalists to be traditionally useful in the management of hepatitis related jaundice. Its role in the management has however not been validated. The extract is also traditionally used in the treatment of various ailments but there is little data on its safety or otherwise. The objectives of this study were to assess the possible hepatoprotective effect of the extract on carbon tetrachloride (CCl4) - induced hepatotoxicity and to assess the possible general toxicity of the plant, in rodents. The hepatoprotective assessment was determined biochemically (using Liver Function Test, LFTs), morphologically (histopathological) and functionally (using Pentobarbitone-induced sleep time) in rodents. In general toxicological assessment, the effects of the extract on haematological, biochemical, morphological and in organo-body ratio assessment were performed. The extract was found to possess profound therapeutic ability as it decreased bilirubin levels from 5.2±0.1 µmol/L in the group treated with CCl4 only to 4.2±0.5 µmol/L in the group that received CCl4 and 1000 mg/kg of extract. Additionally, alanine aminotransferase (ALT) levels decreased from 219.7±30.02 U/L in CCl4 only treated group to 40.25 ± 2.39 U/L in groups treated with CCl4 and 1000 mg/kg respectively. This effect was clearly evident in histopathological studies of livers of rats. The therapeutic ability of the aqueous extract was comparable to Silymarin, a standard hepatoprotective agent. The extract was also found to be effective in both prophylactic and concomitant administrations. Pentobarbitone (50mg/kg body weight) challenged rats that received 100-1500mg/kg of extract after liver injury had minimum sleeping times recorded. The extract shortened the pentobarbitone-induced sleeping time to 333.6 ± 18.3 minutes in groups treated with CCl4 and 1500 mg/kg body weight, compared to 490.6 ± 36.9 minutes in CCl4 only treated group. This reduction was comparable to the control (316.6 ± 28.2 minutes), and more significant than in the group that received CCl4 and Silymarin (432.6±42.0 minutes). Acute toxicity studies preliminarily carried out on the aqueous extract revealed no lethality. With the exception of food intake (that dose-dependently increased), no physical, physiological and behavioural effects on mice were observed in the study. The LD50 of the aqueous extract was found to exceed 5000 mg/kg body weight. Sub-acute toxicity studies on the extract also showed no significant physical, physiological and behavioural effects. Haematological and biochemical studies also revealed no effect on rats administered with doses from 300 mg/kg to 1500 mg/kg body weight of extract. This effect was clearly confirmed by histopathological studies, as they showed no pathological difference in the target organs, livers and kidneys of treated rats when compared to those of the control rat group. It is concluded that the aqueous leaf extract of Spondias mombin is safe at doses of 50-1500mg/kg in rats and mice. It is also hepatoprotective against CCl4 induced liver damage. This hepatoprotective ability should have a role in the traditional use of the extract in the management of hepatitis related jaundice.
A thesis submitted in fulfilment of the requirements for the degree of Master of Philosophy, 2010