Modulation of Carbon Tetrachloride (CCL4) and Acetaminophen induced liver damage in rats by Morinda Lucida Benth. (Rubiaceae).

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Morinda lucida is a tropical West Africa rainforest tree also called Brimstone tree. The plant is employed in the traditional settings for the treatment of malaria and severe jaundice. The alcoholic leaf extract of the plant was investigated for its possible toxicity in experimental rats and its hepatoprotective activity against carbon tetrachloride and acetaminophen-induced liver damage, also in rats. Administration of Morinda lucida extract (MLE) (250, 500, 1000, 2000, and 4000 mg/kg) to rats daily for two weeks did not cause significant changes in most of the haematological parameters assessed between the MLE treated groups and the control except for a significant increase in the mean corpuscular volume (MCV) at the 250 mg/kg. Also, there were no significant changes in the biochemical parameters assessed as well as the body weight and the selected organ weights (heart, spleen, liver and kidney). In the pentobarbitone-induced sleeping time assessment, pentobarbitone at 50 mg/kg, administered one hour after the oral administration of MLE (250, 1000 and 4000 mg/kg) caused a dose dependent decrease (P < 0.05) in the rat sleeping time. The hepatoprotective effect of the extract was assessed using two widely used models, CCl4 and acetaminophen. Intraperitoneal administration of CCl4 to rats caused severe liver damage as was indicated by the elevation of serum enzymes, bilirubin levels as well as the reduction in the protein levels. These effects were attenuated by the pre and post treatments with MLE and the effects were comparable to that of silymarin, used as the positive standard drug. A histopathology study of the liver samples from the MLE treated rats showed recovery from the injury caused by CCl4 to the toxin control group of rats whereas samples from the CCl4 did not. In the acetaminophen-induced liver damage, the effect of a single dose and multiple doses of the acetaminophen caused extensive liver damage, resulting in the elevation of the serum enzymes, bilirubin and a decrease in protein levels as well as damage to the hepatocytes as seen in the histopathology of the liver. Treatment with MLE assuaged this injurious effect caused by pre- and post-administration of acetaminophen by reducing the levels of the serum enzymes and bilirubin levels as well as increasing the protein levels. This effect was comparable to silymarin the standard positive drug used in the study. Overall, this study has shown that leaves of Morinda lucida is safe up to a dose of 4000 mg/kg in rats, does not interfere with the normal functioning of the hepatic microsomal drug metabolizing enzymes (MDME) and also protects the liver from injury caused by CCl4 and acetaminophen.
A Thesis submitted to the School of Graduate Studies, Kwame Nkrumah University of Science and Technology, Kumasi, in partial fulfilment of the requirements for the Degree of Master of Philosophy in Pharmaceutical Sciences, November-2011