THE AMELIORATIVE EFFECT OF ACACIA SIEBERIANA D.C. METHANOL ROOT BARK EXTRACT ON INDUCED LIVER INJURY AND ITS SUBCHRONIC TOXICITY PROFILE IN RATS
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ABSTRACT
Acacia sieberiana D.C is traditionally used as a remedy for various ailments including hepatitis. The effect of methanol root bark extract of Acacia sieberiana (ASE) on paracetamol (PCM) - and bile duct ligation (BDL) –induced liver injury wereinvestigated in rats. Rats were divided into six groups (Groups I-VI) of 5 and 6 rats for PCM and BDL, respectively. For the PCM-induced liver injury study, animals were pre-treated with normal saline, silymarin (50mg/kg) and extract (250, 750, 1,500 mg/kg)for 7 days. After the last dose, liver injury was initiated by the administration of PCM (2g/kg). In BDL-induced liver injury study, 6 nonligated but operated rats were used as control (Group I), Groups I and II received normal saline while Groups III-VI received silymarin (50mg/kg), the extract (125, 250 and 380 mg/kg), respectively, for 7 days. At the end of the experiment, blood and organs were obtainedfor biochemical and histological assay. Results showed the presence of carbohydrates, glycosides, triterpenes, cardiac glycosides, saponins, tannins, flavonoids and alkaloids. The LD50 values for oral and intraperitoneal routes of ASE were >5,000 and 1,300 mg/kg respectively. The subchronic toxicity study revealed that ASE significantly (P<0.05) reduced body weight when compared to the control and significantly (P<0.05) elevated ALP, whereas, serum urea and blood lymphocytes were significantly (P<0.05) increased at the 1500mg/kg dose group. The histology of the heart revealed no effect. However, the liver produced a dose-dependent hepatocellular necrosis and vacuolations. There was also lymphocyte hyperplasia and glomerular necrosis of the kidneys and alveolar congestion of the lungs. PCM significantly (P<0.05) elevated ALT, AST, direct Bilirubin and significantly (P<0.05) decreased total protein and albumin when compared to ASE. Whereas, ASE at 250 and 750 mg/kg was seen to significantly (P<0.05) decrease the levels of ALT and AST, while xix total protein and albumin were significantly (P<0.05) elevated in ASE-treated groups. However, direct bilirubin was significantly (P<0.05) decreased in silymarin group and 750 mg/kg ASE group. Furthermore, PCM significantly (P<0.05) decreased SOD and increased MDA when compared with ASE pre-treated groups. The histology revealed, PCM caused severe necrosis of the hepatocytes with vascular and sinusoid congestions but the impacts were mild with silymarin and lower doses of ASE pre-treated groups. The BDL–induced liver injury study revealed that ASE significantly (P<0.05) decreased AST level at lower doses and significantly decreased ALP level at higher doses. Likewise, ASE significantly (P<0.05) decreased direct and total bilirubin levels in silymarin and ASE treated groups. There was significant (P<0.05) elevation of SOD at lower ASE doses while GPx and CAT were significantly (P<0.05) elevated in ASE-treated groups. Furthermore, MDA was only significantly decreased at 125 mg/kg ASE group. Histology revealed that themorphology of liver tissue was preserved at 125 and 250 mg/kg ASE groups from BDL-induced moderate necrosis and vascular congestion. The study concludes that Acacia sieberiana is relatively non-toxic with acute administration and has hepatoprotective potentials on PCM- and BDLinduced liver injury at its lower doses but could be relatively toxic at its higher doses and/with prolonged use.
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