Hepatoprotective effect of a polyherbal formulation and ascorbic acid in paracetamol induced hepatic damage in rabbits

Background: The hepatoprotective effect of a polyherbal formulation was evaluated in female rabbits. The herbal formulation was used alone and in combination with ascorbic acid (AsAc) in animals with paracetamol (ParCM)-induced hepatic damage. Methods: The study design included five groups, each comprised of five animals. Group A was the control group (untreated; given only routine diet) while group B was given a single oral dose of ParCM (2 g/kg) on day 9. Groups C, D and E were pretreated with polyherbal formulation (PoHF; 500 mg/kg), ascorbic acid (AsAc; 200 mg/kg) and PoHF (500 mg/kg) combined with ascorbic acid (AsAc; 200 mg/kg), respectively for 9 consecutive days. On the last day (day 9), after 30 minutes of routine treatments, a single dose of ParCM (2 g/kg) was administered in groups C, D and E. Animals were sacrificed 24 hours after the last treatment. Blood and liver samples were collected from all animals. Serum was separated from the blood samples and subjected to biochemical tests for liver biomarker analysis. The biomarkers included alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin. Elevation of enzyme markers was considered an indicator of hepatocellular injury. Results: Serum levels of liver enzymes and total bilirubin were elevated significantly in group B when compared to group A. The level of serobiochemicals significantly dropped in group C but increased significantly in group D, as compared to group B. No statistically significant effect on liver enzymes was observed in group E when compared to group B. Groups D and E showed a significantly higher level of serological parameters as compared to group C. The biochemical findings were further corroborated with histopathological analyses of the liver tissue samples. Histopathological examination of the livers of rabbits in group A showed normal hepatic cell architecture. However, groups B and D revealed severe congestion of the central vein and sinusoids, periportal fibrosis and infiltration of inflammatory cells; these parameters were of mild and mostly moderate severity in groups C and E, respectively. The histopathological findings strongly supported the results of the biochemical analyses. Conclusion: Thus, our study herein demonstrates that herbal formulation remains an effective means to ameliorate ParCM-induced elevation of serum biochemical parameters and changes to the liver histology. Ascorbic acid induced deteriorating effects in a ParCM-intoxicated rabbit animal mode. Moreover, combination of herbal product and ascorbic acid failed to yield liver protecting effects in ParCM-poisoned animals. The damaging effects of ascorbic acid might be attributed to its pro-oxidant attitude, as reported by many research studies. To expand on these findings further studies are warranted, including evaluating other hepatotoxicity inducers (besides ParCM), testing different doses of ascorbic acid and ParCM, and testing a greater number of animals along with other animal models.