Hepatoprotective activity of liv-52 on rifampicin and isoniazid induced liver toxicity in adult albino rats (rattus norvegicus)

Abstract

Liver toxicity refers to injury to the liver due to drugs, chemical or environmental toxins. Rifampicin (RIF) and Isoniazid (INH) are two main medicinal drugs used as first line regimen in the treatment of Tuberculosis. These drugs have shown to induce hepatotoxicity upon administration. Liv-52, a polyherbal formulation has been shown to have clinical use in the treatment of several liver disorders in the recent years. However, there is deficiency in data regarding the histological and morphological effect of Liv-52 and the accurate dose required to prevent liver toxicity arising from INH and RIF induced liver toxicity. The broad objective was to evaluate the hepatoprotective activity of Liv-52 against of INH and RIF induced liver toxicity. The study was conducted at Zoology and Human Anatomy departments in Maseno University, Kisumu County, Kenya. Posttest-only experimental study design was adopted. Adult albino rats with an average weight of between 150g to 250g were used in the study. A total of 24 rats were randomly allocated into 4 groups each group containing 6 rats. The Albino rats were fed on normal rat pellets and water ad libitum. A negative control group with no intervention, an experimental group of; INH 50mg/kgbwt and RIF 50mg/kgbwt (positive control); INH 50mg/kgbwt, RIF 50mg/kgbwt and Liv-52 155mg/kgbwt(LD Liv-52); INH 50mg/kgbwt, RIF 50mg/kgbwt and Liv-52 207mg/kgbwt (HD Liv-52) orally daily. A 21 days, the albino rats were sacrificed humanely, liver harvested and weighed. Blood samples were taken from each group for estimation of liver serum biomarkers. Thereafter, the livers were processed and stained with Haematoxylin and Eosin for histological examination. Excel sheet was used to enter data which was later analyzed through SPPS version 25. One-way ANOVA with post hoc Bonferroni was used to compare the data obtained from experimental and control groups. Histomorphological data was described based on liver sections observed microscopically. Significance levels was P value less or equal to 0.05 (p≤ 0.05). The results was presented in images, tables, and figures. There was a significant (p value < 0.0001) decrease in gross morphometric measurements of the weight, length, width, thickness in positive at control compared to hepatoprotective groups. In the hepatoprotective group, there was a significant (p≤0.0001) increase in mean final body weight in HD Liv-52(207mg/kgbwt) and slight increase in LD Liv-52(155mg/kgbwt) groups at 236.31±.63 and 208.33±.83 respectively compared to 184.78±.78 in positive control(RIIH 50kg/kgbwt) group. Additionally, the mean liver weight in HD Liv-52 group was significantly (p≤0.0001) higher at 11.40±.21 compared to 9.197±.26 in positive control group. The means of the liver gross morphometric measures were observed to be increasing in both LD Liv-52 (155mg/kgbwt) and HD Liv-52 (207mg/kgbwt) hepatoprotective groups as compared to positive control (RIIH 50kg/kgbwt) group. That is length of 50.82±.23, width of 41.86±.23 and thickness of 0.39±.01 in LD Liv-52 and length of 54.25±.24, width of 44.68±17 and thickness of 0.50±.00 in HD Liv-52. The liver sections in positive control group showed deranged histomorphological features, partially deranged histomorphological features were observed in low dose Liv-52 at 155mg/kg/bwt group while those in high dose Liv-52 at 207mg/bwt showed normal histomorphological features. After administration of Liv-52, the three selected liver biochemical parameters (ALT, AST and ALP) were above their normal ranges. In conclusion, the gross morphometric and histomorphological changes on the liver among adult albino rats indicates that Liv-52 was able to prevent liver injury caused by rifampicin and isoniazid, therefore, its recommended that its pharmacokinetics and pharmacodynamics be evaluated for use in human patients on Rifampicin and Isoniazid treatment.