The Histomorphological and biochemical hepatorestorative Effects of silymarin milk thistle on paracetamol induced Hepatotoxicity in adult albino rats (Rattus norvegicus)

Abstract

Liver toxicity has been on a steady rise worldwide and it is attributed to various causes including paracetamol-induced when taken singly in high dose or prolonged use. Paracetamol is a common, most preferred and widely tolerated first line analgesia for mild and moderate acute pain for all age groups. Since its cheap and easily accessible as an over-the-counter drug, it can be easily misused especially with increasing causes of pain in the society. Its long-term use causes liver toxicity and eventually liver failure. Most plant medicinal extracts have been found to either prevent or ameliorate the hepatotoxic effects either alcohol or drug induced. Silymarin milk thistle is a medicinal herb that grows widely in various climatic conditions, available locally and affordable to all. It has been used over time to prevent or treat liver diseases though there is inadequate data on its histo-morphologic restorative effects that occur on the liver following drug induced hepatotoxicity. This study aimed at evaluating the restorative histo-morphological changes of silymarin milk thistle on paracetamol induced hepatotoxicity. Specifically, the study determined; the histomorphological injurious effects that occur on the liver following toxicity, the restorative histomorphological effects of various doses of silymarin milk thistle on paracetamol hepatotoxicity and assessed the changes in liver biochemical parameters of Aspartate transaminase (AST), Alkaline phosphatase (ALP) and Alanine transaminase (ALT) following administration of silymarin milk thistle and paracetamol toxicity. A post-test only true experimental study design was used with a total of 24 adult albino rats randomly sampled into intervention and non-intervention groups. The non-intervention further into control of 3 rats received no drug interventions and 3 rats that received high dose of paracetamol (750 mg/kbwt) for 5 days. A total of 3 intervention groups each having 6 rats received same dose of paracetamol (750 mg/kbwt) for 5 days to induce hepatotoxicity and varying doses of silymarin (low dose- 200mg/kbwt, medium dose- 400 mg/kbwt and high dose- 600 mg/kbwt) to each group respectively for the remaining 16 days of the experimental process. Humane sacrificial was done on day 21 and liver tissues harvested and processed for both gross and histological examinations and stained using Hematoxylin & Eosin (H&E). Morphological data were entered into excel sheet, analyzed through Statistical Package for the Social Sciences (SPSS) version 26, and One-way Analysis of Variance (ANOVA) was used to test the mean groups and a post hoc was used to test the difference between the mean groups. The results showed that there was a significant reduction (P=0.0001) in length, width and volume in the control group as compared with the paracetamol only group. It also had areas of hemorrhagic necrosis, vacuolated hepatocytes and dilated sinusoids. Unlike the low dose and medium dose silymarin groups, there was a significant increase in all the parameters (volume, weight, length and width) in the high dose silymarin when compared with the control. In comparison with the control group the medium dose and low dose groups registered a significant difference in all the parameters while the high dose group showed no significant difference to signify some level of restoration. Histologically, the paracetamol only group liver had areas of hemorrhagic necrosis, pocket foci of hemorrhage and dilated sinusoids and compared with those of the low dose and medium dose silymarin groups. The high dose group had even distribution of normal hepatocytes and sinusoids and was similar with the control liver. The liver biochemical parameters were significantly (P=0.0001) elevated in the paracetamol only group, low dose and medium dose silymarin groups when compared with the control whose parameters presented no significant difference with those of the high dose silymarin group. In conclusion, high dose silymarin had hepato-restorative effects, therefore more studies should be done on the safe human dose and its pharmacokinetics so that it can be taken alongside those drugs causing hepatotoxicity and to treat liver related conditions, ultimately reducing liver related mortalities.