Effects Of Urtica Dioica And Cimetidine® On Liver Function Following Acetaminophen Induced Hepatotoxicity In Mice

ABSTRACT

Acetaminophen is amongst the most widely used over the counter analgesic and antipyretic agent. Its acceptance is attributed to its efficacy and a high safety margin. An oral dose of 325-650 mg/kg is recommended for use. However, over dosage is responsible to half of the reported cases of acute liver failure. So there is need to explore on alternative therapy as the current treatment using N-acetyl cysteine is encountered with severe side effects such as seizures, intracranial hypotension, and cerebral oedema. Studies have demonstrated that Urtica dioica promotes regeneration of the liver cells following damage by carbon tetrachloride and aflatoxin B1. However, there is no published data on the same on acetaminophen toxicity. The aim of this study was to examine the effects of Urtica dioica on liver function following acetaminophen overdose in mice. Eighty mice comprising of an equal number of males and females were divided into the following eight groups of ten each: Control; Urtica dioica 450 mg/kg; acetaminophen 250 mg/kg; acetaminophen 500 mg/kg; Urtica dioica + acetaminophen 250 mg/kg; Urtica dioica + acetaminophen 500 mg/kg; acetaminophen 250 mg/kg + cimetidine 400 mg/kg and acetaminophen 500 mg/kg + cimetidine 400 mg/kg. Urtica dioica was administered as a single dose orally for 4 days, while acetaminophen and cimetidine was administered IP on day 4. Mice were bled by the tail for hematological assessment and euthanized 6 hours post-treatment, blood was collected via cardiac puncture for biochemical analysis and the liver harvested. Compared to the control, acetaminophen at 250mg/kg and 500 mg/kg was found to significantly reduce (p < 0.05) the RBC, neutrophils and albumin values while MCH, lymphocytes, ALT, AST, PT and liver pathology were increased as follows: RBC (8.08 x 1012/L vs 4.77 x 1012/L; 4.85 x 1012/L), MCH (13.60 pg vs 16.16 pg; 15.98 pg), neutrophils (30% vs 27.90%; 27.80%), lymphocytes (51.6% vs 54.80%; 54.60%), ALT (62.22U/L vs 305.20 U/L; 349 U/L), AST (313.78 U/L vs 707.4 U/L; 940 U/L), PT (12.30 seconds vs 15.70 seconds; 18.10 seconds), albumin (30.40 mg/ml vs 22.60 mg/ml; 18.30 mg/ml) and liver pathology (0 vs 2.6; 3.8). Acetaminophen at 500 mg/kg significantly increased the ALP (4.6 U/L vs 15.80 U/L), and total bilirubin (11.94 μmol/L vs 30 μmol/L). Even after exposure to acetaminophen toxicity mice pre-treated with Urtica dioica retained the following parameters within normal levels: neutrophils, lymphocytes, ALT, and liver integrity. Mice co-treated with the drug cimetidine even performed better than Urtica dioica in that all parameters were within normal levels except for AST in the group of mice treated with acetaminophen dose at 500 mg/kg. These results suggest that Urtica dioica and cimetidine are hepatoprotective and have potential in the management of acetaminophen toxicity. Confirmation of these findings through a clinical trial therefore offers an alternative approach for the management of acetaminophen toxicity.