Effects of Paracetamol on the Liver and Kidney Functions of a Rat Model Following Prolonged Alcohol Administration

Abstract

Alcohol is a widely used psychoactive drug that is safe when consumed moderately. However, overindulgence results in hangover and multiple organ injury. On the other hand paracetamol is a non-steroidal anti-inflammatory drug that is widely used for management of pain and fever. At therapeutic doses, the drug is well tolerated, however, overuse is associated with hepatotoxicity. Due to its safety and efficacy, paracetamol is widely misused in management of hangover among regular consumers of alcohol. In spite of the potential health risks of the combined use of the two drugs, there is limited scientific data on their interaction. This study was therefore conceived with the aim to provide clarity on the effects of the interaction of the two drugs on the biological systems in a rat model. The animals were divided into twelve groups. The negative and positive controls received distilled water and alcohol, respectively. Alcohol was administered at 2.5, 3.5 and 4.5 g/kg orally for 4 weeks. While paracetamol was given at doses of 40 and 400 mg/kg. Half of the groups received combined doses of the two drugs. Hematological and blood chemistry were determined using auto-analyzers while histostructure was scored under light microscopy. The output data was analyzed using Minitab software. Comparison of weight, hematological and biochemistry values were done using one way ANOVA followed by Tukey’s test as the post hoc test. Alcohol and paracetamol caused changes in the physical characteristics of rats but the effect was non additive. In the case body weight, alcohol induced a dose and time dependent gain but for the combined drugs the effect was mixed. Conversely, alcohol and paracetamol did not affect (p > 0.05) the hematological profiles of the experimental animals and by extension had no influence on the bone marrow and immune system activity. In analyses of blood chemistry, the drugs resulted in a dose dependent elevation of liver enzymes, bilirubin, urea, reduced albumin levels and various degrees of liver and renal pathology. Thus, in moderate doses, paracetamol is safe, but high doses of the drug and chronic use of alcohol is hepatotoxic. It is as well inferred that AST/ALT index is a more predictive tool for alcohol exposure and liver injury since all alcohol treated groups had ratios above the normal value. Individually alcohol and paracetamol had a low risk of renal damage but when used together the risk is increased. In conclusion, heavy use of alcohol and regular use of paracetamol in management of alcohol induced hangover are discouraged as this can increase the risk of liver and kidney diseases.