Mixture effects of three analgesics on biochemical indices in rat renal mitochondrial fraction

Humans are exposed to different mixtures of biologically active chemicals, unintentionally or intentionally for example by medications or through foods. The exposure risks of these chemical combinations are far from being understood.  According to the World Health Organization, evidence has shown that chemicals without action at individual levels may act additively and cause problems. Thus, human exposure to a mixture could produce biological responses which may not be predictable when used as single compounds. Drug combination is a common intervention in pain management, especially in patients with comorbidities and complex pain syndromes.  Aspirin, caffeine and paracetamol combination has been used in pain management but their toxicological implications have not been clearly worked out. The widespread use of analgesics such as paracetamol, aspirin and indomethacin for pain management has raised concerns about their potential adverse effects, particularly on vital organs such as the kidneys. This study aimed to investigate the mixture effect of three commonly prescribed analgesics on the kidney mitochondrial fraction of Sprague Dawley rats. They were orally exposed in 2 mL water to aspirin, paracetamol and indomethacin singly and in combination at their respective therapeutic doses daily for 14 days.  The control rats received water and food only. Certain biochemical parameters were assessed in the rats’ kidney mitochondrial fraction by spectrophotometric techniques. The statistical analysis of data was done using Graphpad prism software. Data were expressed as Mean ± SEM. The means were subjected to one-way analysis of variance using Tukey as a post-hoc analysis. Values were considered statistically significant at p<0.05. The activity of the superoxide dismutase under the Mix (drug combination group) increased significantly when compared with the respective enzyme activity under the individual drugs. Extent of lipid peroxidation, concentrations of non-protein sulphydryl (NPSH) and creatinine were lower in the Mix group relative to the test groups. Aspirin group recorded the least lipid peroxidation and NPSH concentration while indomethacin group the highest. The highest creatinine concentration was recorded among rats dosed paracetamol. The pro-oxidant ability of the drugs and hence renal toxicity appear to be in the order Paracetamol ˃ Indomethacine ˃ Combination dose ˃ Aspirin. Aspirin effect and presumably mechanism of its toxicity may be antagonistic to the activity of the rest of the drugs.  These findings indicated that the drug mixture was less pro-oxidant than the individual drugs at their therapeutic doses in the rat kidney.