Background: Paracetamol is well known analgesic and antipyretic drug. It is used as over the counter drug throughout the world. Prolonged use of paracetamol in higher doses is associated with severe risk of hepatotoxicity. Paracetamol induces oxidative stress in liver, which mimic the generation of free radicals, inflammatory prostaglandins, and cytokines. The documented antidote for paracetamol in clinical practice is N-acetylcysteine, which acts as an endogenous antioxidant.  N-acetylcysteine is associated with several adverse effects, and it can induce reverse effects on glutathione and ultimately produce toxicity. Therefore, we aim to evaluate the effects of Orthocetamol, as 2-Actamidophenol and used against paracetamol toxicity instead of N-acetylcysteine.

Methods and findings: In the current research work, orthocetamol was analyzed as an antidote against paracetamol toxicity. The hepatoprotective and toxicological effects of orthocetamol in different doses were evaluated using both pre-treated and post treated parameters with drug induced hepatotoxicity by standard paracetamol. Furthermore, the lethal dose toxicity of orthocetamol was also analyzed. The biochemical and histopathological methods were performed using standard protocols including liver function test as biochemical findings and using H & E staining methods for histopathological findings for liver. It was found that orthocetamol has antidote potential against paracetamol induced oxidative stress. It was also found effective in minimizing the toxic effects of paracetamol in both pretreated and post-treated group animals. Furthermore, it was found non-hepatotoxic in its lethal doses.

Conclusion: Orthocetamol suitable alternative to N-Acetyl cysteine in paracetamol induced hepatotoxicity.

Key words: Antipyretic, Paracetamol toxicity, Antidote, Orthocetamol