HEPATOPROTECTIVE EFFECT OF MELATONIN ON PARACETAMOL INDUCED HEPATOTOXICITY IN ALBINO RATS
Keywords:Drug-induced liver injury, hepatotoxicity, paracetamol, N-acetyl cysteine, melatonin
Objective: Liver is the most important organ involved in the biotransformation of drugs and hence also a prime site for drug-induced liver injury (DILI). Among the hepatotoxic drugs, paracetamol which is commonly used is a major offender, leading to about 40% of DILI. N-acetyl cysteine is commonly used to manage paracetamol poisoning. However, it has its own disadvantages. This study has been designed to probe into the possibility of an alternative drug for paracetamol-induced hepatotoxicity. The objective is to study the hepatoprotective effect of melatonin on paracetamol-induced hepatotoxicity in albino rats.
Materials and Methods: After prior approval from the IAEC, 36 albino rats were divided into six groups of six each. Each group received distilled water, paracetamol, paracetamol+N-acetyl cysteine, paracetamol+melatonin, and paracetamol+melatonin+N-acetyl cysteine, respectively. The liver function tests and histopathology of the liver of all the groups were compared. One-way ANOVA and post hoc Dunnett’s test were used.
Results: Melatonin alone and in combination with N-acetyl cysteine is found to have significant hepatoprotective effect in paracetamol-induced acute liver injury.
Conclusion: The main reason for hepatotoxicity is depletion of glutathione which is essential for conjugating the toxic metabolite N acetyl-p- benzoquinonimine (NAPQI) and CYP2E1 is playing the vital role of being the rate limiting enzyme initiating the cascade of events leading to acetaminophen hepatotoxicity. This is postulated to be reversed by melatonin.
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