Effect of melatonin and n-acetylcysteine on hepatic injury in rat induced by methanol intoxication: a comparative study

M. Koksal 1, Z. Kurcer 2, D. Erdogan 3, M. Iraz 4, M. Tas 5, M.A. Eren 6, T. Aydogan 6, T. Ulas 6

¹ Department of Histology and Embryology, Faculty of Medicine, Harran University, Sanliurfa (Turkey)

² Department of Pharmacology, Faculty of Medicine, Zonguldak Karaelmas University, Zonguldak (Turkey)

³ Department of Histology and Embryology, Faculty of Medicine, Gazi University, Ankara (Turkey)

⁴ Department of Pharmacology, Faculty of Medicine, Bezmialem Vakif University, Istanbul (Turkey)

⁵ Andrology Unit, Kanuni Sultan Süleyman Research and Education Hospital, Istanbul (Turkey)

⁶ Department of Internal Medicine, Faculty of Medicine, Harran University, Sanliurfa (Turkey)

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• Pharmacology

Background: Methanol intoxication leads liver injury; in contrast melatonin and n-acetyl cysteine (NAC) are known to have protective effects on liver.

Aim: We aimed to investigate the ultrastructural effects of melatonin and NAC on livers of methanol intoxicated rats and compare potential protective effects of melatonin and NAC on their liver ultrastructure.

Materials and Methods: Fifty-six adult male Wistar rats were carried out and were randomized to eight groups that have seven rats each: Control groups (C 6h, C 24h), treated with intragastric (i.g.) 1.0 ml saline; Methanol groups (M 6h, M 24h), treated with a dose of 3 g/kg i.g. methanol; Melatonin plus methanol groups (MEL+M 6h, MEL+M 24h), treated with dose of 10 mg/kg i.p melatonin immediately, following with a dose of 3 g/kg i.g. methanol; NAC plus methanol groups (NAC+M 6h, NAC+M 24h), treated with dose of 150 mg/kg, following with a dose of 3 g/kg i.g. methanol. 24 h group rats were given the same dose of melatonin and NAC 12 h after intoxication. Electron microscopy was used to evaluate histological changes in liver tissue at both 6th and 24th hour.

Results: Histopathological damage was found to be higher in methanol-induced intoxicated rats compared with the controls. Extensive tubules of smooth endoplasmic reticulum, increased mitochondria, increased primary lysosomes and some marked openings of bile canaliculus were distinguished. Melatonin administration prevents liver injury especially in early hours and although not as effective as melatonin, NAC also prevents liver injury.

Conclusions: Melatonin is much more efficient than NAC, as well as significantly greater hepatoprotective effect against the liver injury secondary to the methanol intoxication.

Corresponding Author: Mete Köksal, MD; e-mail: mkoksal@harran.edu.tr

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