Tehran University of Medical Sciences Acta Medica Iranica 0044-6025 55 12 2018 01 16 736 743 EN Ravieh Golchoobian Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Fatemeh Nabavizadeh Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Mehrdad Roghani Neurophysiology Research Center, Shahed University, Tehran, Iran. Alireza Foroumadi Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. AND Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran. Maryam Mohammadian Department of Physiology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. 2017 05 03 2017 07 22 Hepatotoxicity is one of the clinically adverse effects of ecstasy (3, 4-methylenedioxymethamphetamine; MDMA) consumption. The detoxification tissue, liver, plays a central role in maintaining circulating levels of glucose and lipid. Hypoglycemia and hypotriglyceridemia have been reported due to ecstasy abuse. Ghrelin is a 28-amino-acid peptide secreted predominantly from the stomach. It has been demonstrated that ghrelin has hepatoprotective effects and is able to increase blood glucose concentration. In the current study, we explored the effect of hepatotoxic dose of MDMA and therapeutic use of exogenous ghrelin on the serum levels of glucose and lipids in four groups of rats. MDMA caused a severe and transient reduction in circulating levels of glucose and triglyceride and increased serum LDL. However, cholesterol and HDL levels remained unchanged. Meanwhile, altered hepatic architecture was observed with intracellular vacuolation that may indicate intracellular accumulation of lipid droplets. In addition, following ghrelin administration, the blood sugar levels improved and LDL levels returned to the baseline value, and ghrelin treatment did not improve triglycerides levels. These results showed that MDMA causes hypoglycemia, hypotriglyceridemia, and hyper LDL-cholesterolemia. To our knowledge, this is the first report showing ghrelin administration could improve hypoglycemia and normalize LDL levels induced by MDMA and partially restore hepatic architecture. https://acta.tums.ac.ir/index.php/acta/article/view/6420 https://acta.tums.ac.ir/index.php/acta/article/download/6420/5025