Exogenous Ghrelin Could Not Ameliorate3,4-methylenedioxymethamphetamine-induced Acute LiverInjury in the Rat: Involved Mechanisms

Mdma (3,4-methylenedioxymethamphetamine, ecstasy) is often abused by youth as arecreational drug. mdma abuse is a growing problem in different parts of the world. an importantadverse consequence of the drug consumption is hepatotoxicity of different intensities. however,the underlying mechanism of this toxicity has not been completely understood. ghrelin is a guthormone with growth hormone stimulatory effect. it expresses in liver, albeit at a much lower levelthan in stomach, and exerts a hepatoprotective effect. in this study, we investigated hepatotoxicityeffect of mdma alone and its combination with ghrelin as a hepatoprotective agent. mdmaand mdma+ ghrelin could transiently increase serum alanine aminotransferase (alt) andaspartate aminotransferase (ast) followed by tissue necrosis. however, they could significantlydecrease liver tumor necrosis factor-a (tnf-±) in both treatment groups. unexpectedly, inmdma treated rats, bax, bcl-xl, bcl-2, fas, fas ligand (fas-l), caspase 8, cytochrome c, caspase3 gene expression, and dna fragmentation were nearly unchanged. in addition, apoptosis inmdma+ ghrelin group was significantly reduced when compared with mdma treated animals.in all, mdma could transiently increase serum transaminases and induce tissue necrosis andliver toxicity. ghrelin, however, could not stop liver enzyme rise and mdma hepatotoxicity.mdma hepatotoxicity seems to be mediated via tissue necrosis than apoptotic and inflammatorypathways. conceivably, ghrelin as an anti-inflammatory and anti-apoptotic agent may not protecthepatocytes against mdma liver toxicity.