Methapyrilene: Histamine Antagonists
Methapyrilene
Methapyrilene, a histamine antagonist belongs to the class of pyridine chemicals, was widely used in many non-prescription drugs until 1979, when it was demonstrated to cause the development of liver tumors in rats. Because of the absence of DNA adducts in the livers of rats treated with methapyrilene, the hepatocarcinogenicity of methapyrilene has been attributed to non-genotoxic mechanisms, mainly to induction of mitochondrial dysfunction and disruption of the cellular epigenome. Indeed, exposure to methapyrilene caused target organ-specific epigenetic alterations that consisted of a reduction in the levels of cytosine DNA methylation and demethylation and deacetylation of histone lysine residues, with the greatest decrease
Methapyrilene, a histamine antagonist belongs to the class of pyridine chemicals, was widely used in many non-prescription drugs until 1979, when it was demonstrated to cause the development of liver tumors in rats. Because of the absence of DNA adducts in the livers of rats treated with methapyrilene, the hepatocarcinogenicity of methapyrilene has been attributed to non-genotoxic mechanisms, mainly to induction of mitochondrial dysfunction and disruption of the cellular epigenome. Indeed, exposure to methapyrilene caused target organ-specific epigenetic alterations that consisted of a reduction in the levels of cytosine DNA methylation and demethylation and deacetylation of histone lysine residues, with the greatest decrease