title: S-adenosylmethionine or 5'-methylthioadenosine are unable to prevent fumonisin B1 hepatotoxicity in mice despite increased oxidation in liver.
abstract: Fumonisins are mycotoxins produced by the fugus Fusarium verticillioides, a common fungus growing on corn. Fumonisin B(1) (FB(1)) is the most toxic and prevalent fumonisin detected in corn and corn-based foods. It produces species-, gender-specific damage, and is hepatotoxic and nephrotoxic in rodents. Disruption of sphingolipid metabolism resulting from inhibition of ceramide synthase leads to alterations of cell signaling events, particularly tumor necrosis factor (TNF)alpha signal pathways and to the toxic effects of FB(1). It has been reported that FB(1) toxicity involves oxidative stress. S-adenosylmethionine (SAM) and methylthioadenosine (MTA), an intermediate metabolite in SAM metabolism, are hepatoprotective by modulating TNFalpha expression and increasing reduced glutathione (GSH) levels. The current study investigated the effects of SAM and MTA on FB(1) hepatotoxicity in C57BL/6N mice. The animals were given SAM or MTA by intraperitoneal injection of 25 mg kg(-1) body weight every 12 h when they received subcutaneous injection of 2.25 mg FB(1) kg(-1) body weight once daily for 5 days. The results showed that neither SAM nor MTA protected FB(1)-induced liver damage indicated by the increases in activities of plasma alanine aminotransferase and aspartate aminotransferase as well as the number of apoptotic hepatocytes. Both agents prevented an increase of free sphingosine but not sphinganine. Neither SAM nor MTA modified the FB(1)-induced expression of TNFalpha, interleukin (IL)-1alpha or IL-1 receptor antagonist. The decreased GSH in liver following FB(1) treatment was not protected by either agent. The data indicate that SAM and MTA are ineffective in protecting against FB(1) toxic effects.
authors.affiliation: Department of Physiology and Pharmacology, The University of Georgia, Athens, GA 30602, USA. qhe@cydexinc.com
authors.forename: Quanren
authors.initials: Q
authors.lastname: He
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Raghubir P
authors.initials: RP
authors.lastname: Sharma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003839:Deoxyadenosines / Q000494:pharmacology*; D037341:Fumonisins / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D013110:Sphingosine / Q000032:analysis; D013872:Thionucleosides / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D003839:Deoxyadenosines; D037341:Fumonisins; D013872:Thionucleosides; C056933:fumonisin B1; C008500:5'-methylthioadenosine; D012436:S-Adenosylmethionine; D005978:Glutathione; D013110:Sphingosine