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.

Possible Role of Phosphatidylcholine and Sphingomyelin on Fumonisin B1-mediated Toxicity

“…Most of the PC is reabsorbed through the intestine as LPA and is returned to the liver and other tissues after the reacylation. Administration of methionine was unable to prevent FB1-mediated liver toxicity in rats 180) , although methionine partly prevented an increase of sphingosine, but not sphinganine. Therefore, decreased recycling of PC, excreted in the intestine through the bile, is likely the main mechanism for the FB1-mediated deficiency of hepatic PC.…”

Fumonisins: oxidative stress-mediated toxicity and metabolism in vivo and in vitro

“…Both agents prevented an increase in free sphingosine but not sphinganine, and they could not improve the GSH level in liver following FB 1 treatment (subcutaneous injection of 2.25 mg/kg b.w.) (He et al 2006). …”

“…FB 1 showed hepatotoxicity in C57BL/6 N mice accompanied by decreased GSH in the liver following the subcutaneous injection of 2.25 mg FB 1 / kg b.w. once daily for 5 days (He et al 2006). Intravenous injection of the tail vein with FB 1 (1.55 mg/kg) markedly decreased GSH levels in the liver (20 % of the control) and spleen (26 % of the control) (Atroshi et al 1999).…”