|Enongene, E - CFSAN-FDA, WASHINGTON, DC|
|Burns, T - SC STATE UNIV., SC|
|Owen, J - UGA-INTERDIS TOX PROGRAM|
Submitted to: Toxicologist
Publication Type: Abstract Only
Publication Acceptance Date: January 15, 2001
Publication Date: March 1, 2001
Interpretive Summary: No Interpretive Summary Required. Abstract presented at the 40th Annual Meeting of the Society of Toxicology, San Francisco, California, March 25-29, 2001.
Technical Abstract: Fumonisins are produced by F. moniliforme, fungi found in corn. They are found in corn-based foods and have been implicated as human carcinogens. Fumonisins are liver and kidney toxins and fumonisin B1 is carcinogenic to male rats (kidney or liver) and female mice (liver). Male rats are, for undetermined reasons, more sensitive to fumonisin-induced nephrotoxicity than females. Recently, fumonisins have been identified as cardiotoxins in swine, but the heart has not been considered a target organ in rats. Castrated (at weaning) and intact young male Sprague-Dawley rats were fed diets containing 0, 2.3, or 14% F. moniliforme culture material (CM), providing 0, 65 or 380 ppm fumonisins, respectively, for 4, 7, or 14 days. Dose-dependent decreases in kidney/brain weight ratios and significant microscopic lesions typical of those caused by fumonisins were found at 4, 7, and 14 days (n=5 rats/group/time period). The time course and intensity of the response were similar in castrated and intact animals. These findings indicate that fumonisin-induced nephrotoxicity in male rats is not testosterone dependent. Microscopic heart lesions were not found but heart/brain weight ratios were decreased on days 4 through 14 in rats fed the 14% CM diet. Furthermore, cardiac sphinganine (a substrate for the enzyme ceramide synthase) concentrations were significantly increased at days 7 and 14 in rats fed the 14% CM diet. The later finding is consistent with the well established role of fumonisins as ceramide synthase inhibitors, therefore providing additional evidence that the heart is a target organ of fumonisins in rats.