A preliminary investigation on renal and hepatic toxicity in rats fed purified fumonisin B1

Abstract

Fumonisins are metabolites of Fusarium moniliforme and other Fusarium spp. Fumonisin B1 (FB1) was hepatocarcinogenic (50 ppm, > or = 90% purity) when fed to male rats; however, neither the effects of FB1 on females nor the relationship between dietary FB1 levels and toxicity in rats has been reported. Male and female rats (three per sex per group) were fed diets fortified with 0, 15, 50 or 150 ppm FB1 (> or = 99% purity) for 4 weeks. There were no differences in general appearance or behavior among groups and significant differences in weight gain or food consumption were not found. Histopathological examinations and serum chemical profiles, including significant increases in triglycerides, cholesterol, and alkaline phosphatase, confirmed that 150 ppm FB1 was hepatotoxic to both sexes. Cortical nephrosis was found in males fed > or = 15 ppm and females fed > or = 50 ppm FB1. Both hepatic and renal lesions were consistent with those found in rats consuming F. moniliforme-infected corn. Thus, highly purified FB1 is unequivocally capable of inducing the subchronic liver and kidney lesions attributed to F. moniliforme.

Fumonisin b1 carcinogenicity in a two-year feeding study using F344 rats and B6C3F1 mice.

“…In this study we were unable to detect any hyperplasia or tumors in the esophageal tissue of rats or mice treated for 2 years with FB 1 . Although transient increases in esophageal epithelium labeling index have been reported following gavage administration of FB 1 to rats (37), other reports have indicated a lack of effect of FB 1 consumption on rat esophageal epithelial tissue (22)(23)(24)(25)(26).…”

“…The doses of FB 1 for the rats were based on toxicities detected in 28-day and 90-day subchronic studies (24)(25)(26). The doses for the bioassay were 0, 5, 15, 50, and 100 ppm FB 1 for female F344 rats and 0, 5, 15, 50, and 150 ppm FB 1 for the male F344 rats.…”

An overview of rodent toxicities: liver and kidney effects of fumonisins and Fusarium moniliforme.

“…Increased serum creatinine, decreased CO 2 and, less often, increased urea nitrogen occur in FB 1 -treated rats (57,58,79). Increased activities of N-acetyl-β-glucosaminidase, GGT, and lactate dehydrogenase have been found in urine, giving further clinical evidence of tubular injury (65,75).…”

“…None of these have reproduced the in vivo effects of toxic F. moniliforme isolates (30,(52)(53)(54). Conversely, the link between F. moniliforme and fumonisin has been independently established by several research groups; that is, the in vivo toxicities of corn (involved in ELEM outbreaks) naturally contaminated with F. moniliforme (9,55), culture materials of (toxic) F. moniliforme isolates, polar culture material extracts, and purified FB 1 are qualitatively the same (5,32,45,(56)(57)(58)(59)(60)(61). FB 2 , fumonisin B 3 (FB 3 ), and probably also hydrolyzed FB 1 (HFB 1 ) exert the same in vivo effects (62)(63)(64).…”

“…Others have noted a transient increase in the 5-bromo-2´-deoxyuridine labeling index in esophageal epithelium 3 days following an iv injection of 1.25 mg/kg bw (82), which suggests that FB 1 may be mitogenic under some conditions. However, there is no evidence from subchronic (5,57,58,61) or chronic (32,73) feeding studies of purified FB 1 that the esophagus is a target organ. Furthermore, FB 1 (5 mg/kg bw/day for 5 weeks) had no effect on the number of esophageal papillomas produced in rats concurrently given the esophageal carcinogen N-methylbenzylnitrosamine (83).…”