Histomorphometrical changes in intestine structure and innervation following experimental fumonisins intoxication in male Wistar rats.

Fumonisins are highly toxic metabolites produced by Fusarium proliferatum and Fusarium verticillioides. Little is known about the effects of a chronic low level of fumonisins on intestinal structure and innervation in monogastric animals, even though the intestine is the first organ exposed to fumonisins. The influence of the most prevalent strains of fumonisins, FB1 and FB2, on intestinal and liver morphology, the enteric nervous system and intestinal epithelial cell prolif- eration was investigated in an experimental rat model of fumonisin intoxication. Adolescent (5-weeks-old), male Wistar rats were randomly divided into a control group (C group) not treated with fumonisins or intoxicated with fumonisins (FB group). FB1 together with FB2 were daily administered intragastrically at a dose of 90 mg/kg body weight for 21 days. The damaging effect was assessed by determination of the activity of ALAT and AspAT. Samples from the small intes- tine and liver were taken and blood samples were collected to determine the activity of gamma- -glutamyl transferase (GGT) and amylase. The exposure to FBs resulted in histopathological degenerative alterations in hepatocytes, including mild vacuolar degeneration and ballooning. FB exposure was also toxic in the duodenum and jejunum, where significant changes in morphology, cell proliferation, collagen wall fibres and innervation were observed. Taken together, the results obtained strengthen the hypothesis that chronic exposure to FBs could induce intestinal damage, including damage to the enteric nervous system and may have consequences for general health.

Screening Congo Red and its analogues for their ability to prevent the formation of PrP-res in scrapie-infected cells.

Transmissible spongiform encephalopathies (TSEs) are incurable, fatal diseases. The dye Congo Red (CR) can cure cells infected with agents of the sheep TSE, scrapie, but is not used as a therapeutic or prophylactic agent in vivo, as its effects are small, possibly due to low blood-brain barrier permeability, and complicated by its intrinsic carcinogenicity. In this paper, the development is described of a structure-activity profile for CR by testing a series of analogues of this dye for their ability to inhibit the formation of the protease-resistant prion protein, PrP-res, a molecular marker for the infectious agent, in the scrapie-infected, SMB cell line. It was found that the central benzidine unit in CR, which gives the molecule potential carcinogenicity, can be replaced by other, less toxic moieties and that the sulphonate groups on the core molecule can be replaced by carboxylic acids, which should improve the brain permeability of these compounds. However, detailed dose-response curves were generated for several derivatives and they revealed that, while some compounds showed inhibition of PrP-res accumulation at high concentrations, at low concentrations they actually stimulated levels of PrP-res above control values.