fumonisin-b2 and Body-Weight

Aflatoxins (AF) and fumonisins (FU) are a major problem faced by poultry farmers, leading to huge economic losses. This experiment was conducted to determine the effects of AF (1 mg/kg of feed) and FU (25 mg/kg of feed), singly or in combination, on the lipid metabolism in commercial layers and investigate the efficacy of a commercial binder (2 kg/t of feed) on reducing the toxic effects of these mycotoxins. A total of 168 Hisex Brown layer hens, 37 wk of age, were randomized into a 3 × 2 + 1 factorial arrangement (3 diets with no binder containing AF, FU, and AF+FU; 3 diets with binder containing AF, FU, and AF+FU; and a control diet with no mycotoxins and binders), totaling 7 treatments. The hens contaminated with AF showed the characteristic effects of aflatoxicosis, such as a yellow liver, resulting from the accumulation of liver fat, lower values of plasma very low-density lipoprotein and triglycerides, and higher relative weight of the kidneys and liver. Hepatotoxic and nephrotoxic effects of FU were not observed in this study. On the other hand, the FU caused a reduction in small intestine length and an increase in abdominal fat deposition. The glucan-based binder prevented some of the deleterious effects of these mycotoxins, particularly the effects of AF on hepatic lipid metabolism, kidney relative weight, and FU in the small intestine.

Topics: Aflatoxin B1; Aflatoxins; Animal Feed; Animals; Body Weight; Chickens; Diet; Eating; Female; Food Contamination; Fumonisins; Glucans; Lipid Metabolism; Oviposition

Fumonisinmycotoxins are produced by Fusaria fungi that grow worldwide primarily on corn. Fumonisin B(1), the most predominant form in corn samples, is a renal carcinogen in male F344/N rats and a hepatocarcinogen in female B6C3F(1) mice when fed at concentrations higher than 50 ppm (70 micromol/kg) in the diet for 2 years. We sought to determine the relative toxicities of several naturally occurring fumonisin derivatives when included in the diet of female B6C3F(1) mice. Mice were fed diets containing fumonisin B(1), fumonisin B(2), fumonisin B(3), fumonisin P1, hydrolyzed-fumonisin B(1), N-(acetyl)fumonisin B(1), or N-(carboxymethyl)fumonisin B(1) (approximately 0, 14, 70, and 140 micromol/kg diet) for 28 days. None of the doses used caused a decrease in body weight gain over the 28 days. Serum levels of total bile acids, cholesterol, and alkaline phosphatase were increased only in mice receiving 72 and 143 micromol/kg fumonisin B(1), suggesting that only fumonisin B(1) was hepatotoxic in the mice. Corroborating this observation, the liver weight, relative to body weight, was decreased only in the mice that consumed 143 micromol/kg fumonisin B(1). Consistent with fumonisin B(1) inhibition of ceramide synthase, the liver sphinganine-to-sphingosine ratio was increased and the liver ceramide levels were decreased only in the mice receiving 72 and 143 micromol/kg fumonisin B(1). Increased hepatocellular apoptosis, hepatocellular hypertrophy, Kupffer cell hyperplasia, and macrophage pigmentation were detected in the mice consuming 72 and 143 micromol/kg fumonisin B(1). The other fumonisin derivatives did not alter serum analytes, organ weights, or hepatic structure. These results suggest that, of the naturally occurring fumonisins, fumonisin B(1) is the principal hepatotoxic derivative in the B6C3F(1) mouse.

Topics: Alkaline Phosphatase; Animals; Bile Acids and Salts; Blood Chemical Analysis; Body Weight; Carcinogens, Environmental; Ceramides; Cholesterol; Chromatography, High Pressure Liquid; Diet; Female; Fumonisins; Mice; Mice, Inbred Strains; Organ Size; Proteinuria; Sphingosine

Fumonisins B1 and B2 (FB1 and FB2) are fungal secondary metabolites produced by members of the genus Fusarium. Although FB1 is usually detected in greater quantities, FB2 frequently co-occurs in contaminated feeds and foods and contributes to the total toxin load. In the present study, the comparative toxicity of FB1 and FB2 was examined in male Sprague-Dawley rats administered toxin (0.75 mg/kg body weight) or vehicle control intraperitoneally (ip) for 2, 4 or 6 consecutive days. Clinical changes, including elevated serum cholesterol, alanine aminotransferase (ALT), creatinine and protein, were slightly more pronounced in FB1-treated rats. The most consistent hematological change was an increase in vacuolated bone marrow cells, which was more pronounced in FB1-treated rats. Histopathological changes were similar in FB1- and FB2-treated rats and included single cell necrosis in kidneys and liver, cytoplasmic vacuolation in adrenal cortex and lymphocytolysis in thymus. In the liver mRNA expression for the cyclin kinase inhibitor p21 gene was significantly increased in FB1- and FB2-treated rats, compared to controls. Expression of mRNA for the cyclin D1 gene was significantly depressed in FB2-treated rats. Hepatic cyclin E mRNA was elevated in response to FB1 and FB2 compared to controls. In FB2-treated animals this corresponded with decreased liver p27 mRNA expression. Hepatic proliferating cell nuclear antigen (PCNA) transcription was elevated in FB1- but not FB2- treated rats. Changes in liver microsomal protein levels of p27, cyclin E and PCNA were similar to changes in gene expression. In contrast, cyclin D1 protein levels were elevated in rats treated with FB1 and, to a lesser extent, FB2. The data indicate that FB1 and FB2 can alter the expression of genes associated with the cell cycle, and indicate a need for a further understanding of the mechanistic basis of FB1 and FB2 toxicity.

Topics: Animals; Body Weight; Carboxylic Acids; Cell Cycle; Cell Cycle Proteins; Eating; Fumonisins; Injections, Intraperitoneal; Kidney; Liver; Male; Mycotoxins; Organ Size; Rats; Rats, Sprague-Dawley; RNA, Messenger

Fumonisins are mycotoxins produced by Fusarium moniliforme, F. proliferatum and other Fusarium species, which are commonly found on corn, cause a variety of species-specific toxicoses, and have been linked to human oesophageal cancer in areas of southern Africa and China where corn is a dietary staple. The effect of nixtamalization, the process by which masa flour is produced by alkaline hydrolysis of corn, on the organ-specific toxicity of F. moniliforme culture material containing fumonisin B1 (FB1) was studied and the effectiveness of nixtamalization and water extraction for detoxifying culture material was compared. Male rats (n = 10/group) were fed diets containing 5% culture material equivalent weights of nixtamalized culture material (NX diet) providing 58 ppm hydrolysed FB1 but no FB1, water-extracted culture material (WE diet) providing 8 ppm FB1, or untreated culture material (CM diet) providing 71 ppm FB1 for 4 wk. An additional control group was fed a diet containing sound seed corn. Serum chemical and histopathological findings confirmed that the nixtamalized culture material was hepatotoxic and nephrotoxic. Hepatopathy was found in all rats fed the NX or CM diets. The lesions were qualitatively similar in these two groups, but were noticeably less severe in rats fed the NX diet. In contrast, only one rat fed the WE diet exhibited mild hepatopathy. Mild-to-moderate nephropathy resembling that induced by FB1 was found in all rats fed the NX, WE or CM diet. Thus, the organ-specific effects of nixtamalized culture material, containing no detectable FB1, were similar to those of the FB1-containing diet prepared from untreated culture material. Furthermore, nixtamalization was not as effective as water extraction as a detoxification method.

Topics: Adrenal Glands; Animals; Blood Urea Nitrogen; Body Weight; Carcinogens, Environmental; Creatinine; Eating; Flour; Fumonisins; Fusarium; Kidney; Liver; Male; Mycotoxins; Organ Size; Rats; Rats, Sprague-Dawley; Water; Zea mays

White Leghorn Cornell K-strain chicks (3 replicates of 16 per pen) were started at Day 7 on feed amended with Fusarium proliferatum culture material containing fumonisin B1, fumonisin B2, and moniliformin at 61, 10.5, and 42.7 ppm, respectively. Observed effects on performance of treated birds included reduced feed conversion at 2 wk, and reduced body weight of males and females up to 6 wk (P < or = .05). Splenic, thymic, and liver weights, normalized for body weight, were reduced (P < or = .05) with no change in bursa of Fabricius. No significant changes were observed histologically in the spleen, bursa, kidney, heart, liver, cecal tonsils, colon, or tibia. Significant suppression in total Ig and IgG levels occurred. Macrophages from treated chicks exhibited a 34% reduction in phagocytic activity. Natural killer cell activity was not affected. These findings, which showed that Fusarium toxins alter performance and immune end points in chickens, imply that chickens exposed to mycotoxins may be more susceptible to infectious diseases.

Topics: Animals; Antibody Formation; Body Weight; Chickens; Cyclobutanes; Female; Fumonisins; Fusarium; Immunity; Macrophages; Male; Mycotoxins; Organ Size; Sheep

Fusarium moniliforme (FM) is associated with equine leukoencephalomalacia (ELEM) and hepatotoxicities in horses and rats. The neurochemical effects of ELEM-associated corn naturally infected with FM and FM strain MRC 826 were studied in rats. Increases in brain 5-hydroxyindoleacetic acid (5-HIAA, major metabolite of serotonin, 5-HT) and 5-HIAA/5-HT ratios were observed in rats fed the ELEM-FM corn. These rats had reduced body weights (17%, P less than 0.01) and increased brain weight/body weight ratios (14%, P less than 0.01) as compared with controls that were fed commercial corn. Rats fed a rodent chow supplemented (16%, w/w) with corn cultures of FM (MRC 826) had brain 5-HT and 5-HIAA increased (11% and 60%, P less than 0.01, respectively). At 20% FM (MRC 826)-chow diet, the 5-HIAA levels were increased (18%, P less than 0.01). In both the 16% and 20% diets, brain 5-HIAA/5-HT ratios were increased (45%, P less than 0.01 and 10%, P less than 0.05), body weights reduced (30% and 18%, P less than 0.01) and brain weight/body weight ratios increased (40% and 16%, P less than 0.01), respectively. The incidences of microscopic liver lesions (particularly bile duct proliferations, hepatocellular hyperplasia, and focal necrosis) were consistent with rats fed the FM contaminated and FM-fortified diets. These results suggest a possible FM (ELEM-associated)-induced dysfunction in either 5-HT metabolism or 5-HIAA elimination in rat brains.

Topics: Animal Feed; Animals; Body Weight; Brain Chemistry; Encephalomalacia; Food Microbiology; Fumonisins; Fusarium; Horse Diseases; Horses; Male; Mycotoxins; Neurotransmitter Agents; Rats; Zea mays

Fusarium moniliforme has been associated with several diseases including equine leukoencephalomalacia, human esophageal cancer and hepatotoxicity/hepatocarcinogenicity in laboratory animals. The potential health risks to animals and humans posed by F. moniliforme contaminated grains cannot be assessed until the toxins are identified and toxicologically evaluated. As part of a systematic approach to identifying the hepatotoxins produced by F. moniliforme, diets containing aqueous and chloroform/methanol (1:1) extracts of F. moniliforme strain MRC 826 culture material (CM) and/or the extracted CM residues were fed to male Sprague-Dawley rats for four weeks. Serum alanine aminotransferase, aspartate amino-transferase and alkaline phosphatase activities were increased after two and four weeks and microscopic liver lesions were found in those animals fed aqueous CM extract and the CM residue after chloroform/methanol extraction. Fumonisins B1 and B2 were extracted from the CM by water, but not chloroform/methanol, and were present in the toxic diets at concentrations of 93-139 and 82-147 ppm, respectively. Nontoxic diets contained less than or equal to 22 ppm fumonisin B1 and less than or equal to 65 ppm fumonisin B2.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Body Weight; Carcinogens, Environmental; Chloroform; Eating; Fumonisins; Fusarium; Liver; Male; Methanol; Mycotoxins; Random Allocation; Rats; Rats, Inbred Strains; Water

Cultures on corn of Fusarium moniliforme MRC 826 are known to cause leukoencephalomalacia in horses and to be toxic and hepatocarcinogenic in rats. Culture material of this F. moniliforme isolate has also been shown to exhibit cancer-promoting activity in a short-term cancer initiation-promotion bioassay with diethylnitrosamine-initiated rats and the induction of gamma-glutamyl-transpeptidase-positive (GGT+) foci as an endpoint after 4 weeks of promotion. This bioassay was used as a monitoring system to isolate cancer-promoting compounds from cultures of F. moniliforme MRC 826. Culture material was successively extracted with ethyl acetate and CH3OH-H2O (3:1). Most of the cancer-promoting activity was recovered in the CH3OH-H2O extract and remained in the aqueous phase following partitioning of this extract between CH3OH-H2O (1:3) and CHCl3. The CH3OH-H2O fraction was chromatographed on an Amberlite XAD-2 column, and the active fraction was eluted with CH3OH. This fraction was chromatographed on a silica gel column with CHCl3-CH3OH-CH3COOH (6:3:1) as eluent and further purified on a C18 reverse-phase column. Two pure compounds were isolated, and these have been chemically characterized and given the trivial names fumonisin B1 and B2. At least 2 g of the major compound fumonisin B1 was purified from 1 kg of culture material. Fumonisin B1 in the diet (0.1%) significantly (P less than 0.001) induced the formation of GGT+ foci in the livers of initiated as well as noninitiated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Body Weight; Carcinogens, Environmental; Chromatography; Diethylnitrosamine; Fumonisins; Fusarium; gamma-Glutamyltransferase; Liver Neoplasms, Experimental; Male; Mutagenicity Tests; Mycotoxins; Rats; Rats, Inbred Strains