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Protein
Rats fed a low protein diet (4% casein) and given 50 μg of an undefined aflatoxin preparation exhibited a significant degree of toxic liver lesions within 3 weeks, compared with rats fed a highprotein diet (20% casein). These results were confirmed with the observation that a high protein diet (16% casein) protected monkeys from aflatoxin liver injury in comparison with animals on a 1% casein diet (Cullen & Newberne, 1994).
Protein A of Staphylococcus aureus is a potent immunostimulant and anticancer agent and has no toxic effects, even after multiple inoculations (Ray et al., 1984). Protein A has demonstrated its ability to decrease toxicity of drugs like cyclophosphamide (Zaidi et al., 1990) and environmental toxicants like carbon tetrachloride (Singh et al., 1990). Raisuddin et al. (1994) observed that protein A provided protection to rats from AFB1-induced immunotoxicity. Various parameters showing suppression of cell-mediated immunity following AFB1 exposure were reverted back towards normality in protein A-treated animals. Zaky et al. (1998) found that protein A counteracted the effect of AFB1 on haematocrit, globulin and bilirubin in broilers. According to Raisuddin et al. (1994) the protective effect of protein A on AFB1 toxicity is caused by inhibition of the activity of liver cytochrome P450 mixed function oxidase system that activates AFB1 to form the active metabolite that binds to cell DNA and RNA.
Choline and Methionine
The effect of a choline-deficient/low-methionine diet on hepatic aflatoxin-DNA adduct burden in male Fisher rats dosed with a carcinogenic regimen of AFB1, was examined in a model by Schrager et al. (1990). After three weeks of ingestion of a choline-deficient/low-methionine diet or a control semi-purified diet (sufficient time for enzyme activity to be altered), the rats were administered a carcinogenic regimen of 25 μg [3H] AFB1 for five days/week over two weeks. Six choline-deficient and four control diet rats were killed two hours after each dose so liver DNA could be isolated. In addition, hepatic DNA was isolated from animals 1, 2, 3, and 11 days after the last [3H] AFB1 administration. High-performance liquid chromatography (HPLC) analysis of aflatoxin-DNA adducts was performed to confirm radiometric determinations of DNA binding levels. No significant quantitative differences in AFB1-DNA adduct formation were observed among the dietary groups after the first exposure to [3H]AFB1; however, total aflatoxin-DNA adduct levels in the choline-deficient animals were increased significantly during the multiple-dose schedule. When total aflatoxin-DNA adduct levels were integrated over the ten day dose period, a 41% increase in adduct burden was determined for the choline-deficient animals. This increase in DNA damage is consistent with the hypothesis that DNA damage is related to tumor outcome, but the biochemical basis for this effect is not known.
Antioxidants
According to Souza et al. (1999), the principal manifestations of AFB1-induced toxicity are lipid peroxidation and oxidative DNA damage, which could be mitigated by antioxidants. Verma & Nair (1999) found that aflatoxin treatment caused a significant dose-dependent increase in lipid peroxidation, which could be due to reductions in the activities of superoxide dismutase, glutathione peroxidase and catalase. The levels of glutathione, total ascorbic acid and reduced ascorbic acid also declined significantly. Shen et al. (1994) measured malonaldehyde concentrations in liver homogenate as well as in subcellular fractions. Malonaldehyde is one of the end products from the chain reactions of lipid peroxidation. They showed a significant, persistent and dose-dependent increase of malonaldehyde after AFB1 administration in mice, suggesting that AFB1 caused lipid peroxidation in the liver. In this study, liver cell damage caused by AFB1 was measured by the increase of serum alanine aminotransferase and serum aspartate aminotransferase activities.
In an in vivo study in rats Shi et al. (1994) demonstrated that selenium inhibits AFB1-DNA binding and adduct formation. Shen et al. (1994) showed that the pretreatment of rats with selenium and vitamin E significantly inhibited the increase of malonaldehyde in liver homogenate induced by AFB1. A concomitant decrease of serum alanine aminotransferase and serum aspartate aminotransferase activities was also observed. Shen et al. (1994) suggested that the vitamin E inhibits lipid peroxidation by breaking the chain reaction initiated by •OH. In a similar study Verma & Nair (1999) supplemented adult Swiss strain male albino mice with vitamin E prior to aflatoxin treatment and found that the change in glutathione, total ascorbic acid and reduced ascorbic acid were significantly less after exposure to aflatoxin. The effect was more pronounced in animals treated with a low dosage of aflatoxin (25 μg aflatoxin/animal/day) than in those receiving a high dose (50 μg aflatoxin/animal/day). These findings (and also those of Verma & Nair, 2001) suggest that vitamin E pre-treatment significantly inhibited aflatoxin-induced lipid peroxidation. The protective effect of vitamin E against lipid peroxidation is mainly due to increased non-enzymatic and enzymatic antioxidants.
CHAPTER 1
Introduction
CHAPTER 2
Literature Review
1. Mycotoxins
1.1 Environmental factors affecting mycotoxin formation
1.2 Mycotoxins and health
1.3 Ochratoxins
1.4 Fusarium toxins
1.5 Citrinin
1.6 Ergot alkaloids
1.7 Aflatoxins
1.8 Limits and regulations for mycotoxins
1.9 Prevention of mycotoxin production
1.10 Detoxification and modified feeding strategies
2. Aflatoxins
2.1 Absorption
2.2 Metabolism
2.3 Elimination
2.4 The effects of aflatoxins in animals
2.5 Clinical Signs of aflatoxicosis in chickens
2.6 Factors affecting AFB1 toxicity
3. Humic Acids
3.1 The structure of humic acids
3.2 The therapeutically value of humic acids
3.3 Adsorption of humic acids to various compounds
3.4 Toxicology studies with humic acids
3.5 The derivation of humic acids from coal
3.6 Oxihumate-K S35
CHAPTER 3
In Vitro Binding Of Oxihumate To Different Mycotoxins
Abstract
Introduction
Materials and Methods
Results
Discussion
CHAPTER 4
Efficacy Of Oxihumate As An Aflatoxin Binder In Vivo
Abstract
Introduction
Materials and Methods
Aflatoxin Production
Experiment 1: Different dietary inclusion levels of oxihumate
Experiment 2: Toxicity of oxihumate in broilers
Experiment 3: The effect of oxihumate on aflatoxicosis in broilers
Experiment 4: The effect of oxihumate, alone and in combination with elevated dietary levels of
antioxidants on aflatoxicosis
Statistical Analysis
Ethical Approval
Results
Aflatoxin Production
Experiment 1: Different dietary inclusion levels of oxihumate
Experiment 2: Toxicity of oxihumate in broilers
Experiment 3: The effect of oxihumate on aflatoxicosis in broilers
Experiment 4: The effect of oxihumate, alone or in combination with elevated dietary levels of antioxidants on aflatoxicosis
Discussion
CHAPTER 5
In vitro effect of oxihumate on mitogen-induced proliferation of aflatoxin-treated lymphocytes
Abstract
Introduction
Materials and Methods
Results
Discussion
CHAPTER 6
Critical review and recommendations
CHAPTER 7:
References
