aflatoxin-m1 has been researched along with Disease-Models--Animal* in 3 studies
1 trial(s) available for aflatoxin-m1 and Disease-Models--Animal
2 other study(ies) available for aflatoxin-m1 and Disease-Models--Animal
Article | Year |
---|---|
Metabolomic Analysis Reveals the Mechanisms of Hepatotoxicity Induced by Aflatoxin M1 and Ochratoxin A.
Aflatoxin M1 (AFM1) is the only toxin with the maximum residue limit in milk, and ochratoxin A (OTA) represents a common toxin in cereals foods. It is common to find the co-occurrence of these two toxins in the environment. However, the interactive effect of these toxins on hepatoxicity and underlying mechanisms is still unclear. The liver and serum metabolomics in mice exposed to individual AFM1 at 3.5 mg/kg b.w., OTA at 3.5 mg/kg b.w., and their combination for 35 days were conducted based on the UPLC-MS method in the present study. Subsequent metabolome on human hepatocellular liver carcinoma (Hep G2) cells was conducted to narrow down the key metabolites. The phenotypic results on liver weight and serum indicators, such as total bilirubin and glutamyltransferase, showed that the combined toxins had more serious adverse effects than an individual one, indicating that the combined AFM1 and OTA displayed synergistic effects on liver damage. Through the metabolic analysis in liver and serum, we found that (i) a synergistic effect was exerted in the combined toxins, because the number of differentially expressed metabolites on combination treatment was higher than the individual toxins, (ii) OTA played a dominant role in the hepatoxicity induced by the combination of AFM1, and OTA and (iii) lysophosphatidylcholines (LysoPCs), more especially, LysoPC (16:1), were identified as the metabolites most affected by AFM1 and OTA. These findings provided a new insight for identifying the potential biomarkers for the hepatoxicity of AFM1 and OTA. Topics: Aflatoxin M1; Animals; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Food Contamination; Humans; Male; Metabolomics; Mice; Ochratoxins | 2022 |
Effects of dimethyl diphenyl bicarboxylate on the metabolism and hepatotoxicity of aflatoxin B1 in rats.
To study the effect of antihepatitis drug, dimethyl diphenyl bicarboxylate (DDB) on the metabolism and hepatotoxicity of aflatoxin B1(AFB1) in rats.. Rats were given orally DDB 300 mg.kg-1.d-1 for 3 days and then injected intraperitioneally with AFB1 1.5 mg.kg-1. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were examined 16 hours after the injection of AFB1. The in vitro metabolism of AFB1 by DDB-pretreated rat liver microsome was investigated by HPLC assay.. DDB (300 mg.kg-1) pretreatment provided significant protection against AFB1 hepatotoxicity as evidenced by the decrease of AFB1-elevated serum marker enzymes in rats. Pretreatment with DDB was shown to slightly increase the level of AFM1, the less toxic metabolite. DDB significantly increased the liver cytochrome P450 content, P450 isozyme 2B1-mediated 7-pentoxyresorufin O-dealkylase (PROD) activity, cytosolic glutahione (GSH) level and GSH S-transferase (GST) activities. In addition, DDB slightly increased P450 isozymes, 3A-mediated erythromycin-demethylase and 1A-mediated 7-ethoxyresorufin O-deethylase (EROD) activities.. The results indicate that DDB protected rats against AFB1 hepatotoxicity by increasing the detoxifying metabolism of AFB1 in the liver. Topics: Aflatoxin B1; Aflatoxin M1; Alanine Transaminase; Animals; Aspartate Aminotransferases; Biotransformation; Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme System; Dioxoles; Disease Models, Animal; Male; Microsomes, Liver; Protective Agents; Rats | 2002 |