Effect of fumonisin B-1 on rat hepatic P450 system
Department of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Utrecht, P.O. Box 80152, 3508 TD, Utrecht, The Netherlands
Environmental toxicology and pharmacology
04/2000; 8(3):197-204. DOI: 10.1016/S1382-6689(00)00040-5
The effects of the mycotoxin fumonisin B(1) (FB(1)) on the hepatic cytochrome P450 system were investigated in male rats dosed daily by oral gavage with 3 mg FB(1) per kg body weight for 9 consecutive days. FB(1) treatment resulted in a reduced weight gain. At the same time, CYP2E activity was increased, which is considered to mark the metabolic changes inherent to growth retardation in young rats. Treatment with FB(1) also resulted in a selective inhibition of CYP2C11 and to a lesser extent, CYP1A2 in liver microsomes obtained from treated animals, whereas it did not affect significantly the activity of CYP2A1/2A2, CYP2B1/2B2, CYP3A1/3A2 and CYP4A. The significant inhibition of CYP2C11 is considered to reflect a suppressed activity of protein kinase activity resulting from the inhibition of sphingolipid biosynthesis caused by FB(1).
Available from: Fatemeh Ahangarkani
- "These proteins are vital for maintaining the membrane structure, cells communications , cells interactions, cell morphology, extracellular interactions (such as cell-matrix and cell–cell adhesion) and cell differentiation, adjusting of growth factors, carcinogenicity and apoptosis. Also, sphingolipids act as the secondary messenger in signal transduction pathways (Galvanoa et al., 2002; Kpodoa et al., 2000; Spotti et al., 2000; Turner et al., 1999; Voss et al., 2007; Warfield & Gilchrist, 1999). 96 F. Ahangarkani et al. "
Available from: Maria Luisa Fernández-Cruz
- "In the literature, there are only a few conflicting reports that have studied the effects of FB1 on Cyp activity (Martínez-Larrañaga et al., 1996; Spotti et al., 2000). Of these, our results are similar to those obtained by Martínez-Larrañaga et al. (1996), who reported an increase of Cyp1A activity in the liver of Wistar rats exposed to FB1. "
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ABSTRACT: Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are mycotoxins widely found as cereal contaminants and their co-occurrence in corn has been associated with a high incidence of liver cancer. Both toxins are immunotoxic, with AFB1 being a procarcinogen, and its bioactivation through specific cytochrome P450 (Cyp) enzymes, such as Cyp1A, being a requirement for hepatocarcinogenic and toxic activities. This study evaluated the effects of these mycotoxins, alone or combined, on activation and expression of Cyp1A and its transcription factor aryl hydrocarbon receptor (Ahr) in hepatoma cell line H4IIE and spleen mononuclear cells of rats. The results demonstrate that in H4IIE cells, AFB1 induced an increase in Cyp1A activity and cyp1A transcription, associated with an enhanced Ahr activity, which suggests that this toxin can act as an Ahr agonist. Moreover, FB1 caused a small rise in Cyp1A activity and cyp1A expression. Similarly in spleen cells, AFB1 and FB1 induced overexpression of cyp1A and ahr genes. This work shows that the response potency was significantly higher for the mixture, indicating the existence of an interaction between both toxins. This study proposes the Ahr pathway activation as a toxicity mechanism of AFB1 and FB1, and highlights that FB1 may increase AFB1 bioactivation.
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Available from: Stefan Abel
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ABSTRACT: Alterations in the membrane structure and function of hepatocyte membranes by fumonisin B1 (FB1) have been proposed to play an important role in the disruption of growth regulatory effects and hence in the cancer-promoting
ability of the mycotoxin. Detailed analyses of lipids in liver microsomal fractions of rats exposed to different dietary levels
of FB1 over a period of 21 d indicated an increase in PC, PE, PI, and cholesterol (Chol). These changes decreased the PC/PE and
increased the total phospholipid/Chol ratios. When considering FA content, the quantities of total FA increased (P
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