Abstract
Fumonisin B{sub 1} (FB{sub 1}) is a mycotoxin produced by Fusarium verticillioides, commonly present in corn and other cereals. Exposure to FB{sub 1} causes organ-specific diseases in various species, e.g., equine leukoencephalomalacia and porcine pulmonary edema; in mice the response is hepatotoxicity. We earlier reported that ceramide synthase inhibition by FB{sub 1}, the initial biochemical effect of this mycotoxin, results in modulation of cytokine network in response to accumulated free sphingoid bases. In the current study we used NZB/NZW-F1 (NZBW) mice that have modified cytokine expression and develop lupus beginning at 5 months of age. The NZBW and C57BL/6J (CBL) mice (appropriate control) were given five daily subcutaneous injections of either saline or 2.25 mg FB{sub 1}/kg/day and euthanized 24 h after the last treatment. Peripheral leukocyte counts were higher after exposure to FB{sub 1} in CBL but not in NZBW. FB{sub 1} treatment caused increases of plasma alanine aminotransferase and aspartate aminotransferase activity in CBL mice indicating hepatotoxicity; no elevation of circulating liver enzymes was recorded in NZBW mice. Hepatotoxic responses were confirmed by microscopic evaluation of apoptotic cells. The FB{sub 1}-induced proliferation of cells observed in CBL strain was abolished in NZBW animals. The sphinganine accumulation in liver
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Sharma, Raghubir P;
[1]
Quanren, He;
[1]
Riley, Ronald T
[2]
- Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389 (United States)
- Toxicology and Mycotoxin Research Unit, USDA-ARS, Athens, GA 30604 (United States)
Citation Formats
Sharma, Raghubir P, Quanren, He, and Riley, Ronald T.
Lupus-prone NZBWF1/J mice, defective in cytokine signaling, are resistant to fumonisin hepatotoxicity despite accumulation of liver sphinganine.
Ireland: N. p.,
2005.
Web.
doi:10.1016/j.tox.2005.07.024.
Sharma, Raghubir P, Quanren, He, & Riley, Ronald T.
Lupus-prone NZBWF1/J mice, defective in cytokine signaling, are resistant to fumonisin hepatotoxicity despite accumulation of liver sphinganine.
Ireland.
https://doi.org/10.1016/j.tox.2005.07.024
Sharma, Raghubir P, Quanren, He, and Riley, Ronald T.
2005.
"Lupus-prone NZBWF1/J mice, defective in cytokine signaling, are resistant to fumonisin hepatotoxicity despite accumulation of liver sphinganine."
Ireland.
https://doi.org/10.1016/j.tox.2005.07.024.
@misc{etde_20720467,
title = {Lupus-prone NZBWF1/J mice, defective in cytokine signaling, are resistant to fumonisin hepatotoxicity despite accumulation of liver sphinganine}
author = {Sharma, Raghubir P, Quanren, He, and Riley, Ronald T}
abstractNote = {Fumonisin B{sub 1} (FB{sub 1}) is a mycotoxin produced by Fusarium verticillioides, commonly present in corn and other cereals. Exposure to FB{sub 1} causes organ-specific diseases in various species, e.g., equine leukoencephalomalacia and porcine pulmonary edema; in mice the response is hepatotoxicity. We earlier reported that ceramide synthase inhibition by FB{sub 1}, the initial biochemical effect of this mycotoxin, results in modulation of cytokine network in response to accumulated free sphingoid bases. In the current study we used NZB/NZW-F1 (NZBW) mice that have modified cytokine expression and develop lupus beginning at 5 months of age. The NZBW and C57BL/6J (CBL) mice (appropriate control) were given five daily subcutaneous injections of either saline or 2.25 mg FB{sub 1}/kg/day and euthanized 24 h after the last treatment. Peripheral leukocyte counts were higher after exposure to FB{sub 1} in CBL but not in NZBW. FB{sub 1} treatment caused increases of plasma alanine aminotransferase and aspartate aminotransferase activity in CBL mice indicating hepatotoxicity; no elevation of circulating liver enzymes was recorded in NZBW mice. Hepatotoxic responses were confirmed by microscopic evaluation of apoptotic cells. The FB{sub 1}-induced proliferation of cells observed in CBL strain was abolished in NZBW animals. The sphinganine accumulation in liver after FB{sub 1} was equal in both strains of mice. The NZBW strain lacked the FB{sub 1}-induced increases in the expression of liver tumor necrosis factor {alpha}, interferon {gamma}, receptor interacting protein (RIP), and tumor necrosis factor {alpha}-related apoptosis-inducing ligand (TRAIL), observed in CBL. Results confirmed our hypothesis that initial altered sphingolipid metabolism caused by FB{sub 1} leads to perturbation of liver cytokine network and ultimate cellular injury; the mice deficient in cytokine signaling are refractory to FB{sub 1} hepatotoxicity.}
doi = {10.1016/j.tox.2005.07.024}
journal = []
issue = {1}
volume = {216}
place = {Ireland}
year = {2005}
month = {Dec}
}
title = {Lupus-prone NZBWF1/J mice, defective in cytokine signaling, are resistant to fumonisin hepatotoxicity despite accumulation of liver sphinganine}
author = {Sharma, Raghubir P, Quanren, He, and Riley, Ronald T}
abstractNote = {Fumonisin B{sub 1} (FB{sub 1}) is a mycotoxin produced by Fusarium verticillioides, commonly present in corn and other cereals. Exposure to FB{sub 1} causes organ-specific diseases in various species, e.g., equine leukoencephalomalacia and porcine pulmonary edema; in mice the response is hepatotoxicity. We earlier reported that ceramide synthase inhibition by FB{sub 1}, the initial biochemical effect of this mycotoxin, results in modulation of cytokine network in response to accumulated free sphingoid bases. In the current study we used NZB/NZW-F1 (NZBW) mice that have modified cytokine expression and develop lupus beginning at 5 months of age. The NZBW and C57BL/6J (CBL) mice (appropriate control) were given five daily subcutaneous injections of either saline or 2.25 mg FB{sub 1}/kg/day and euthanized 24 h after the last treatment. Peripheral leukocyte counts were higher after exposure to FB{sub 1} in CBL but not in NZBW. FB{sub 1} treatment caused increases of plasma alanine aminotransferase and aspartate aminotransferase activity in CBL mice indicating hepatotoxicity; no elevation of circulating liver enzymes was recorded in NZBW mice. Hepatotoxic responses were confirmed by microscopic evaluation of apoptotic cells. The FB{sub 1}-induced proliferation of cells observed in CBL strain was abolished in NZBW animals. The sphinganine accumulation in liver after FB{sub 1} was equal in both strains of mice. The NZBW strain lacked the FB{sub 1}-induced increases in the expression of liver tumor necrosis factor {alpha}, interferon {gamma}, receptor interacting protein (RIP), and tumor necrosis factor {alpha}-related apoptosis-inducing ligand (TRAIL), observed in CBL. Results confirmed our hypothesis that initial altered sphingolipid metabolism caused by FB{sub 1} leads to perturbation of liver cytokine network and ultimate cellular injury; the mice deficient in cytokine signaling are refractory to FB{sub 1} hepatotoxicity.}
doi = {10.1016/j.tox.2005.07.024}
journal = []
issue = {1}
volume = {216}
place = {Ireland}
year = {2005}
month = {Dec}
}