Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fumonisin B1 is a mycotoxin commonly found on corn. It is hepatotoxic and nephrotoxic in domestic and experimental animals, and causes equine leukoencephalomalacia and porcine pulmonary oedema. It is a potent inhibitor of ceramide synthase. Inhibition leads to accumulation of free sphingoid bases in cells and tissues. In pig kidney epithelial cells (LLC-PK1), fumonisin B1 induces increased tumour necrosis factor alpha (TNFalpha) expression independent of the accumulation of sphingoid bases. The objective of this study was to investigate pharmacological approaches for intervening in fumonisin B1 toxicity using the LLC-PK1 cell model. The toxicity of fumonisin B1 was assayed using cell viability and lactate dehydrogenase (lactate dehydrogenase) release. Pretreatment of cells with myriocin, preventing sphinganine accumulates, prevented the fumonisin B1-induced decrease in cell viability and increased lactate dehydrogenase release. Modulation of adenosine receptor activity did not reduce the fumonisin B1 cytotoxicity. As with myriocin, silymarin pretreatment prevented the fumonisin B1-induced effects on cell viability and lactate dehydrogenase release. When added 6 or 24 hr after treatment of cells with fumonisin B1, both myriocin and silymarin reversed the decreased cell viability and suppressed the increased lactate dehydrogenase release. Myriocin, but not silymarin, blocked the accumulation of sphinganine in fumonisin B1-treated cells. Silymarin, unlike myriocin, induced expression of TNFalpha to an extent similar to fumonisin B1, but pretreatment with silymarin decreased the fumonisin B1-induced TNFalpha expression in LLC-PK1 cells. Results suggest that the mechanisms by which myriocin and silymarin protect renal cells are different, and silymarin potentially prevents fumonisin B1-induced toxicity by modulating TNFalpha expression or signals downstream of the inhibition of ceramide synthase.
 ...
PMID:Pharmacological antagonism of fumonisin B1 cytotoxicity in porcine renal epithelial cells (LLC-PK1): a model for reducing fumonisin-induced nephrotoxicity in vivo. 1207 8

Fumonisin B(1) (FB(1)) is a mycotoxin produced by Fusarium verticillioides found on corn and corn-based foods. It causes equine leukoencephalomalacia, porcine pulmonary edema, and liver and kidney damage in most animal species. Fumonisin B(1) perturbs sphingolipid metabolism by inhibiting ceramide synthase activity, leading to the production of cell signaling factors including tumor necrosis factor alpha (TNF-alpha). The signal pathways of TNF-alpha are important factors in the pathogenesis of FB(1) hepatotoxicity. In the present study, female BALB/c mice were treated daily with 750 mg/kg silymarin by gavage and 2.25 mg/kg FB(1) subcutaneously for 3 days. Then, 1 day after the last FB(1) injection, the mice were euthanized and blood and tissues were sampled for analyses. Silymarin significantly diminished FB(1)-induced elevation of plasma alanine aminotransferase and aspartate aminotransferase activities and the number of apoptotic hepatocytes, while it augmented hepatocyte proliferation indicated by an increase in proliferating cells. Silymarin dramatically potentiated FB(1)-induced accumulation of free sphinganine and sphingosine in both liver and kidney. Silymarin itself slightly increased expression of hepatic TNF-alpha; however, it prevented the FB(1)-induced increases in TNF-alpha, TNF receptor 1, TNF receptor-associated apoptosis-inducing ligand, lymphotoxin beta, and interferon gamma. The induction of transforming growth factor beta1 expression in liver following FB(1) treatment was not affected by silymarin. These findings suggest that silymarin protected against FB(1) liver damage by inhibiting biological functions of free sphingoid bases and increasing cellular regeneration.
 ...
PMID:Silymarin protects against liver damage in BALB/c mice exposed to fumonisin B1 despite increasing accumulation of free sphingoid bases. 1510 51