Tolerance to fumonisin toxicity in a mouse strain lacking the P75 tumor necrosis factor receptor

Sharma, Raghubir P.; Bhandari, Neetesh; Riley, Ronald T.; Voss, Kenneth A.; Meredith, Filmore I.

doi:10.1016/s0300-483x(99)00168-7

Cited by 50 publications

(26 citation statements)

References 36 publications

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“…Disruption of sphingolipid metabolism and hepatotoxicity in mice exposed to fumonisins has been repeatedly correlated (Sharma et al, 1997(Sharma et al, , 2000a(Sharma et al, ,b, 2002. While TNF␣ affects sphingolipid metabolism by increasing cell ceramide through activation of sphingomyelinase, the role of TNF␣ in fumonisin-induced hepatic injury is unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Evaluations were done without knowledge of the animals' strain or treatment. The specimens were first evaluated to determine the presence of lesions that were consistent with those induced by fumonisins in mice (National Toxicology Program, 2001;Sharma et al, 1997Sharma et al, , 2000a. Accordingly, apoptosis, mitotic figures, hepatic anisocytosis, anisonucleosis, cytomegaly and cytoplasmic eosinophilia were considered evidence of fumonisin exposure.…”

Section: Evaluation Of Hepatotoxicitymentioning

confidence: 99%

“…Mice lacking a functional TNF receptor 1 (p55) or TNF receptor 2 (p75) were protected against the hepatotoxic effects of FB 1 when the mycotoxin was given subcutaneously for 5 consecutive days (Sharma et al, 2000a. Mice that over-expressed the human TNF␣ transgene also exhibited less severe hepatotoxicity than wildtype mice (Sharma et al, 2000b), whereas TNF␣-null mice given FB 1 using the same dosing scheme exhibited increased apoptosis and cell proliferation compared to wild-type mice (Sharma et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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The role of tumor necrosis factor α and the peroxisome proliferator-activated receptor α in modulating the effects of fumonisin in mouse liver

et al. 2006

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Section: Discussionmentioning

confidence: 99%

Section: Evaluation Of Hepatotoxicitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The role of tumor necrosis factor α and the peroxisome proliferator-activated receptor α in modulating the effects of fumonisin in mouse liver

et al. 2006

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“…In mice dosed once subcutaneously with FB 1 , the free sphinganine concentration in liver and kidney was significantly increased within 2 hr of dosing and in liver returned to the control concentration after 24 hr (50). (14)(15)(16)(17). The correlation between free sphinganine (nanomoles per gram fresh weight) in liver and (A) histopathologic findings (liver scores from hematoxylin-and eosin-stained sections) in livers, and (B) liver enzymes (ALT= alanine aminotransferase, units/liter) in serum from six (3-4 of each) different types of male mice dosed subcutaneously with 2.25 mg FB 1 /kg body weight/day for 5 days.…”

Section: Increased Free Sphingoid Basesmentioning

confidence: 99%

“…The free sphinganine was analyzed as described in Riley et al (83) and TBARS as per Abel and Gelderblom (33). Additional details of the dosing regimen, criteria for liver scores, and rationale for selecting mouse strains have been described elsewhere (14)(15)(16)(17). Care and treatment of animals were approved by the University of Georgia Animal Use Committee.…”

Section: Increased Free Sphingoid Basesmentioning

confidence: 99%

Sphingolipid perturbations as mechanisms for fumonisin carcinogenesis.

Riley

Enongene

Voss

et al. 2001

Environ Health Perspect

179

100

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There is a great deal of evidence that altered sphingolipid metabolism is associated with fumonisin-induced animal diseases including increased apoptotic and oncotic necrosis, and carcinogenesis in rodent liver and kidney. The biochemical consequences of fumonisin disruption of sphingolipid metabolism most likely to alter cell regulation are increased free sphingoid bases and their 1-phosphates, alterations in complex sphingolipids, and decreased ceramide (CER) biosynthesis. Because free sphingoid bases and CER can induce cell death, the fumonisin inhibition of CER synthase can inhibit cell death induced by CER but promote free sphingoid base-induced cell death. Theoretically, at any time the balance between the intracellular concentration of effectors that protect cells from apoptosis (decreased CER, increased sphingosine 1-phosphate) and those that induce apoptosis (increased CER, free sphingoid bases, altered fatty acids) will determine the cellular response. Because the balance between the rates of apoptosis and proliferation is important in tumorigenesis, cells sensitive to the proliferative effect of decreased CER and increased sphingosine 1-phosphate may be selected to survive and proliferate when free sphingoid base concentration is not growth inhibitory. Conversely, when the increase in free sphingoid bases exceeds a cell's ability to convert sphinganine/sphingosine to dihydroceramide/CER or their sphingoid base 1-phosphate, then free sphingoid bases will accumulate. In this case cells that are sensitive to sphingoid base-induced growth arrest will die and insensitive cells will survive. If the cells selected to die are normal phenotypes and the cells selected to survive are abnormal, then cancer risk will increase.

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S-adenosylmethionine or 5′-methylthioadenosine are unable to prevent fumonisin B1 hepatotoxicity in mice despite increased oxidation in liver

Suzuki

Sharma

2006

J. Appl. Toxicol.

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Fumonisins are mycotoxins produced by the fugus Fusarium verticillioides, a common fungus growing on corn. Fumonisin B(1) (FB(1)) is the most toxic and prevalent fumonisin detected in corn and corn-based foods. It produces species-, gender-specific damage, and is hepatotoxic and nephrotoxic in rodents. Disruption of sphingolipid metabolism resulting from inhibition of ceramide synthase leads to alterations of cell signaling events, particularly tumor necrosis factor (TNF)alpha signal pathways and to the toxic effects of FB(1). It has been reported that FB(1) toxicity involves oxidative stress. S-adenosylmethionine (SAM) and methylthioadenosine (MTA), an intermediate metabolite in SAM metabolism, are hepatoprotective by modulating TNFalpha expression and increasing reduced glutathione (GSH) levels. The current study investigated the effects of SAM and MTA on FB(1) hepatotoxicity in C57BL/6N mice. The animals were given SAM or MTA by intraperitoneal injection of 25 mg kg(-1) body weight every 12 h when they received subcutaneous injection of 2.25 mg FB(1) kg(-1) body weight once daily for 5 days. The results showed that neither SAM nor MTA protected FB(1)-induced liver damage indicated by the increases in activities of plasma alanine aminotransferase and aspartate aminotransferase as well as the number of apoptotic hepatocytes. Both agents prevented an increase of free sphingosine but not sphinganine. Neither SAM nor MTA modified the FB(1)-induced expression of TNFalpha, interleukin (IL)-1alpha or IL-1 receptor antagonist. The decreased GSH in liver following FB(1) treatment was not protected by either agent. The data indicate that SAM and MTA are ineffective in protecting against FB(1) toxic effects.

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Tolerance to fumonisin toxicity in a mouse strain lacking the P75 tumor necrosis factor receptor

Cited by 50 publications

References 36 publications

The role of tumor necrosis factor α and the peroxisome proliferator-activated receptor α in modulating the effects of fumonisin in mouse liver

The role of tumor necrosis factor α and the peroxisome proliferator-activated receptor α in modulating the effects of fumonisin in mouse liver

Sphingolipid perturbations as mechanisms for fumonisin carcinogenesis.

S-adenosylmethionine or 5′-methylthioadenosine are unable to prevent fumonisin B1 hepatotoxicity in mice despite increased oxidation in liver

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