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dc.contributor.authorBhandari, Neetesh
dc.date.accessioned2014-03-03T20:02:59Z
dc.date.available2014-03-03T20:02:59Z
dc.date.issued2001-12
dc.identifier.otherbhandari_neetesh_200112_phd
dc.identifier.urihttp://purl.galileo.usg.edu/uga_etd/bhandari_neetesh_200112_phd
dc.identifier.urihttp://hdl.handle.net/10724/20282
dc.description.abstractFumonisin B1 (FB1), a toxic metabolite of Fusarium verticillioides, is a carcinogen and causative agent of various animal diseases. Our previous studies indicated the involvement of tumor necrosis factor ??(TNF?) in FB1 toxicity. The effect of FB1 on TNF??and related cytokines with interplay of other downstream signaling molecules was investigated in following studies.|Time course of TNF??and interferon ??(IFN?) expression after single sc or po dose of 25 mg/kg FB1 was studied on male BALB/c mice. IFN??and TNF??induction in liver peaked at 4 and 8 h, respectively after po FB1 treatment. TNF??induction after po FB1 treatment, correlated with the increase in liver enzymes. TNF??expression in spleen was unaltered. FB1 treatment by po route showed greater toxicity as compared to sc route.|Cytokine expression in liver, kidney and spleen was investigated in male B6,129 mice after a multiple subacute dose of 2.25 mg/kg/day FB1, for five days and sampled after 24 h. FB1 treatment caused a localized induction of TNF?, IFN??and interleukin (IL)-12 p40 in liver, with no changes in kidney and spleen. Increased TNF??expression in liver was localized in Kupffer cells. FB1 toxicity selectively induced T helper 1 cytokines, suggesting a role of liver macrophages and natural killer (NK) cells/NK1+ T cells, in localized cytokine induction.|Male and female BALB/c mice were tested for any gender differences after subacute FB1 toxicity, using similar five-day repeated treatment model. Female mice were more sensitive to FB1 toxicity, showing greater increase in liver enzymes and apoptotic cells. Higher toxicity in females correlated with their higher increase in liver sphingoid bases after FB1 treatment, and higher basal levels of cytokines. Gene alterations in cytokine network and apoptosis signaling molecules were measured in mice after acute or subacute FB1 treatment. FB1 treatment caused induction of various pro- and anti-inflammatory cytokines in liver. TNF??signaling molecules were induced with no changes in Fas signaling pathway. Induction of IL-1 receptor antagonist and c-Myc oncogene could be responsible for the cancer promoting effects of FB1.
dc.publisheruga
dc.rightspublic
dc.subjectFumonisin
dc.subjectMice
dc.subjectTNF alpha
dc.subjectCytokines
dc.subjectLiver
dc.subjectToxicity
dc.subjectSignaling
dc.titleInvolvement of tumor necrosis factor alpha and other cytokines in mouse fumonisin b1 toxicity
dc.typeDissertation
dc.description.degreePhD
dc.description.departmentPhysiology and Pharmacology
dc.description.majorPharmacology
dc.description.advisorRaghubir P. Sharma
dc.description.committeeRaghubir P. Sharma
dc.description.committeeCham E. Dallas
dc.description.committeeRoyal A. McGraw
dc.description.committeeThomas F. Murray
dc.description.committeeRonald T. Riley


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