Induction of apoptotic lesions in liver and lymphoid tissues and modulation of cytokine mRNA expression by acute exposure to deoxynivalenol in piglets.
Six 1-month-old piglets were intravenously injected with deoxynivalenol (DON) at the concentration of 1 mg/kg body weight, with three pigs each necropsied at 6 and 24 h post-injection (PI) for investigation of hepatotoxicity and immunotoxicity with special attention to apoptotic changes and cytokine mRNA expression. Histopathological examination of the DON-injected pigs revealed systemic apoptosis of lymphocytes in lymphoid tissues and hepatocytes. Apoptosis of lymphocytes and hepatocytes was confirmed by the TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method and immunohistochemical staining against singlestranded DNA and cleaved caspase-3. The number of TUNELpositive cells in the thymus and Peyer's patches of the ileum was increased at 24 h PI compared to 6 h PI, but the peak was at 6 h PI in the liver. The mRNA expression of interleukin (IL)-1beta, IL-6, IL-18, and tumor necrosis factor (TNF)-alpha in the spleen, thymus and mesenteric lymph nodes were determined by semi-quantitative RT-PCR, and elevated expression of IL-1beta mRNA at 6 h PI and a decrease of IL-18 mRNA at 24 h PI were observed in the spleen. IL-1beta and IL-6 mRNA expressions increased significantly at 6 h PI in the thymus, but TNF-alpha decreased at 6 h PI in the mesenteric lymph nodes. These results show the apoptosis of hepatocytes suggesting the hepatotoxic potential of DON, in addition to an immunotoxic effect on the modulation of proinflammatory cytokine genes in lymphoid organs with extensive apoptosis of lymphocytes induced by acute exposure to DON in pigs.
Mikami
Osamu
O
Safety Research Team, National Institute of Animal Health, Tsukuba, 305-0856, Japan. mikami@affrc.go.jp
Yamaguchi
Hiroyuki
H
Murata
Hideo
H
Nakajima
Yasuyuki
Y
Miyazaki
Shigeru
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006651:Histocytochemistry / Q000662:veterinary; D020287:In Situ Nick-End Labeling / Q000662:veterinary; D008099:Liver / Q000187:drug effects* / Q000276:immunology; D008221:Lymphoid Tissue / Q000187:drug effects* / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D013047:Specific Pathogen-Free Organisms; D013552:Swine / Q000276:immunology*; D014255:Trichothecenes / Q000633:toxicity*
D016207:Cytokines; D012333:RNA, Messenger; D014255:Trichothecenes; C007262:deoxynivalenol
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