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 single-stranded DNA and cleaved caspase-3. The number of TUNEL-positive 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.
Animals ; Apoptosis/*drug effects/immunology ; Cytokines/*biosynthesis/genetics ; Gene Expression Regulation/drug effects ; Histocytochemistry/veterinary ; In Situ Nick-End Labeling/veterinary ; Liver/*drug effects/immunology ; Lymphoid Tissue/*drug effects/immunology ; RNA, Messenger/*biosynthesis/genetics/immunology ; Reverse Transcriptase Polymerase Chain Reaction/veterinary ; Specific Pathogen-Free Organisms ; Swine/*immunology ; Trichothecenes/*toxicity

The 38-years old woman was hospitalized due to peritonitis carcinomatosa after 8 months, since the operation for advanced gastric cancer. Although the dosage of domperidone suppository, metoclopramide injection and haloperidol injection was started to prevent her from vomiting, it was stopped because of the complication of extrapyramidal symptoms. Instead of previous prescription, the traditional Japanese medicine, ice candy of rikkunshito, was prepared and started to give her. After its dosage, the number of vomit was gradually decreased, and she was permitted to go back her home. Before a dosage of ice candy of rikkunshito, it was impossible for her to eat orally even if she felt hungry and had appetite, which caused a strong grief to her. Ice candy of rikkunshito is a smooth medicine and expected to prevent from vomiting while an intake of ice candy orally. Hence, it is considered that there is possibility to have effectiveness both physically and psychologically. After few days from going back home, she caused a consciousness impediment. Her last stay at home was only few hours. After one month since then, she died leaving her message,“I was tired out, but happy to stay at my home.”