T-2 Toxin and Apoptosis

Abstract

T-2 toxin is a cytotoxic fungal secondary metabolite produced by various species of Fusarium. This paper reviews the reported data about the development and/or mechanisms of T-2 toxin-induced apoptosis in the hematopoietic, lymphoid and gastrointestinal tissues, dorsal skin and fetal tissues of mice and rats. Apoptosis occurs earlier in hematopoietic tissues than in lymphoid tissues, and moreover there is a difference among lymphocyte populations in the susceptibility to T-2 toxin. C-fos plays an important role in the early phase of T-2 toxin-induced apoptosis in hematopoietic and lymphoid tissues through mobilization of [Ca 2+ ] i and the PKC-dependent pathway, but not through Fas/Fasligand or p53-related pathways. In the gastrointestinal tract, apoptosis develops earlier in the small intestine than in the stomach, and is more prominent in the small intestine than in the large intestine. In the dorsal skin topically treated with T-2 toxin, epidermal basal cell proliferating activity is first suppressed due to the elevated TGF-β 1 expression, and then basal cell apoptosis develops concomitantly with the elevation of c-fos, c-jun and TNF-α mRNAs expression. In the fetuses, T-2 toxin-induced apoptosis is mainly observed in the central nervous and skeletal systems. In the fetal brain, T-2 toxin induces oxidative stress, followed by activation of the MAPK-JNK-c-Jun pathway, finally resulting in apoptosis. The TNF receptor pathway may also be involved in T-2 toxin-induced apoptosis in the fetal brain. Thus, the development and mechanisms of T-2 toxin-induced apoptosis differ somewhat depending on the tissues affected. (J Toxicol Pathol 2006; 19: 15-27)

Scientific Opinion on the risks for animal and public health related to the presence of T-2 and HT-2 toxin in food and feed

“…DNA damage could be a secondary effect of protein synthesis inhibition or oxidative stress that can in turn activate mitochondrial apoptotic pathways. Moreover T-2 toxin increases the expression of p53, a pivotal apoptotic protein, and other proteins such as Bax, Bcl-2, cytochrome-c involved in mitochondrial apoptotic pathway (Doi et al, 2006;Chaudhari et al, 2009a). As mentioned earlier, various studies report the release of pro-apoptotic factors from mitochondria and increased activity of specific proteases executing this specific apoptotic program.…”

“…The plasma radioactivity after oral administration of 3 H-T-2 toxin to mice peaked after 30 minutes and T-2 toxin is rapidly metabolised and excreted in faeces and urine (Matsumoto et al, 1978;Doi et al, 2006;Wu et al, 2010). The plasma radioactivity after oral administration of 3 H-T-2 toxin to mice peaked after 30 minutes and T-2 toxin is rapidly metabolised and excreted in faeces and urine (Matsumoto et al, 1978;Doi et al, 2006;Wu et al, 2010).…”

Evaluation of Myelotoxicity in Dietary Restricted Rats

“…Changes in the lymphoid organs due to immunotoxicants appear as a decrease in the blood cell count 21,22 . Mature granulocytes are not significantly affected; however, cytotoxic fungal metabolites have been shown to cause a decrease in the immature myelocyte count 23 . Decreases in blood cell counts and bone marrow hypoplasia are well known to be caused by 5-FU administration 18–20 .…”

Endoplasmic reticulum stress is involved in the T‐2 toxin‐induced apoptosis in goat endometrium epithelial cells

“…The detailed mechanism of the late effects of T-2 toxin on EECs requires further study. In the fetal brain, T-2 toxin induces oxidative stress, followed by activation of the MAPK-JNK-c-Jun pathway, finally resulting in apoptosis (Doi, Shinozuka, & Sehata, 2006). The apoptosis of chondrocyte induced by T-2 toxin involved the increased levels of ATF2, JNK and p38 mRNAs and related protein expression (Han & Guo, 2013).…”