2,3,7,8-Tetrachlorodibenzo-p-dioxin Promotes Proliferation of Astrocyte Cells via the Akt/STAT3/Cyclin D1 Pathway / 生物医学与环境科学（英文）

OBJECTIVE@#The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a persistent organic pollutant, is harmful to the nervous system, but its effects on the brain are still unclear. This study aimed to investigate the effects of TCDD on astrocytes proliferation and underlying molecular mechanism.@*METHODS@#The cell proliferation was measured by EdU-based proliferation assay and PI staining by flow cytometry. Protein expression levels were detected by Western blotting. Immunofluorescence, cytoplasmic and nuclear fractions separation were used to assess the distribution of signal transducer and activator of transcription 3 (STAT3).@*RESULTS@#C6 cells treated with 10 and 50 nmol/L TCDD for 24 h showed significant promotion of the proliferation of. The exposure to TCDD resulted in the upregulation in the expression levels of phosphorylated protein kinase B (p-Akt), phosphorylated STAT3, and cyclin D1 in a dose- and time-dependent manner. The inhibition of Akt expression with LY294002 or STAT3 expression with AG490 abolished the TCDD-induced cyclin D1 upregulation and cell proliferation. Furthermore, LY294002 suppressed the activation of STAT3. Finally, TCDD promoted the translocation of STAT3 from the cytoplasm to the nucleus, and LY294002 treatment blocked this effect.@*CONCLUSION@#TCDD exposure promotes the proliferation of astrocyte cells via the Akt/STAT3/cyclin D1 pathway, leading to astrogliosis.

Beta-glucan prevents toxic effects of 2, 3, 7, 8-TCDD in terms of oxidative and histopathological damage in heart tissue of rats

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental contaminant which causes severe toxic effects. Despite there is some suggestion concerning with TCDD induced cardiotoxicity such as formation of free radicals, the main mechanism has not been entirely explained. Beta-glucan is known as strong antioxidant matter and can scavenge free radicals. Therefore this study aimed to investigate the protective effects of beta-glucan against TCDD induced cardiotoxicity in rats. In this study, 2-3 months of age and 190-250 g in weight 32 rats were randomly divided into four equal groups (n=8 for each group). Group 1 was control; Group 2 was TCDD group (2 µg/kg/week); group 3 was the beta-glucan group(50 mg/kg/day), and group 4 was TCDD and beta-glucan treatment group. The heart samples were taken from rats after 21 days treatment. The results were shown that Despite TCDD exposure visibly caused to increase (p ≤ 0.001) in TBARS levels, It caused a visible decline in the levels of GSH, CAT, GSH-Px, and SOD. However Beta glucan significantly increased GSH, CAT, GSH-Px, SOD levels and decreased generation of TBARS. Additionally, our histopathological observations were in agreement with the biochemical results. In conclusion, Beta-glucan treatment exhibited protective activity on TCDD induced cardiotoxicity

Reproductive Development and Pulmonary CYP1A1 Levels in Mice Offspring Exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) During Lactation / 环境与健康杂志

Objective To explore the effect of lactational TCDD exposure alone on growing development and cytochrome P4501A1(CYP1A1) in mice offspring. Methods Mature Kunming mice (clean animal,No.604017) were divided to 2 treatment groups (40 and 20 ?g /kg bw TCDD),2 vehicle controls and 1 normal control. There were 3 maternal mice and 25-28 pups in each group. Maternal mice were administered TCDD by intraperitoneal injection in three times on post-parturition days 1,3,5,and the mice offspring were exposed to TCDD by maternal milk. The changes of body weight and the development of reproductive system were observed. The pups were sacrificed on postnatal days (PND) 35,and CYP1A1 expression in the lungs of mice offspring were measured by immunohistochemistry. Results The average body weight of mice offspring in 2 TCDD treatments decreased significantly from PND14 (P

Pathologic Comparative Studies on the Protective Effects by Panax Ginseng and Panax Quinquefolium for Treating 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced Toxicity in Male Rats

BACKGROUND: Panax ginseng is known to decrease the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced testicular toxicity. Thus, we aimed to reveal the differences between Panax ginseng and Panax quinquefolium extract for their effects on TCDD-induced toxicity. METHODS: Forty rats were divided into four groups; the control group, the TCDD only group, the TCDD plus Panax ginseng group, and the TCDD plus Panax quinquefolium-treated groups. Ginseng extract was given orally to rats from day one to twenty-one. TCDD was intraperitoneally administered to rats at a single dose of 50 microgram/kg on the seventh day. The pathologic changes were then examined. The changes of body weight, cholesterol and GOT in the serum were also examined. RESULTS: The TCDD toxicity was prominent in the thymus, liver and testis. The thymus showed atrophy and an inverse pattern of lymphocyte density in the cortex and medulla. The liver revealed central necrosis with fatty changes. On electron microscopy, the seminiferous tubules showed destruction of the spermatogonia, clear spaces or vacuolar changes and degeneration in the Sertoli cells or germ cells. The above mentioned TCDD-induced changes were reduced in the rats that were administered with Panax ginseng, whereas Panax quinquefolium did not reduce these changes. CONCLUSION: The protective effects of Panax ginseng on the TCDD-induced toxicity were more effective than those of Panax quinquefolium.

A Case of Incidental Epidermolytic Hyperkeratosis Occurring Normal Looking Skin Adjacent to Folliculitic Papules: In Veterans Who Participated in Vietnam War

On histological examination, an epidermolytic hyperkeratosis was observed adjacent to follicular papules on the back of a 53-year-old man. It has been reported that incidental epidermolytic hyperkeratosis occur either within various lesion (epidermal neoplasm, melanocytic neoplasm, scars, and inflammatory conditions) or in the normal skin adjacent to the lesion. This patient participated in the Vietnam War for 2 years, and had had contact with defoliants. He was treated for multiple peripheral neuropathies and cerebral infarcts. In keratinocytes, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; Agent Orange) contained in defoliating agents is associated with altered patterns of keratinocyte differentiation. So, as a cause of incidental epidermolytic hyperkeratosis, defoliant contact could be suspected.