Direct effect of p, p'-DDT on mice liver

ABSTRACT Contact with the pesticide dichlorodiphenyltrichloroethane (p,p′-DDT) can be the cause of various harmful effects in humans, wildlife, and the environment. This pesticide is known to be persistent, lipophilic, resistant to degradation, and bioaccumulive in the environment and to be slowly released into bloodstream. Growing evidence shows that exposure to DDT is linked to type 2 diabetes mellitus. Individuals exposed to elevated levels of DDT and its metabolite have an increased prevalence of diabetes and insulin resistance. To evaluate these possible relationships, experiments were performed on eight-week-old female mice, divided into three groups (n = 10 per group): Group 1 received a vehicle-control intraperitoneal (i.p.) injection of sesame oil; Groups 2 and 3 received an i.p. dose of 50 and 100 µg/g p,p′-DDT respectively, dissolved in sesame oil. All groups were treated once daily for four days. Real-time PCR analysis of several genes was undertaken. Additionally, biochemical parameters and histopathological changes were measured. NQO1, HMOX1, NR1I3 and NR3C1 were up-regulated in DDT-exposed animals compared to the vehicle control group, while only SREBP1 was down-regulated in the 100 µg/g group. MTTP and FABP5, not previously reported for DDT exposure, but involved in regulation of fatty acid fluxes, could also function as biomarkers cross-talking between these signaling pathways. These results suggest that beyond epidemiological data, there is increasing molecular evidence that DDT may mimic different processes involved in diabetes and insulin resistance pathways.

RESUMO O contato com o praguicida diclorodifeniltricloroetano (p, p'-DDT) pode ser a causa de vários efeitos nocivos sobre os seres humanos, animais silvestres e o meio ambiente. Sabe-se de sua característica de bioacumulação, ser altamente persistente no meio ambiente, lipofílico, resistente à degradação e lentamente liberado na corrente sanguínea. Existe uma evidência crescente de que a exposição ao DDT pode ser ligada a Diabetes mellitus tipo 2. Os indivíduos expostos a níveis elevados de DDT e seu metabólito apresentam maior prevalência de diabetes e resistência à insulina. A fim de obter informações sobre essas possíveis relações, camundongos fêmeas de oito semanas de idade foram divididos em três grupos (n = 10 por grupo): Grupo 1 recebeu um veículo de óleo de gergelim via i.p.; os Grupos 2 e 3 receberam, via i.p., 50 e 100 µg/g de p, p'-DDT, respectivamente, dissolvidos em óleo de gergelim. Todos os grupos foram tratados uma vez ao dia durante quatro dias. Além da análise de PCR em Tempo Real de vários genes, os parâmetros bioquímicos e alterações histopatológicas também foram medidos. A expressão gênica do mRNA dos genes NQO1, HMOX1, NR1I3 e NR3C1 foi maior nos animais expostos ao DDT, em comparação ao grupo controle, enquanto a expressão gênica do SREBP1 diminuiu na concentração de 100 µg/g. Os genes MTTP e FABP5 envolvidos na regulação do fluxo de ácidos graxos, embora não estudados quanto à exposição ao DDT, também podem funcionar como biomarcadores de resposta cruzada entre essas vias de sinalização. Esses resultados sugerem que, além de dados epidemiológicos, há cada vez mais evidências moleculares de que o DDT poderia, de fato, imitar diferentes processos que envolvem as rotas de diabetes e de resistência à insulina.

Association between Serum Gamma-Glutamyl Transferase and Thyroid Cancer in an Ultrasonographically Screened Population / 대한갑상선학회지

BACKGROUND AND OBJECTIVES: We reported recently a positive correlation between obesity and thyroid cancer in women. Serum gamma-glutamyl transferase (GGT) is regarded as a marker of exposure to environmental pollutants, cancer-causing xenobiotic. This study was conducted to evaluate the mechanism behind the association of obesity with thyroid cancer. We hypothesized serum GGT may be a surrogate for persistent organic pollutants to explain the connection between obesity and thyroid cancer. MATERIALS AND METHODS: We obtained data from 15,131 subjects who underwent a routine health checkup including thyroid ultrasonography from 2007 to 2008 at the Health Screening and Promotion Center of Asan Medical Center. Suspicious nodules were examined by ultrasonography-guided aspiration. Those with a history of hepatobiliary disease and abnormal result of liver function test were excluded. Serum GGT cut-off points were the 25th, 50th, and 75th sex-specific percentiles. RESULTS: A total of 15,131 subjects (7662 men and 7469 women) were screened by thyroid ultrasonography. Thyroid cancers were diagnosed in 260 patients. After adjustment of age, smoking status, alcohol intake, body mass index, compared with the lowest serum GGT quartile, odds ratios (95% confidence intervals) of risk of thyroid cancer were 0.54 (0.28-0.99) for 2nd quartile, 0.92 (0.56-1.50) for 3rd quartile, and 0.61 (0.34-1.09) for 4th quartile in men. In women, the adjusted odds ratios were 1.06 (0.66-1.72), 1.18 (0.77-1.85), and 0.63 (0.38-1.06) for the 2nd, 3rd, and 4th quartile, respectively. CONCLUSION: Elevated GGT is not associated with a higher prevalence of thyroid cancer in either gender when evaluated in a routine health checkup setting.

Mechanism of rat testis toxicity induced by organic extract from Jialing river water / 第三军医大学学报

Objective To study the toxicity of organic extract from river water on the male reproductive system in rats.Methods Organic pollutants were extracted from river water with XAD-2 resin and the extract from 2,16 and 80 L river water was administered daily into 30 male SD rats by gavage for consecutive 28 days.Corn oil served as the solvent control in another ten rats.After the last intake of water extract,all rats were killed,and the sections of testis were prepared according to routine procedure.The TUNEL assay for in situ detection of apoptosis and quantitation of apoptotic germ were performed on testicular sections.Immunohistochemistry and Western blotting were used to examine the changes of scf,fas,fasL and c-kit expressions in rat testis.Results The percentage of apoptotic spermatid cells significantly increased in rats receiving organic extract from 80 L water daily,as compared with the control rats.The spermatocytes in rats receiving organic extract from 80 L water daily overexpressed fas,fasL and c-kit.Conclusion The organic pollutants from river water result in spermatid apoptosis and spermatogenesis arrest.