Hepatic hyperplasia and damages induces by zearalenone Fusarium mycotoxins in BALB/c mice / Hiperplasia e danos hepáticos induzidos por micotoxinas do gênero Fusarium-zearalenone em camundongos BAB/c

CONTEXT: Zearalenone is a mycoestrogen and considered a mycotoxin. OBJECTIVE: To establish whether zearalenone produced hepatotoxicity via oral administration. METHODS: Zearalenone was orally administered at a dose of 50 mg, 100 mg and 200 mg ZEN/body weight/daily, respectively, for 14 days to three groups of BALB/c mice. Diagnostic modalities used to evaluate hepatic damage and impaired hepatic function pre- and post zearalenone administration included hepatic marker enzyme activity, pentobarbital sleeping time, cytochrome P-450 activities and histopathologic evaluation of liver. RESULTS: Significant histopathologic changes viz. sinusoidal congestion, cytoplasmic vacuolization, hepatocellular necrosis and neutrophil infiltration were observed after evaluating of liver section from each group after accumulated zearalenone exposure. Further, zearalenone exposure increased activities of alanine transaminase, aspartate transaminase and lipid peroxides whereas activities of tissue glutathione and cytochrome P450 were decreased as compared to control mice. Zearalenone also increased the sleeping time and decreased sleeping latency after pentobarbital through intraperitoneal route as compared to control mice which indicates that the impairment of hepatic metabolizing enzymes by zearalenone. CONCLUSION: Zearalenone is a potential hepatotoxin by oral route.

CONTEXTO: Zearalenone é um micoestrógeno e considerado como micotoxina. OBJETIVO: Avaliar se o Zearalenone produz hepatotoxicidade por administração via oral. MÉTODOS: Zearalenone foi administrada por via oral em doses de 50 µg, 100 µg e 200 µg/peso corporal/dia/14 dias, respectivamente, para três grupos de camundongos BAB/C. Modalidades diagnósticas usadas para avaliar o dano hepático e comprometimento da função hepática pré- e pós-administração de Zearalenone incluíram atividade enzimática de marcadores hepáticos, tempo de sono por pentobarbital, atividade do citocromo P-450 e avaliação histopatológica hepática. RESULTADOS: Alterações histopatológicas significantes como congestão sinusoidal, vacuolização citoplasmática, necrose hepatocelular e infiltração neutrofílica foram observadas após avaliação histológica de cada grupo após exposição acumulada de Zearalenone. Além disto, a exposição à Zearalenone incrementou a atividade das enzimas alanina transaminase e aspartato transaminase e peróxidos lipídicos, ao passo que as atividades teciduais de glutationa e citocromo P-450 diminuiram, quando comparadas com camundongos-controle. Zearalenone também aumentou o tempo de sono e diminuiu a latência do sono após a administração de pentobarbital por via intra-abdominal, quando comparados com camundongos-controle, o que indica o comprometimento das enzimas do metabolismo hepático por ela. CONCLUSÃO: Zearalenone é uma potente hepatotoxina quando administrada por via oral.

Morphological changes induced by testosterone in the mammary glands of female Wistar rats

Increased levels of androgens in postmenopausal women are considered to be a risk factor for breast cancer. Testosterone, alone or in combination with estrogen, induces epithelial dysplasia and mammary tumors in Noble rats. Since this model of hormone-induced neoplasia has not been reported in other rat strains, we studied the effect of testosterone on the mammary gland morphology of female Wistar rats. Sixty adult, non-castrated, female Wistar rats were implanted in the dorsum midline with a silicone tube containing 50 mg testosterone (testosterone propionate in 30 animals and non-esterified testosterone in the remaining 30 animals) and 20 additional animals were implanted with empty tubes and used as control. Five animals per group were killed 30, 60, 90, 120, 150, and 180 days after implantation, and the mammary glands were dissected, fixed and embedded in paraffin. Histological sections were then stained with hematoxylin and eosin and picrosyrius red for collagen visualization. Morphological and morphometric analysis demonstrated ductal proliferation and acinotubular differentiation with secretory activity in all treated animals, peaking at 90 days of androgen exposure. After 90 days the proliferation of acinar epithelial cells was evident, but there was a progressive reduction of secretory differentiation and an increase in intralobular collagen fibers. There was no morphological evidence of dysplastic changes or other pre-neoplastic lesions. Testosterone treatment applied to adult, non-castrated female Wistar rats induced a mammary gland hyperplasia resembling the lactating differentiation, with progressive reduction in secretory differentiation.

Estudio histológico e histoquímico de lesiones hiperplásicas y displásicas del intestino grueso en Cebus Apella (primate) tratado con 1, 2-dimetilhidrazida / Histological and histochemical study of hyperplastic and dysplastic lesions of the large intestine in Cebus Apella (primate) treated with 1, 2-dimethylhydrazine

El principal objetivo del presente trabajo consistió en determinar los cambios histológicos en el epitelio del colon en primates de la especie Cebus apella inducidos mediante la administración de la 1,2-dimetilhidrazina (DMH). Fueron utilizados 12 primates, machos de 30 meses de edad y con un peso promedio de 2,800Kg. La DMH fue administrada por vía subcutánea a razón de 25 mg/Kg de peso corporal semanalmente, durante 16 semanas. Durante los 20 meses que duró la experiencia el peso corporal fue evaluado semanalmente en los primeros 4 meses y cada 30 días hasta el final del experimento. Al final de la experiencia, en cortes histológicos de 5 mum, coloreados con Hematoxilina-Eosina, fueron evaluados los cambios histológicos del epitelio intestinal, así como las mucosustancias, utilizándose las técnicas del PAS y Alcian blue e pH 2,5. El estudio histológico e histoquímico permitió caracterizar la morfología normal, así como las características de las mucosustancias en tres regiones: ciego, colon transverso y colon distal. Los cambios histológicos observados en los animales tratados con DMH consistieron en fenómenos de hiperplasia, displasia y disminución de las mucosustancias. Los cambios hiperplásicos comprometieron a las criptas glandulares y al epitelio superficial que reviste a los nódulos linfoides. Focos de displasia fueron observados en el colon transverso y última porción del colon distal y comprometieron a criptas localizadas tanto en profundidad como en criptas de la mucosa superficial. Se observaron criptas con disminución de mucosustancias neutras y ácidas. Nuestros resultados sugieren que la DMH indujo en el colon, focos displásicos y lesiones hiperplásicas en criptas y en el epitelio que reviste a los nódulos linfoides, así como disminución de las mucosustancias neutras y ácidas.

Hiperplasia linfoide cervical por difenilhidantoína / Cervical lymphoid hyperplasia due to phenytoin

We present the case of a three year old girl who showed two adverse reactions to DPH, one of them a large cervical lymphatic hyperplasia, which responded to discontinuation of the drug. Laboratory tests were normal and histological examination showed non specific adenitis. We discuss this unusual case and the importance of the cervical adenopathy differential diagnosis