Alterações histológicas dos rins e expressão das metalotioneínas e das proteínas de choque térmico em ratos Wistar após exposição ao fungicida tirame / Kidney histological alterations and metallothionein and heat shock protein expression in Wistar rats after fungicide thiram exposure

Avaliaram-se as alterações histológicas e a expressão das metalotioneínas (MTs) e das proteínas de choque térmico (Hsp70) nos rins de ratos Wistar após a exposição ao fungicida tirame. Os animais foram distribuídos em três grupos: grupo dieta-padrão; grupo dieta-padrão+óleo de milho; e grupo tirame. Foram encontradas diferenças significativas (P<0,05) na evolução do peso corporal entre os ratos do grupo tirame e os dos grupos controle e óleo de milho, e não foram verificadas lesões histológicas evidentes nos rins dos animais. Foram encontradas diferenças entre os animais do grupo exposto ao tirame e os dos grupos controle e óleo quanto às características histomorfométricas relativas ao corpúsculo renal - exceto para a proporção área da cápsula de Bowman:área do glomérulo - e relativas aos túbulos contorcidos proximal e distal - exceto para altura do epitélio dos túbulos distais. Nos ratos expostos ao tirame, foi observada imunomarcação positiva para as MTs, de moderada a forte, nos túbulos contorcidos da região cortical, diminuindo do córtex em direção à medula, e forte imunomarcação para as Hsp70 nas áreas do córtex e da medula, no glomérulo e nos túbulos contorcidos. Os resultados sugerem que o tirame pode ter toxicidade crônica nos mamíferos por afetar o seu crescimento e que a expressão das MTs e das Hsp70, provável resposta celular adaptativa ao estresse oxidativo causado pelo tirame, pode ser utilizada como biomarcador de exposição a este químico.

The histological alterations and the expression of metallothionein (MTs) and heat shock protein (Hsp70) in the kidney of Wistar rats after thiram fungicide exposure were evaluated. Animals were distributed into three groups: standard diet group, standard diet + corn oil group and thiram group. Significant differences were found (P<0,05) in the evolution of body weight between rats in the thiram group and those in the control and corn oil groups, and no histological lesions were evident in the animals' kidneys. Differences were found among animals in the group exposed to thiram and the control and oil groups regarding histomorphometric characteristics of the renal corpuscle - except for the proportion in the area of Bowman's capsule: glomerulus area - and regarding the height of the epitelium in the distal tubules. In rats exposed to thiram, a positive moderate to strong immunoexpression was observed for MTs, in the cortical convulated tubules decreasing the cortex towards the medulla, and a strong immunoexpression for Hsp70 in the cortex and medulla areas, in the glomerulus and convulated tubules. The results suggest that thiram may have chronic toxicity in mammals affecting their growth, and that the expression of MTs and Hsp70, a probable cellular adaptive response to the oxidative stress caused by thiram, may be used as a biomarker of exposure to this chemical.

Palatal abnormalities in the developing rat induced by retinoic acid

Palatogenesis is a complex developmental processthat requires two main events: elevation andthen fusion of the palatal shelves. These processesare disrupted by teratogens such as retinoicacid (RA) and genetic defects, resulting in variousmalformations (including cleft palate). Usinghistological and immunohistochemical techniques,the effects of different isomers of RA, administeredin various concentrations to pregnantrats on different gestational days (GD), were assessedfrom observations of the state of palataldevelopment on GD 18 in foetuses without exencephaly.Varying degrees of clefting of thepalate were observed, from failure of elevationof the palatal shelves to failure of fusion in themidline. This study shows that all-trans-RA isthe most teratogenic RA isomer in terms of ratpalatal abnormalities. It also supports previousfindings that the timing of administration of alltrans-RA is more critical than the concentration,with treatment between GD 10 and 10.5 havingthe most severe effects. Previous histologicalstudies also suggested that RA is associatedwith the appearance of ectopic cartilages withinthe developing palate of foetuses showing exencephaly.In this investigation, immunohistochemicallabelling of the foetal material with antibodiesthat recognise epitopes present in linkproteins 1, 2, and 3 (8A4), chondroitin-4-sulphatestubs (2B6), and G1 and chondroitin sulphateattachments (7D1) present in aggrecan (associatedwith hyaluronan in cartilage) showedno signs of ectopic cartilage formation within the palate at GD18. Internal controls of the cartilagesof the nasal septum, vomeronasal cartilage, andMerkel’s cartilage labelled intensely and appearedmorphologically normal (AU)

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Transverse vaginal septum in the specific-pathogen-free Wistar rat.

A transverse vaginal septum was found in 2% of a substrain of specific-pathogen-free Wistar rats used in reproductive toxicity studies. Macroscopic observation mostly revealed a complete transverse septum. In a few rats an incomplete septum with a small central pupillary gap was found. Microscopically the septum consisted of a central core of connective tissue covered on both sides by epithelium. The rats with vaginal defects were clinically healthy but were unable to breed because the vaginal septum hampered the progress of the spermatozoa. Cranial to the defect, the uterus, cervix, and cranial portion of the vagina were moderately to severely dilated and often filled with mucopurulent fluid and cellular debris. The presence of a transverse vaginal septum is rare in rats and can therefore be easily missed. Congenital, embryologic, and histologic aspects of this anomaly are discussed and compared with existing literature data.