Difference in susceptibility to experimental thiophene poisoning between spontaneously hypertensive and wistar-kyoto rats.

Abstract

Many of the patients with Minamata disease, caused by methylmercury have developed hypertension. In experimental methylmercury poisoning, the level of mercury and the mortality are higher in spontaneously hypertensive rats (SHR) than in Wistar-Kyoto rats (WKY). Thiophene induces cerebellar degeneration, which is also found in rats with methylmercury poisoning and hepatic necrosis. To clarify the pathophysiology of the thiophene-induced lesions female SHR and WKY aged 150 days were studied and a comparison was made between the two strains. Up to an age of 150 days, the body weight of SHR was less than that of WKY, but food consumption by SHR was higher than that of WKY. SHR were more susceptible to thiophene poisoning than WKY in terms of symptoms, changes in auditory brainstem response (ABR), and histopathological findings. Administration of pentobarbital was more effective in producing hepatic lesions in SHR than in WKY. Ultrastructurally, nuclear chromatin segregation and irregular distribution of rough endoplasmic reticulum (rER) were prominent in the hepatic cells of non-treated SHR. An osmiophilic homogeneous substance appeared to play an important role in the formation of cerebellar lesions in both SHR and WKY. The hepatic injury and disturbance of cerebellar blood vessels seem to cause the cerebellar lesions. It is suggested that a reduced ability for drug metabolism in SHR, which might be inherited or acquired, is one of the causes of the higher susceptibility of this strain to thiphene poisoning, compared with WKY.