Abstract
The present authors attempted to determine whether nephrotoxicity could be produced in fetal rats via injection of glutamate into amniotic sacs at a late stage in gestation. Glutamate is both an excitatory neurotransmitter and a neurotoxin. We used enzyme histochemistry to determine whether any alteration of alkaline phosphatase (ALPase) activity, an index of nephrotoxity, occurred in the kidneys of fetal and postnatal rats. Glutamate or saline were injected into the amniotic sacs of fetal rats on the 15th day of gestation. Three hours and 2, 5 and 34 days after administration of glutamate, saline or nothing(control), the kidneys of fetal and postnatal rats were removed, ALPase histochemistry was performed and the tissue was observed under light and electron microscopy. The results showed that at 3 hours and 2 days (17th day of gestation), in glutamate treated and control fetal rats, ALPase activity was localized to a few tubules in the inner cortex of the kidney. Intensity of ALPase activity was weak in both glutamate treated and control fetal rats. No differences were observed with regard to ALPase activity between the two groups. At 5 days (20th day of gestation), ALPase activity was localized to a few proximal tubules in the inner cortex of the kidney and the observed intensity was weak in glutamate treated fetal rats, whereas in control fetal rats, activity was detected in numerous proximal tubules throughout the entire inner cortex of the kidney and the observed intensity was strong. At 34 days (28th postnatal day), ALPase activity was detected in numerous proximal tubules throughout the entire cortex of the kidney and the observed intensity was strong in both glutamate treated and control rats. No differences were observed with regard to ALPase activity between the two groups. These results suggested that the observed functional disorder, namely nephrotoxicity of the proximal tubules of fetal kidney at 5 days after administration of glutamate, which was detected as a diminution of ALPase activity, might have been caused by temporary glutamate exposure during a late stage in gestation. Moreover, proximal tubules of the kidney that had suffered glutamate damage showed a recovery of function at 34 days after the glutamate treatment. Given that the changes in ALPase activity in the proximal tubules at 5 days after treatment of glutamate preceded morphological changes. ALPase histochemistry may be useful as an early and sensitive index of nephrotoxicity during renal development.
