Effects of Hypoxia and Environmental Agents on Renal Tubules with a Scope of Combined Effect

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When we assess the combined effect of plural agents in the experimental animals for extrapolation to human, the data eliciting mechanisms about their interactions in the living organ are obviously helpful. Thus, we have developed in vivo scanning reflectance spectrophotometry and in vivo surface fluorometry for this purpose of the real-time observation of intracellular biochemical changes in order to apply the techniques to the studies in environmental and occupational toxicology in rabbit proximal renal tubules and in perfused rat kidney. The release of lactate dehydrogenase (LDH) was measured as an index of plasma membrane damage. The cellular contents of K and Ca were also measured. Ca content decreased slightly during anoxia, but increased up to fourfold during severe hypoxia. The degree of respiratory impairment was identical during anoxia or hypoxia, suggesting that Ca accumulation was not associated with the impairment. Decreasing the extracellutar Ca to 2.5 <micrn> decreased LDH release significantly during anoxia, suggesting that plasma membrane damage during anoxia may be associated with increased intracellular free Ca. Effects of organic solvents on cell injury were assessed in the tubular cell supsension with a scope of combined effect. The organic solvents employed in this study increased oxygen consumption in the tubular cells at its low concentrations, whereas they decreased the oxygen consuption at relatively high concentrations. Both bubular cell suspension and perfused kindney in the present study were considered as an experimental model for assessment of combined effects of plural environmental agents.