o,P'-DDD, a derivative of insecticide DDT, which reveals the toxicity and adrenostatic effet by cortisol biosynthesis in the zona fasciculata of adrenal cortex has been used for the treatment of unoperable adrenocortical carcinoma. Adverse effects of ...
o,P'-DDD, a derivative of insecticide DDT, which reveals the toxicity and adrenostatic effet by cortisol biosynthesis in the zona fasciculata of adrenal cortex has been used for the treatment of unoperable adrenocortical carcinoma. Adverse effects of o,P'-DDD were usually dose-related and reversible. Most untoward effects include gastrointestinal disturbances, neuromuscular disorders, depression of central nervous system and skin rash but there is a few reports on its nephrotoxicities.
o,P'-DDD in corn oil was administered orally to rats for 28 days to investigate its nephrotoxicity by observation of the ultrastructural changes and immunoglobulin deposition in renal glomeuli.
The results obtained were as follows.
1. The ultimate destructive target of intracytoplasmic organelle in endothelium and epithelium of renal glomeruli was mitochondria. The severity of the mitochondrial alterations was dependent of the dosages of o,p'-DDD.
2. The characteristic ultrastructural changes in endothelium of glomerular capillary were swelling and detachment from underlying basement membrane. The splitting and complete separations between endothelium and basement membrane were observed in more advanced lesions by the increased dosage of administration of o,p'-DDD and basement membrane in capillary wall of renal glomeruli was irregular and partly thickened.
3. Amorphous double ring formation, electron dense deposits and multiple myelin figures in mitochondria were characteristic ultrastructural findings in the epithelium of glomeruli.
4. Ig G and Ig M depositions were clearly observed in the capillary lumen, subendothelial area and epithelial cells of proximal convoluted tubule. These depositions were more prominent by the increased of o,p'-DDD dosage.
From the above results it is suggested that o,P'-DDD exhibits nephrotoxicity by mitochondrial destruction in epithelium and endothelium of glomerular capillary and the severity of mitochondrial alterations was dose dependent of o,p'-DDD.