The effect of natural toxicants and other chemicals on the kidney.

Repeated administration of ochratoxin A (OTA) caused renal morphological dose-related changes, that were associated with proximal tubular and glomerular damage the latter showing oedema and prominent PAS staining suggestive of glomerular basement membrane thickening. On the other hand, the combined administration of repeated doses of OTA and aflatoxin B[1] (2. 5 mg and 100 ug per kg, respectively), appeared to have a synergistic effect, characterized by severe disruption of proximal tubules and general morphological derrangement of the glomerulus, involving intense and faint staining nuclei (suggestive of cell necrosis) and cytoplasmic vacuolation, which was not seen with either toxin alone. When clinical biochemical parameters were measured after repeated administration of a low dose of OTA, enzymuria, glucosuria, polyuria and proteinuria were observed, with glucose and alkaline phosphatase as the most sensitive parameters. Metabolic studies performed in vitro showed that isolated pig and rat glomeruli incorporate different amino acids linearly for several hours at different rates and perform oxidative metabolism of glucose and fatty acids to CO[2] also linearly. For pig glomeruli the order of amino acid incorporation was LEU >> PRO = HIS > LYS > GLY and for rat glomeruli it was TRP >> PHE > TYR = LEU > PRO > HIS. The same amino acids were incorporated in a similar way in rat tubules, but the incorporation rate is 10-fold lower. When de novo synthesis of protein by pig glomeruli exposed to different chemicals was assessed, using proline (PRO) as the precursor, adriamycin (ADR) and ethacrynic acid (ETA) inhibited protein synthesis more than 2-bromoethanamine (BEA) and streptomycin (STR), and much more than puromycin aminonucleoside (PAN). When isolated rat glomeruli were exposed to low concentrations of OTA, there was a generalized inhibition on de novo synthesis of protein from the six amino acids tested and the aromatic amino acids (TRP, TYR and PHE) were more sensitive to OTA effect than PRO. Low concentrations of OTA (10 - 100 uM) enhanced glomerular and tubular glucose metabolism to CO[2] and only high concentrations of the mycotoxin (1000 uM) caused significant inhibition of glomerular and proximal tubular linolenic acid metabolism