Enhancement of maternal and fetal nephrotoxicity of salicylate by zinc deficiency. Morphological, enzyme histochemical and immunohistochemical studies.
An oral dose of 700 mg/kg salicylic acid was given to normal and Zn-deficient rats at day 16 of gestation. Maternal and fetal kidneys were studied at day 19 of gestation. Zn-deficiency did not cause any lesions detectable by semi-thin section light microscopy, electron microscopy, enzyme histochemistry and immunohistochemistry. Salicylate may lead only to small morphological, enzymatic and cytoskeletal defects in the maternal and fetal kidney. However, enzyme activities decreased in plasma membranes, mitochondria, lysosomes, endoplasmic reticulum and peroxisomes in all segments of the tubular apparatus when salicylate was given to Zn-deficient rats. Cytoskeletal proteins such as keratin in the glomerular cells and epithelial lining of the collecting ducts and vimentin in vascular endothelial cells of the maternal kidney were also affected. In addition, the epithelial cells of the collecting ducts, which were comparatively less damaged, accumulated high amounts of fat. In severe cases, the enzymatic and cytoskeletal lesions were accompanied by hematuria and tubular necroses including and collecting ducts in the renal papilla. In less severe cases reduced activities of brush border hydrolases were the only sign of disturbed renal function in maternal rats indicating that membrane alteration and loss of membrane-bound enzymes are the primary defects. In the fetal kidneys, mitotic activity of the cells of the nephron anlagen and collecting ducts was reduced and enzymatic and morphological differentiation were disturbed. As a consequence less mature nephrons and collecting ducts occurred.
Gossrau
R
R
Department of Anatomy, Free University of Berlin, Germany.
Günther
T
T
Merker
H J
HJ
Graf
R
R
D000818:Animals; D002118:Calcium / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D005609:Free Radicals; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008854:Microscopy, Electron; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012459:Salicylates / Q000633:toxicity*; D020156:Salicylic Acid; D014746:Vimentin / Q000032:analysis; D015032:Zinc / Q000172:deficiency*
D005609:Free Radicals; D012459:Salicylates; D014746:Vimentin; D015032:Zinc; D020156:Salicylic Acid; D002118:Calcium