Summary
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 aecompanied by hematuria and tubular necroses including the 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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bettger WJ, O'Dell BL (1981) A critical physiological role of zine in the structure and function of biomembranes. Life Sci 28:1425–1438
Burke JP, Fenton MR (1985) Effect of a zinc-deficient diet on lipid peroxidation in liver and tumor subcellular membranes. Proc Soc Exp Biol Med 179:187–191
Chengelis CP, Dodd DC, Means JR, Kotsonis FN (1986) Protection by zinc against acetaminophen induced hepatoxicity in mice. Find Appl Toxicol 6:278–284
Cicurel L, Schmid B (1986) In vitro teratogeneity of acetyl salicylic acid on rat embryos: Studies with various culture conditions. Methods Find Exp Clin Pharmacol 8:227–232
Farber JL (1981) The role of calcium in cell death. Life Sci 29:1289–1295
Fridovich I (1974) Superoxide dismutases. Adv Enzymol 41:35–95
Geyer G (1973) Ultrahistochemie. Histochemische Arbeitsvorschriften für die Elektronenmikroskopie. 2 Aufl. Gustav Fischer, Stuttgart
Gossrau R (1981) Investigation of proteinases in the digestive tract using 4-methoxy-2-naphithylamine (MNA) substrates. J Histochem Cytochem 29:464–480
Gossrau R, Lojda Z, Ruhnke M (1987) Histochemical detection of α-d-glucosidases and their molecular forms with 5-Br-4-Cl-3-indoxyl-α-d-glucoside. Histochemistry 86:397–404
Graf E, Mahoney JR, Bryant RG, Eaton JW (1984) Iron-catalyzed hydroxyl radical formation. J Biol Chem 259:3620–3624
Günther T, Vormann J (1988) Perinatal development of superoxide dismutase in rat liver and kidney. In: Hurley LS (ed) Proceedings 6. international symposion on trace elements in man and animals (in press)
Günther T, Vormann J, Merker HJ, Averdunk R, Peter HW, Wonigeit K (1984) Membrane alterations in magnesium-deficiency-induced malignant T cell lymphoma. Magnesium 3:29–37
Günther T, Höllriegel V, Vormann J (1988) Effect of salicylate and zinc deficiency on the serum concentrations of magnesium, calcium and parathyroid hormone. Biol Trace Elem Res (in press)
Hackman R, Hurley LS (1984) Interactions of salicylate, dietary zinc, and genetic strain in teratogenesis in rats. Teratology 30:225–236
Halliwell B (1987) Free radicals and metal ions in health and disease. Proc Nutr Soc 46:13–26
Kimmel CA, Wilson JG, Schumacher HJ (1971) Studies on metabolism and identification of the causative agent in aspirin teratogenesis in rats. Teratology 4:15–24
Kleinknecht D, Landais P, Goldfarb B (1987) Pathophysiology and clinical aspects of drug-induced tubular necrosis in man. Contrib Nephrol 55:145–185
Kyle ME, Kocsis JJ (1985) The effect of age on salicylate-induced nephrotoxicity in male rats. Toxicol Appl Pharmacol 81:337–347
Kyle ME, Kocsis JJ (1986) Metabolism of salicylate by isolated kidney and liver mitochondria. Chem Biol Interact 59:325–335
Lemasters JJ, DiGuiseppi J, Nieminen AL, Herman B (1987) Blebbing, free Ca2+ and mitochondrial membrane potential preceding cell death in hepatocytes. Nature 325:78–81
Lojda Z, Gossrau R, Schiebler TH (1979) Enzyme histochemistry. A laboratory manual. Springer Berlin Heidelberg New York
Martens ME, Lee CP (1984) Reye's syndrome: Salicylates and mitochondrial functions. Biochem Pharmacol 33:2869–2876
Mühlenfeld WE (1969) Über die Entwicklung und Chemodifferen-zierung der Rattenniere unter besonderer Berücksichtigung der Geschlechtsunterschiede. Histochemie 18:97–131
Nicotera T, Hartzell P, Davis G, Orrenius S (1986) The formation of plasma membrane blebs in hepatocytes exposed to agents that increase cytosolic Ca2+ is mediated by the activation of a non-lysosomal proteolytic system. FEBS Lett 209:139–144
Prasad AS (1979) Clinical, biochemical and pharmacological role of zinc. Annu Rev Pharmacol Toxicol 20:393–426
Rogers JM, Keen KL, Hurley LS (1985) Zinc deficiency in pregnant Long-Evans hooded rats: Teratogeneity and tissue trace clements. Teratology 31:89–100
Romeis B (1968) Mikroskopische Technik. R Oldenbourg, München
Schweichel JV, Merker HJ (1973) The morphology of various types of cell death and prenatal tissues. Teratology 7:253–256
Slater TF, Cheeseman KH, Davies MJ, Proudfoot K, Xin W (1987) Free radical mechanisms in relation of tissue injury. Proc Nutr Soc 46:1–12
Thiel G (1986) Experimental cyclosporine A nephrotoxicity: A summary of the international workshop (Basle, April 24–26) Clin Nephrol (Suppl) 25:S205-S210
Thomas JP, Bachowski GJ, Girotti AW (1986) Inhibition of cell membrane lipid peroxidation by cadmium and zinc-metallothioneins. Biochim Biophys Acta 884:448–461
Vormann J, Günther T (1986) Development of fetal mineral and trace element metabolism in rats with normal as well as magnesium-and zinc-deficient diets. Biol Trace Elem Res 9:37–53
Vormann J, Höllriegl V, Merker HJ, Günther T (1986) Effect of salicylate on zinc metabolism in fetal and maternal rats fed normal and zinc-deficient diets. Biol Trace Elem Res 9:55–64
Wilson RL (1987) Vitamin, selenium, zinc and copper interactions in free radical protection against ill-placed iron. Proc Nutr Soc 46:27–34
Author information
Authors and Affiliations
Additional information
Dedicated to Professor Zdenek Lojda on the occasion of his 60th birthday
Supported by the German Research Foundation (Sfb 174)
Rights and permissions
About this article
Cite this article
Gossrau, R., Günther, T., Merker, H.J. et al. Enhancement of maternal and fetal nephrotoxicity of salicylate by zinc deficiency. Histochemistry 89, 81–90 (1988). https://doi.org/10.1007/BF00496589
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00496589