Myocardial necrosis due to vitamin D3 overdose - scanning electron microscopic observations

• Autorzy: Walentynowicz O , Kubasik-Juraniec J. , Rudzinska-Kisiel T.
• Języki publikacji: EN

Abstrakty

EN

Our studies were carried out on the hearts of virgin female Wistar rats treated with 100.000 i.u. of vitamin D₃ (calciol) per os for 3 consecutive days. Multifocal cardionecrosis was established macroscopically in 70% of the vitamin D-treated rats on the 7th day of the experiment when the rats were in the acute phase of intoxication. Using a scanning electron microscopy (SEM), we received three-dimensional information about the structural changes to the rat myocardium damaged by high doses of vitamin D₃. The images of necrotic hearts revealed significant disruption of the structural integrity of the myocardium linked to fragmentation of the cardiac muscle bundles and a visible disruption of the extracellular matrix (ECM) components. In healthy hearts, the structural integrity of the myocardium and the dense network of the extracellular matrix were well preserved. In parallel, the effect of an increasing concentration of free Ca²⁺ on the total proteolytic activity of the heart muscle homogenate of the healthy and necrotic rats was investigated at neutral pH. These data showed that following vitamin D₃ intoxication, the proteolytic processes in the rat hearts occurred in Ca²⁺ overload or saturation. On the basis of our morphological and biochemical results we can suggest that calcium-activated neutral proteinases may have contributed to the structural alteration of the extracellular matrix components and were in this way involved in vitamin D-induced cardionecrosis.

Słowa kluczowe

EN

calciol; cardiac myocyte; vitamin D3; toxicity; calpain; extracellular matrix; scanning electron microscopy; myocardial necrosis

• Wydawca: -
• Czasopismo: Folia Morphologica
• Rocznik: 2004
• Tom: 63
• Numer: 4
• Opis fizyczny: p.439-444,fig.,ref.

Twórcy

autor

Walentynowicz O

• Medical University, Debinki 1, 80-210 Gdansk, Poland

autor

Kubasik-Juraniec J.

autor

Rudzinska-Kisiel T.

Bibliografia

• 1. Adachi E, Makaiyama T, Sasai K, Hayashi T, Kawashima S, Kasai Y, Hayashi M, Hashimoto PH (1990) Immunohistochemical evidence of the extracellular localization of calcium-activated neutral protease (CANP) in rabbit skeletal muscle, lung and aorta. Arch Histol Cytol, 53: 413–422.
• 2. Artur GD, Belcastro AN (1997) A calcium stimulated cysteine protease involved in isoproterenol induced cardiac hypertrophy. Mol Cell Biochem, 176: 241–248.
• 3. Bajusz E (1963) Conditioning factors for cardiac necroses. Karger, Basel.
• 4. Caulfield JB, Wolkowicz PE (1990) Myocardial connective tissue alterations. Toxicologic Pathology, 18: 488–496.
• 5. Dormanen MC, Bishop JE, Hammond MW, Okamura WH, Nemere I, Norman AW (1994) Nonnuclear effect of steroid hormone 1a,25(OH)2-vitamin D3: Analogs are able to functionally differentiate between nuclear and membrane receptors. Biochem Biophys Res Commun, 201: 394–401.
• 6. Elamrani N, Balcerzak D, Soriano M, Brustis JJ, Cottin P, Poussard S, Ducastaing A (1993) Evidence for fibronectin degradation by calpain II. Biochimie, 75: 849–853.
• 7. Gornall AG, Bardawill CJ, David MM (1949) Determination of serum proteins by means of the biuret reaction. J Biol Chem, 177: 751–766.
• 8. Iizuka K, Kawaguchi H, Yasuda H, Kitabatake A (1992) The role of calcium activated neutral protease on myocardial cell injury in hypoxia. Jpn Heart J, 33: 707–715.
• 9. Kar NC, Pearson CM (1976) A calcium-activated neutral protease in normal and dystrophic human muscle. Clin Chim Acta, 73: 293–297.
• 10. Kunimatsu M, Tada T, Narita Y, Ozaki Y, Liu ZQ, Shearer TR, Sasaki M (1999) Activation of calpain in myocardial infarction: an immunohistochemical study using a calpain antibody raised against active site histidine-containing peptide. Cardiovasc Pathol, 8: 7–15.
• 11. Mathiasen IS, Sergeev IN, Bastholm L, Elling F, Norman AW, Jaattela M (2002) Calcium and calpain as key mediators of apoptosis-like death induced by vitamin D compounds in breast cancer cells. J Biol Chem, 277: 30738–30745.
• 12. Morita T, Awakura T, Shimada A, Umemura T, Nagai T, Haruna A (1995) Vitamin D toxicosis in cats: natural outbreak and experimental study. J Vet Med Sci, 57: 831–837.
• 13. Nirmala C, Puvanakrishnan R (1998) Collagen profile in isoproterenol induced myocardial necrosis in rats. Indian J Exp Biol, 36: 763–767.
• 14. Norman AW, Collins ED (1996) Vitamin D receptor structure, expression, and nongenomic effects. Principles of Bone Biology. Academic Press, San Diego, CA. Chapter 30: 419–434.
• 15. Robinson TF, Cohen-Gould L, Factor SM, Eghbali M, Blumenfeld OO (1988) Structure and function of connective tissue in cardiac muscle: collagen types I and III in endomysial struts and pericellular fibers. Scanning Microsc, 2: 1005–1015.
• 16. Robinson TF, Cohen-Gould L, Remily RM, Capasso JM, Factor SM (1985) Extracellular structures in heart muscle. Adv Myocardiol, 5: 243–255.
• 17. Suzuki K, Shimizu K, Hamamoto T, Nakagawa Y, Murachi T, Yamamuro T (1992) Characterization of proteoglycan degradation by calpain. Biochem J, 285: 857–862.
• 18. Świerczyński J, Nagel G, Żydowo MM (1987) Calcium content in some organs of rats treated with toxic calciol dose. Pharmacology, 34: 57–60.
• 19. Walentynowicz O, Wrzołkowa T (1995) Pathogenesis of heart myofibril lesion in experimental vitamin D-induced cardionecrosis. Exp Mol Pathol, 63: 200–209.
• 20. Wrzołek MA (1985) The effect of zinc on vitamin D3-induced cardiac necrosis. J Mol Cell Cardiol, 17: 109–117.
• 21. Wrzołkowa T, Żydowo MM (1980) Ultrastructural studies on the vitamin D induced heart lesion in the rat. J Mol Cell Cardiol, 12: 1117–1133.
• 22. Wrzołkowa T, Rudzińska-Kisiel T, Kłosowska B (1991) Calcium content of serum and myocardium in vitamin D-induced cardionecrosis. Bone Miner, 13: 111–121.
• 23. Takahashi S, Barry AC, Factor SM (1990). Collagen degradation in ischaemic rat hearts. Biochem J, 265: 233–241.
• 24. Toyo-oka T, Morita M, Shin WS, Okaimotsuo Y, Sugimoto T (1991) Contribution of calcium-activated neutral protease to the degradation process of ischemic heart. Jpn Circ, 55: 1124–1126.
• 25. Tyagi SC (1997) Proteinases and myocardial extracellular matrix turnover. Mol Cell Biochem, 168: 1–12.