References

nid

Нефрология и диализ

Nephrology and Dialysis

1680-44222618-9801

Российское диализное общество

nid-3780

Research Article

ОБЗОРЫ И ЛЕКЦИИ

REVIEWS AND LECTURES

Тяжелые металлы: механизмы нефротоксичности (Обзор литературы)

Toxic Metals: Mechanisms Of Nefrotoxicity

Аксенова

М. Е.

Aksionova

M. E.

noemail@neicon.ru

НИИ Педиатрии и детской хирургии МЗ РФ, МоскваRussian Federation

2000

28062025

21-23943

2025

Аксенова М.Е.

Aksionova M.E.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://journal.nephro.ru/jour/article/view/3780

Почки являются органом-мишенью для действия ксенобиотиков, особенно тяжелых металлов. Цитотоксичность металлов обусловлена тремя взаимосвязанными механизмами: усилением перекисного окисления липидов; угнетением митохондриального дыхания; нарушением кальциевого гомеостаза клетки. Знание патогенетических механизмов цитотоксического действия тяжелых металлов позволяет обосновать использование в профилактике и терапии заболеваний, связанных с хроническим действием ксенобиотиков, антиоксидантов, мембраностабилизаторов, препаратов, улучшающих функцию митохондрий и блокаторов кальциевых каналов.

Kidney is the «target» organ for xenobiotics especially for toxic metals. Citotoxicity of these metals is caused by three interacting mechanisms: intensification of lipids peroxidation; depression of oxidative phosphorylation in mitochondrias; pathology of calcium homeostasis. Correspondingly, therapy with antioxidants, membrane stabilisers, drugs affecting function of mitochondrias and blocators of calcium channels should be included in prophylactics and pathogenetic therapy of chronic xenobiotic poisoning.

тяжелые металлынефротоксичностьперекисное окисление липидовмитохондриикальций

References1

Вельтищев Ю.Е. Концепция риска болезни и безопасности здоровья ребенка. Росс.вест.перинат.и педиат., прилож. к журнал., лекц.2: 20.

Вельтищев Ю.Е., Фокеева В.В. Экология и здоровье детей. Химическая экопатология. Росс.вест.перинат. и педиат.,прилож.к журналу., лекц.9: 23-27.

Длин В.В., Османов И.М., Юрьева Э.А. Терапия нефропатий, развивающихся под влиянием неблагоприятных антропогенных экологических воздействий(соли тяжелых металлов) I конгресс пед.-нефрол. России, 17-19 сент.1996; С.-П.,тез.докл.,47-51.

Лисицин Ю.П. Слово о здоровье. М.,1986; 283.

Османов И.М. Клинико-патогенетические особенности и тактика лечения поражений почек у детей в экологически неблагополучных регионах Автореф. дисс.соиск.уч.зв.докт.мед.наук.,М., 1996; 25-26.

Сумакова И.А. Некоторые патогенетические аспекты экопатологии почек у детей Дисс.соиск.зв.канд.мед.наук,М., 1996; 133-137.

Трухина О.Н. Характеристика нефропатий у детей в экологически неблагоприятном регионе по тяжелым металлам и обоснование использования мембранотропных препаратов для лечения этих больных Дисс.соиск.зв.канд.мед.наук,М.,1995; 103-130.

Aiyar J., Bercovits H.J., Floyd R.A. et al. Reaction of chromium with glutatione or with hydrogen peroxide: identification of reactive intermediates and their role in chromium-induced DNA-damage Env.Health Perspect., 1991; vol.92; 53-62.

Albano E., Bellomo G., Benedetti A. Alterations of hepatocyte Ca2+homeostasis by triethylated lead: are they correlated with cytotoxicity? Chem.Biolog.Interact., 1994; 90(1): 59-72.

Alia And, Saradhi P.P. Suppression in mitochondrial electron transport is the prime cause behind stress induced proline accumulation Biochem.Biophys.Res.Comm., 1993; 193(1): 54-58.

Ambrosi l., Lomonte C., Soleo L. et al. Nephropathy induced by heavy metals. Proceedings of the 4th Bari Seminar in Nephrology, Bari,Italy, apr.1990; 85-100

Andreoli S.P. Reactive oxygen molecules, oxydant injury and renal disease. Ped.Nephrol., 1991; 5: 733-742.

Angle C.R., Thomas D.J., Swanson S.A. Osteotoxicity of cadmium and lead in HOS TE 85 and ROS 17/28 cells: relation to metallothionein induction and mitochondrial binding. Biometalls, 1993; 6(3): 179-84.

Chavez E., Briones R., Michel B. Evidence for involvement of dithyol groups in mitochondrial calcium transport: studies with cadmium. Arch.Biochem.Biophys., 1985; 242: 493-497.

Cifone M.G., Alesse E., Procopio A. Effect of cadmium on lymphocyte activation. Biochem.Biophys.Acta,1989; 1011(1): 25-32.

Coban T., Beduke Y., Iscan M. In vitro effect of cadmium and nickel on glutation, lipid peroxidation and glutation-S-transferase in human kidneys. Toxicol. in vitro, 1996; 10: 241-245.

Dhawan M., Kachru D.N., Tandon S.K. Influence of thiamin and ascorbic acid supplementation on the antidotal efficacy of thiol chelators in experimental lead intoxication/ Arch.Toxicol., 1988; 62(4): 301-304.

Fowler B.A. Mechanisms of kidney cell injury from metals. Envir.Health Persp. 1992; 100: 56-63.

Franchini I., Mutti A. Tubulointerstitial nephropaties by industrial chemicals. Proceedings of the 4th Bari seminar in Nephrology, Bary, 1990; 119-127.

Fukino H., Hirai M., Hsuesh Y. Effect of the zinc pretreatment on mercury induced lipid peroxidation in the rat kidneys. Toxicol.Appl.Pharmacol., 1984; 73: 395-401.

Gonick H.C. Nephropathies of heavy metal intoxication. Testbook of nephrology., ed.Shaul, 1983; vol.I; 6: 184-6.194.

Goyer A. Environmentally related diseases of the urinary tract. Med.Clinics of Nord America; 1990; 74; 2: 377-389.

Gstraunthaler G., Pfaller W., Kotanko P. Glutation depletion and in vitro lipid peroxidation in mercury or maleate-induced acute renal failure. Biochem.Pharmacol., 1983; 32: 2969-72.

Halliwell B., Caroll E.C. Oxygen-derived species:the relation to human disease and environmental stress. Envir. Health. Perspect., 1994; 102; suppl.10: 5-12.

Harman A.W., Maxwell M.J. An evalution of the role of calcium in cell injury. Ann.Rev.Pharmacol.Toxicol.,1995; 35; 129-144.

Inesi G. Mechanism of calcium transport. A. Rev. Physiol.,1985; 47; 573-601.

Inglis I.A., Henderson D.A., Emmerson B.T. The pathology and pathogenesis of chronic lead nephropaty occurring in Queensland. J.Pathol.1978; 124; 65-73.

Kesseler A., Brand M.D. Localisation of the sites of action of cadmium on oxydative phosphorilation in potato tuber mitochondria using top-down elasticity analisis. Eur.J.Biochem., 1994; 225; 897-906.

Lauwerys R., Bernard A. Preclinical detection of nephrotoxicity: description of the test and appraisal of their health significance. Toxicol.Lett. 1989; 46; 13-29.

Legare M.E., Barhomi R., Burghardt R.S. Low-level lead exposure in cultured astroglia: identification of cellular targets with vital fluorescent process. Neurotoxicol.,1993; 14(2-3); 267-72.

Lockitch G. Perspectives on lead toxicity. Clin.Biochem., 1993; vol.26; 371-381.

Louwerys R.R., Bernard A.M., Roels H.A. al. Cadmium: exposure markers as predictors of nephrotoxic effects. Clin.Chem.1994; 40(7 Pt2);1391-4.

Lund B.O., Miller D.M. Studies in Hg-induced H2O2 production and lipid peroxidation in vitro in rat kidney mitochondria. Biochem.Pharmacol., 1993; 45; 2017-24.

Malis C.D., Bonventre J. Susceptibility of mitochondrial membrans to calcium and reactive oxygen species: implication for ishemic and toxic tissue damage. Pros.Clin.Biol.Res., 1988; 282; 235-259.

Martel J., Marion M., Denizenu F. Effect of cadmium on membrane potential in isolated rat hepatocytes. Toxicol., 1990; 60; 161-172.

Mateo M.C., Aragon P., Prieto M.P. Inhibitory effect of cysteine and methionine on free radicals induced by mercury in red blood cells of patients undergoing haemodialysis. Toxicol.in vitro, 1994; 8; 4; 597.

Minnema D.G., Michelson I.A., Cooper G.P. Calcium efflux and neurotransmitter release from rat hippocampal synaptosomes exposed to lead. Toxicol.Appl.Pharmacol., 1988; 92; 351-357.

Nagyova A., Galbavy S., Ginter E. Histopatological evidance of vitamin C protection against Cd-nephrotocity in guinea pigs. Exp. Toxicol. Pathol., 1994; 46(1): 11-14.

Orrenius S., McCoukey D.J., Bellomo G. Role of Ca2+ in toxic cell killing. Trends Pharmacol.Sci., 1989; 10; 281-285.

Passada R. Effect of intraperitoneal cadmium administration on mitochondrial enzymes in rat tissue. Toxicol., 1983; 27; 81.

Petering D.H., Fowler B.A. Metabolism of cadmium, zinc and copper in the rat kidney: the role of metallothionein and other binding sites. Env.Health.Perspect., 1986; 65; 217-224.

Pounds J.G., Long G.J., Rosen J.F. Cellular and molecular toxicity of lead in bone. Environ.Health.Perspect., 1991; 91; 17-32.

Rosenberg D.W., Kappas A. Induction of heme oxygenase in the small intestinal epitelium: a response to oral cadmium exposure. Toxicol., 1991; 67(2); 199-210.

Rossi E., Costin K.A. Effect of occupational lead exposure on lymphocyt enzymes involved in hemo biosynthesis. Clin.Chem.,1990; 36: 1980-3.

Sarkar S., Bhatnagar D., Poonam Y. Cadmium-induced lipid peroxidation in rat livers slice: a possible involvement of hydroxyl radicals. Toxicol.in vitro, 1994; 8,6: 1239-1242.

Schaich K.M. Metals and lipid oxidation. Contemporary issues. Lipids, 1992; 27(3): 209-18.

ShencherB.J., Rooney C., Vitale L. Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes: suppression of T-cell activation. Immunopharmacol. Immunotoxicol., 1992; 14(3): 539-553.

Uribe A., Chavez E., Jiemenez M. Characterization of Ca2+ transport in Euglena gracilis mitochondria. Biochemis. Biophys. Acta, 1994; 28; 1186(1-2): 107-116.

Viarengo A., Nicotera P. Possible role of Ca2+ in heavy metals cytotoxicity. Comp.Biochem.Physiol., 1991; 100C(1/2): 81-84.

Zagger R. Mitochondrial free radical production induced lipid peroxidation during myohemoglobinuria. Kidney Intern., 1996; 49: 741-51.

Zaman K., Maccil R.S., Johnson J.S. An insect for assessing mercury toxicity effect of mercury on antioxidant enzyme activities- housefly. Arch.Contam.Toxicol.,1994; 26: 114-118.

Zhang Y., Marcillat O., Giulivi C. The oxidative inactivation of mitochondrial electron transport chain components and ATPase. J.Biolog.Chemistry, 1990; 265; 27: 16330-36.

The authors declare that there are no conflicts of interest present.