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001-es BibID:	BIBFORM046615
Első szerző:	Agarwal, Anupam
Cím:	Induction of heme oxygenase in toxic renal injury : a protective role in cisplatin nephrotoxicity in the rat / Anupam Agarwal, József Balla, Jawed Alam, Anthony J. Croatt, Karl A. Nath
Dátum:	1995
ISSN:	0085-2538
Megjegyzések:	Cellular content of heme is regulated by heme oxygenase, the rate limiting enzyme in the degradation of heme. Induction of heme oxygenase is a protective response in an in vivo model of heme protein mediated renal injury, the glycerol model of acute renal failure. In addition to heme, heme oxygenase is induced by diverse forms of oxidative stress, the functional significance of which is currently unknown. We examined whether heme oxygenase is induced, and the functional significance of such induction, in two in vivo models of oxidant-induced toxic nephropathy, namely, cisplatin and gentamicin nephropathies; nephrotoxicity in these models is not dependent on the delivery of a burden of heme proteins to the kidney as occurs in the glycerol model. We demonstrate induction of heme oxygenase mRNA and protein in the kidney as early as 6 and 12 hours after a single dose of cisplatin (6 mg/kg i.v.). Pretreatment with tin protoporphyrin, a competitive inhibitor of heme oxygenase, led to higher serum creatinine values on days 3 through 5 and lower inulin clearances on day 5; tin protoporphyrin also exacerbated renal injury in this model. Renal hemodynamics studied at day 2 after cisplatin demonstrate reduced renal blood flow rates, increased renal vascular resistance and increased fractional excretion of sodium in rats treated with tin protoporphyrin. Tin protoporphyrin alone had no significant effect on serum creatinine and renal hemodynamics in rats with intact, disease-free kidneys. We confirmed that tin protoporphyrin prevented the increase in heme oxygenase activity induced by cisplatin. Induction of heme oxygenase by cisplatin was associated with increased kidney heme content and ferritin content.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Kidney International. - 48 : 4 (1995), p. 1298-1307. -
További szerzők:	Balla József (1959-) (belgyógyász, nephrológus) Alam, Jawed Croatt, Anthony J. Nath, Karl
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001-es BibID:	BIBFORM040627
Első szerző:	Agarwal, Anupam
Cím:	Renal tubular epithelial cells mimic endothelial cells upon exposure to oxidized LDL / Agarwal A., Balla J., Balla G., Croatt A. J., Vercellotti G. M., Nath K.
Dátum:	1996
ISSN:	0002-9513
Megjegyzések:	In protein-uric states, renal tubular epithelial cells are exposed to diverse macromolecules, including low-density lipoproteins (LDL), normally excluded from the urinary space. Oxidized LDL (LDLox) is incriminated in atherogenesis and glomerulosclerosis. Since urine is prooxidant, we considered whether LDLox injuries renal tubular epithelial cells (LLC-PK1). We demonstrate that the cytotoxicity of LDLox on LLC-PK1 cells resembles its toxicity to human umbilical vein endothelial cells (HUVEC) in that oxidized but not native LDL is injurious. Pretreatment of LLC-PK1 cells and HUVEC with antioxidants markedly reduced the cytotoxicity of LDLox. Pretreatment of LDL with antioxidants, prior to oxidation of LDL, vitiated its cytotoxicity. That LDLox is prooxidant was supported by expression of heme oxygenase, a redox-sensitive enzyme. LDLox induced heme oxygenase mRNA and enzyme activity. Pretreatment of LDL with antioxidants prior to oxidation attenuated heme oxygenase mRNA induction in LLC-PK1 and HUVEC. An iron chelator prevented cytotoxicity and heme oxygenase expression induced by LDLox. Based on these effects of LDLox, we draw an analogy between tubulointerstitial disease and atherogenesis and speculate that LDLox contributes to tubulointerstitial disease in proteinuric states.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	American Journal Of Physiology. - 271 : 4 Pt2 (1996), p. F814-F823. -
További szerzők:	Balla József (1959-) (belgyógyász, nephrológus) Balla György (1953-) (csecsemő és gyermekgyógyász, neonatológus) Croatt, Anthony J. Vercellotti, Gregory M. Nath, Karl
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001-es BibID:	BIBFORM040446
035-os BibID:	PMID:7723246
Első szerző:	Nath, Karl
Cím:	Heme protein-mediated renal injury : a protective role for 21-aminosteroids in vitro and in vivo / Karl A. Nath, József Balla, Anthony J. Croatt, Gregory M. Vercellotti
Dátum:	1995
ISSN:	0085-2538
Megjegyzések:	21-aminosteroids ("lazaroids") have recently excited much interest by virtue of their ability to inhibit lipid peroxidation in vitro and to protect against neural injury in vivo. We tested the effect of these compounds in models of heme protein-mediated renal injury in vitro and in vivo. We devised an in vitro model of heme protein-induced toxicity in which renal epithelial cells were exposed to heme proteins for one hour, after which they were subjected to glutathione depletion by 1-chloro-2,4-dinitrobenzene (CDNB). This model was associated with more than a threefold increase in lipid peroxidation (as measured by thiobarbituric acid reactive substances, TBARS) and a marked reduction in cellular glutathione content. In this model, 21-aminosteroids virtually prevented cytotoxicity as measured by the 51-chromium release assay, and significantly reduced TBARS in a dose-dependent manner. Catalase was partially protective in this model, thereby indicating hydrogen peroxide-dependent toxicity. While pursuing mechanisms accounting for enhanced cellular generation of hydrogen peroxide, we uncovered the first direct evidence that the heme prosthetic group per se directly stimulates cellular generation of hydrogen peroxide; complementing these findings is the remarkable efficacy of 21-aminosteroids in protecting against cytotoxicity induced by hydrogen peroxide. We also tested the capacity of 21-aminosteroids to protect against heme protein-mediated renal injury in vivo. Prior administration of 21-aminosteroids attenuated reductions in GFR and renal blood flow rates following the systemic infusion of methemoglobin in normal rats. 21-aminosteroids also attenuated renal injury observed over three successive days in the glycerol model of heme protein-mediated injury when this model was induced at a higher dose of glycerol (8 ml/kg body wt) but not at a lower dose (5 ml/kg body wt). We conclude that 21-aminosteroids protect against heme protein-mediated renal injury in vitro and in vivo. We suggest that these compounds are potentially useful in such clinical conditions as rhabdomyolysis, intravascular hemolysis and renal injury associated with hemoglobin-based red blood cell substitutes.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény
Megjelenés:	Kidney International 47 : 2 (1995), p. 592-602. -
További szerzők:	Balla József (1959-) (belgyógyász, nephrológus) Croatt, Anthony J. Vercellotti, Gregory M.
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