Top

Published in:

01-07-2003 | Original Article

Thyroxine prevents reoxygenation injury in isolated proximal tubule cells

Authors: Elif Erkan, Abdullah Sakarcan, Gonca Haklar, Suha Yalcin

Published in: Pediatric Nephrology | Issue 7/2003

Abstract

Ischemia is characterized by cessation of blood flow and oxygen delivery to tissues that results in disruption of cellular structure and organelles. However, restoration of blood flow following ischemia causes reperfusion injury, characterized by further damage in the tissues mediated by reactive oxygen species. In the kidney, reactive oxygen molecules have been implicated in ischemic, toxic and immunological glomerular damage. Thyroxine has been shown to be cytoprotective in toxic and ischemic injury. Thyroxine's cytoprotective effect is postulated to be secondary to stimulation of intracellular ATP synthesis. However, the underlying mechanism of that beneficial effect remains to be investigated. In this study we investigated the effect of thyroxine (T4) on free oxygen radical production in an in vitro model of reperfusion injury. Free oxygen radical (FOR) levels were determined by a chemiluminescence method after freshly isolated rabbit proximal tubule cells were subjected to 15 min of anoxia followed by 45 min of reoxygenation. Reoxygenation injury resulted in a significant increase in FOR levels (P<0.0001). FOR levels were significantly lower in the group treated with thyroxine (P=0.01) and cells treated with thyroxine displayed better preservation of cellular structure. We conclude that thyroxine's cytoprotective effect might be via decreased synthesis of FOR, and thyroxine treatment may confer cytoprotection in renal conditions characterized by FOR-mediated injury.

Zimmerman BJ, Granger ON (1992) Reperfusion injury. Surg Clin North Am 72:65–83PubMed

McCord JM (1985) Oxygen-derived free radicals in postischemic tissue injury. N Eng J Med 312:159–163

Grace PA (1994) Ischemia-reperfusion injury. Br J Surg 81:637–647PubMed

Rovin BH, Wurst E, Kohan DE (1990) Production of reactive oxygen species by tubular epithelial cells in culture. Kidney Int 37:1509–1514PubMed

Shah SV (1989) Role of reactive oxygen metabolites in experimental glomerular disease. Kidney Int 35:1093–1106PubMed

Diamond JR, Bonventre N, Karnovsky MJ (1986) A role for oxygen free radicals in aminonucleoside nephrosis. Kidney Int 29:478–483PubMed

Zager RA (1992) Gentamicin effects on renal ischemia/reperfusion Injury. Circ Res 70:20–28PubMed

Walker PD, Shah SV (1988) Evidence suggesting a role for hydroxyl radical in gentamicin-induced acute renal failure in rats. J Clin Invest 81:334–341PubMed

Baud L, Ardaillou R (1993) Involvement of reactive oxygen species in kidney damage. Br Med Bull 49:621–629PubMed

10.

Paller MS, Hoidal JR, Ferris T (1984) Oxygen free radicals in ischemic acute renal failure in the rat. J Clin Invest 74:1156–1164PubMed

11.

Hansson R, Jonsson O, Lundstam S, Petterson S, Schersten T, Waldenstrom J (1983) Effects of free radical scavengers on renal circulation after ischemia in the rabbit. Clin Sci 65:605–610PubMed

12.

Mangino MJ, Murphy MK, Grabau GG, Anderson CB (1991) Protective effects of glycine during hypothermic renal ischemia-reperfusion injury. Am J Physiol 261:F84l–848

13.

Bratell S, Haraldsson G, Herlitz H, Jonsson O, Pettersson S, Schersten T, Waldenstrom J (1990) Protective effects of pretreatment with superoxide dismutase, catalase and oxypurinol on tubular damage caused by transient ischaemia. Acta Physiol Scand 139:417–425PubMed

14.

Haraldsson G, Sorensen V, Nilsson U, Pettersson S, Rashid M, Schersten T, Akerlund S, Jonsson O (1995) Effect of pre-treatment with desferrioxamine and mannitol on radical production and kidney function after ischaemia-reperfusion. A study on rabbit kidneys. Acta Physiol Scand 154:461–468PubMed

15.

Baker GL, Corry RJ, Autor AP (1985) Oxygen free radical induced damage in kidneys subjected to warm ischemia and reperfusion. Protective effect of superoxide dismutase. Ann Surg 202:628–640PubMed

16.

Venkatachalam MA, Bernard DB, Donohoe JF, Levinsky NG (1978) Ischemic damage and repair in the rat proximal tubule. Differences among the SI, S2 and S3 segments. Kidney Int 14:31–49

17.

Paller MS, Neumann TV (1991) Reactive oxygen species and rat renal epithelial cells during hypoxia and reoxygenation. Kidney Int 40:1041–1049PubMed

18.

Andreoli SP, McAteer JA (1990) Reactive oxygen molecule-mediated injury in endothelial and renal epithelial cells in vitro. Kidney Int 38:785–794PubMed

19.

Southard JH, van Gulich TM, Ametani MS, Vreugdenhil PK, Lindell SL, Pienaar BL, Belzer FO (1991) Important components of the UW solution. Transplantation 49:251

20.

Okusa MD (2002) The inflammatory cascade in acute ischemic renal failure. Nephron 90:133–138CrossRefPubMed

21.

Deng J, Kohda Y, Chiao H, Wang Y, Hu X, Hewitt SM, Miyaji T, McLeroy P, Nibhanupudy B, Li S, Star RA (2001) Interleukin-l0 inhibits ischemic and cisplatin-induced acute renal injury. Kidney Int 60:2118–2128CrossRefPubMed

22.

Chatterjee PK, Patel NS, Kvale EO, Cuzzocrea S, Brown PA, Stewart KN, Mota-Filipe H, Thiemermann C (2002) Inhibition of inducible nitric oxide synthase reduces renal ischemia/reperfusion injury. Kidney Int 61:862–871CrossRefPubMed

23.

Fernandez V, Videla LA (1993) Influence of hyperthyroidism on superoxide radical and hydrogen peroxide production by rat liver submitochondrial particles. Free Radic Res Commun 18:329–335PubMed

24.

Capasso G, De Tommaso G, Pica A, Anastasion P, Capasso J, Kinne R, De Santo NG (1999) Effects of thyroid hormones on heart and kidney functions. Miner Electrol Metab 25:56–64CrossRef

25.

Sutter PM, Thulin G, Stromski M, Ardito T, Gaudio KM, Kashgarian M, Siegel NJ (1988) Beneficial effect of thyroxin in the treatment of ischemic acute renal failure. Pediatr Nephrol 2:1–7PubMed

26.

Schulte-Wissermann H, Straub E, Funke PL (1977) Influence of l-thyroxine upon enzymatic activity in the renal epithelium of the rat under normal conditions and in mercury-induced lesions. I. Histochemical studies of alkaline phosphatase, acid phosphatase, adenosine-tri-phosphatase and leucine-aminopeptidase. Virchows Arch B Cell Pathol 23:163–173PubMed

27.

Cronin RE, Brown DM, Simonsen R (1986) Protection by thyroxine in nephrotoxic acute renal failure. Am J Physiol 251:F408–412PubMed

28.

Sakarcan A, Timmons C, Baum M (1994) Intracellular distribution of cystine in cystine-loaded proximal tubules. Pediatr Res 35:447–450PubMed

29.

Weinberg JM, Davis JA, Abarzua M, Rajan T (1987) Cytoprotective effects of glycine and glutathione against hypoxic injury to renal tubules. J Clin Invest 80:1446–1454PubMed

30.

Lowry OH, Rosebrough NJ, Farr L (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

31.

Van Dyke K, Van Scott MR, Castranova V (1986) Measurement of phagocytosis and cell-mediated cytotoxicity by chemiluminescence. Methods Enzymol 132:498–507PubMed

32.

Rhoden E, Pereira-Lima L, Lucas M, Mauri M, Rhoden C, Pereira-Lima JC, Zettler C, Petteffi L, Bello-Klein A (2000) The effects of allopurinol in hepatic ischemia and reperfusion: experimental study in rats. Eur Surg Res 32:215–222CrossRefPubMed

33.

Yokoyama K, Nakamura K, Saita Y, Itoman M (2000) Time course of superoxide anion radicals generation in two ischemia-reperfusion models; comparison between hindlimb replant model and isolated rectus femoris muscle model. Br J Plast Surg 53:516–519CrossRefPubMed

34.

Gaudio KM, Thulin G, Ardito T, Kashgarian M, Siegel NJ (1989) Metabolic alterations in proximal tubule suspensions obtained from ischemic kidneys. Am J Physiol 257:F383–389PubMed

35.

Weinberg JM (1985) Oxygen deprivation-induced injury to isolated rabbit kidney tubules. J Clin Invest 76:1193–1208PubMed

36.

Takano T, Soltoff S, Murdaugh S, Mandel LJ (1985) Intracellular respiratory dysfunction and cell injury in short-term anoxia of rabbit renal proximal tubules. J Clin Invest 76:2377–2384PubMed

37.

Saugstad OD (1996) Role of xanthine oxidase and its inhibitor in hypoxia: reoxygenation injury. Pediatrics 98:103–107PubMed

38.

Doctor RB, Mandel LJ (1991) Minimal role of xanthine oxidase and oxygen free radicals in rat renal tubular reoxygenation injury. J Am Soc Nephrol 1:959–969PubMed

39.

Linas SL, Whittenburg D, Repine J (1990) Role of xanthine oxidase in ischemia/reperfusion injury. Am J Physiol 258:F711–716PubMed

40.

Joannidis M, Gstraunthaler G, Pfaller W (1990) Xanthine oxidase: evidence against a causative role in renal reperfusion injury. Am J Physiol 27:F232–236

41.

Siegel NJ, Gaudio KM, Katz LA, Reilly HF, Ardito TA, Hendler FG, Kashgarian M (1984) Beneficial effect of thyroxine on recovery from toxic acute renal failure. Kidney Int 25:906–911PubMed

42.

Boydstun I, Thulin G, Siegel NJ (1992) Mechanism of post-ischemic augmentation of renal ATP by thyroxine (abstract). Pediatr Res 31:329A

43.

Boydstun I, Najjar S, Kashgarian M, Carpenter T, Siegel N (1995) Post-ischemic thyroxine stimulates renal mitochondrial adenine nucleotide translocator activity. Am J Physiol 268:F651–656

44.

Espinosa RE, Keller MJ, Yusufi NK, Dousa TP (1984) Effect of thyroxine administration on phosphate transport across renal cortical brush border membrane. Am J Physiol 246:F133–139PubMed

45.

Bonventre N (1993) Mechanisms of ischemic acute renal failure. Kidney Int 43:1160–1178

46.

Wijkhuisen A, Djouadi F, Vilar J, Merlet-Benichou C, Bastin J (1995) Thyroid hormones regulate development of energy metabolism enzymes in rat proximal convoluted tubule. Am J Physiol 268:F634–642PubMed

47.

Acker CG, Singh AR, Flick RP, Bernardini J, Greenberg A, Johnson JP (2000) A trial of thyroxine in acute renal failure. Kidney Int 57:293–298CrossRefPubMed

48.

Bald M, Hauffa BP, Wingen AM (2000) Hypothyroidism mimicking chronic renal failure in reflux nephropathy. Arch Dis Child 83:251–252CrossRefPubMed

Title: Thyroxine prevents reoxygenation injury in isolated proximal tubule cells
Authors: Elif Erkan
Abdullah Sakarcan
Gonca Haklar
Suha Yalcin
Publication date: 01-07-2003
Publisher: Springer-Verlag
Published in: Pediatric Nephrology / Issue 7/2003
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-003-1123-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Thyroxine prevents reoxygenation injury in isolated proximal tubule cells

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 7/2003

Neonatal nephrocalcinosis in association with glucose-galactose malabsorption

Gitelman syndrome: when will it turn into Gitelman disease?

Progression of chronic renal failure in focal segmental glomerulosclerosis: consequence of podocyte damage or of tubulointerstitial fibrosis?

Acute leukemia: an association with atypical hemolytic uremic syndrome

A de novo R589C mutation of anion exchanger 1 causing distal renal tubular acidosis

Nephrocalcinosis and medullary cysts in 3-methylglutaconic aciduria