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Karaciğer ve böbrek üzerine etanolün toksisitesi ve L-NAME. in koruyucu etkisi

Year 2008, Volume: 15 Issue: 4, 11 - 17, 29.05.2009

Abstract

Süleyman Demirel Üniversitesi
TIP FAKÜLTESİ DERGİSİ: 2008 Aralık; 15 (4)

Karaciğer ve böbrek üzerine etanolün toksisitesi ve L-NAME. in koruyucu etkisi

Recep Kutlubay*, Emin Oğuzhan Oğuz*, Günfer Turgut**, Erdoğan Kocamaz*,


Özet
Amaç: Histolojik olarak etanolün belli dozda karaciğer ve böbrekte yarattığı hasar ve bu hasarı önlemek üzere verilen L-NAME.in muhtemel koruyucu etkisinin gösterilmesi. Gereç ve yöntem: Çalışmada 6 aylık Wistar erkek sıçanlar kullanılmıştır. Sıçanlar rastgele 10.arlı 4 gruba ayrılmışlardır: I- Kontrol (n=10) II-Etanol (n=10) III- L-NAME (n=10) IV-Etanol+ L-NAME (n=10) L-NAME litrede 0.1 gram olacak şekilde, etanol ise hacmen %20 olacak şekilde yukarıda belirtilen gruptaki sıçanların içme sularına karıştırılarak 30
gün boyunca verilmiştir. Bulgu ve sonuçlar: Deney sonucu alınan kimysallara bağlı olarak herhangi bir hayvan ölümü gözlenmedi. Böbrek.te etanol grubunda Bowman boşluklarının daraldığı, tübül hücrelerinin yer yer belirgin vakuolleşmeler gösterdiği, tübül epiteline ait hücre çekirdeklerinin patolojik görüntüler sergilediği görüldü. Etanolle + L-NAME grubunda Bowman boşlularının kontrollerdekine benzer şekilde normal genişlikte olduğu, tübüllerin hemen hemen tamamına yakını normal olduğu görüldü. Sadece L-
NAME uygulanan gruptaki glomeruluslar ve tübüler yapılar kontrollerdekinden faklılık göstermedi Karaciğer.de Etanol grubunun genel görüntülerinde sinüzoidler belirgin şekilde daralmıştı. Hepatosit kordonları yer yer düzensiz hücre yığınları halinde olduğu, sinüzoidlerin büyük oranda ortadan kalktığı, belirlendi. Ayrıca bazı hepatositler dejeneratif görüntüler sergilemekteydi. Etanol + L-NAME grubunda sinüzoidler nomal görünümlüydü. Lobül periferinde çok küçük bir bölgede hafif düzensizlikler olmasına rağmen hepatosit kordonları normal görünümdeydi. Sadece L-NAME uygulanan grupta sinüzoidlerin, hepatosit kordonlarının ve hepatosit sitoplazmalarının kontrollerdekinden belirgin bir farklılık göstermediği belirlendi. Bu bulgulara göre karaciğer ve böbrek dokularında etanolün kendi başına yarattığı yapısal hasarın L-NAME ile birlikte verildiğinde büyük oran da azaldığı gözlendi.

Anahtar kelimeler: Etanol, L-NAME, karaciğer, böbrek, toksisite, ışık mikroskobu

Abstract

The toxic effect of etanol on liver and kidney and the protective effect of L-NAME
Aim: To show the histological liver and renal damage caused by ethanol at a certain dose and to show possible protective role of L-NAME. Materials and Methods: In this study, 40, 6 month-old Wistar rats were randomly divided into four groups: I- Control (n=10) II- Etanol (n=10) III-L-NAME (n=10) IV-Etanhol + L-NAME (n=10) 1g/lt L-NAME and 20% etanol were added into drinking water for 30 days. Results: At the end of the experiment, no animal died to due the given agents. In kidney, in ethanol group, narrowing in Bowman spaces, vacuolisation and pathologic appearance in tubule epithelium were observed. Ethanol +
L-NAME group showed normal Bowman spaces similar in control group and almost normal tubuli structure. Only L-NAME group showed normal appearance as it was in control group in terms of glomerular and tubular structures.In liver, in ethanol group there was significant narrowing in sinusoids, in some places irregular hepatocyte accumulations, degenrative

References

  • Sivapiriya V, Jayanthisakthisekaran, Venkatraman S. Effects of dimethoate (O,O-dimethyl S-methyl carbamoyl methyl phosphorodithioate) and Etanol in antioxidant status of liver and kidney of experimental mice. Pesticide Biochemistry and Physiology June 2006; 85(2): 115 -121.
  • Scott RB, Reddy KS, Husain K, Schlorff EC, Rybak LP, Somani SM. Dose response of etanol on antioxidant defense system of liver, lung, and kidney in rat. Pathophysiology 2000; 7: 25–32.
  • Majchrowicz E. Induction of physical dependance upon etanol and the associated behavioral changes in rats. Psychopharmachologia 1975; 43; 245–254.
  • Bondy SC, Etanol toxicity and oxidative stress. Toxicol. Lett. 1992; 63: 231–241.
  • Lankisch PG, and Banks PA. Pancreatitis New York, Berlin, Heidelberg: Springer-Verlag. 1998; 377.
  • NIAAA (National Institute on Alcohol Abuse and Alcoholism), Alcohol Health Services Research, U.S. Department of Health and Human Services, NIH. 10th Special Report to the U.S. Congress on Alcohol and Health. 2000.
  • Ramaiah S, Rivera C, and Arteel G. Early-phase alcoholic liver disease: an update on animal models, pathology, and pathogenesis. Int J Toxicol 2004; 23: 217–231.
  • Ivester P, Roberts LJ, II, Young T, Stafforini D, Vivian J, Lees C, Young J, Daunais J, Friedman D, Rippe RA, Parsons CJ, Grant KA, and Cunningham C. Etanol Self-Administration and Alterations in the Livers of the Cynomolgus Monkey, Macaca fascicularis. Alcohol Clin Exp Res 2007; 31(1): 144–155.
  • Sorensen TI, Orholm M, Bentsen KD, Hoybye G, Eghoje K, and Christoffersen P. Prospective evaluation of alcohol abuse and alcoholic liver injury in men as predictors of development of cirrhosis. Lancet 1984; 2: 241–244.
  • Worner TM, and Lieber CS. Perivenular fibrosis as precursor lesion of cirrhosis. JAMA 1985; 254: 627–630.
  • Schuppan D, Atkinson J, Ruehl M, Riecken EO.
  • Alcohol and liver fibrosis-- pathobiochemistry and treatment. Gastroenterol 1995; 33:546-550.
  • Lieber CS. Alcoholic liver injury: pathogenesis and therapy in Pathol Biol (Paris) 2001; 49: 738-752.
  • Lieber CS. Etanol metabolism, cirrhosis and alcoholism. Clin Chim Acta 1997; 257: 59-84.
  • Rognstead R, and Grunnet N. Enzymatic pathways of etanol metabolism. In E. Majchrowicz, & E. P. Noble (Eds.), Biochemistry and Pharmacology of Etanol 1979; 65–86. New York, NY: Plenum Press.
  • Kessova IG, Cederbaum AI. The effect of CYP2E1- dependent oxidant stress on activity of proteasomes in HepG2 cells. J Pharmacol Exp Ther 2005; 315: 304- 312.
  • Osna NA, Haorah J, Krutik VM, Donohue TM Jr. Peroxynitrite alters the catalytic activity of rodent liver proteasome in vitro and in vivo. Hepatology 2004; 40:574-582.
  • Donohue TM, Osna NA, Clemens DL. Recombinant Hep G2 cells that express alcohol dehydrogenase and cytochrome P450 2E1 as a model of etanol-elicited cytotoxicity. Int J Biochem Cell Biol 2006; 38:92-101.
  • Osna NA, Clemens DL, Donohue TM Jr. Interferon gamma enhances proteasome activity in recombinant Hep G2 cells that express cytochrome P4502E1: modulation by etanol. Biochem Pharmacol 2003; 66:697-710.
  • Osna NA, Clemens DL, Donohue TM Jr. Etanol metabolism alters interferon gamma signaling in recombinant HepG2 cells. Hepatology 2005; 42:1109- 1117.
  • Nuutinen H, Lindros KO, and Salaspuro M. Determinants of blood acetaldehyde level during etanol oxidation in chronic alcoholics. Alcohol Clin Exp Res 1983; 7: 163–168.
  • Palmer KR, and Jenkins W J. Aldehyde dehydrogenase in alcoholic subjects. Hepatology 1985; 5: 260–263.
  • Panes J, Soler X, Pares A, Pares A, Caballeria J, Farres J, Rodes J, and Pares X. Influence of liver disease on hepatic alcohol and aldehyde dehydrogenases. Gastroenterology 1989; 97: 708–714.
  • Panes J, Caballeria J, Guitart R, Pares A, Soler X, Rodamilans M, Navasa M, Pares X, Bosch J, and Rodes J. Determinants of etanol and acetaldehyde metabolism in chronic alcoholics. Alcohol Clin Exp Res 1993; 17: 48–53.
  • Cigremis Y, Turkoz Y, Tuzcu M, Ozen H, Kart A, Gaffaroglu M, Erdogan K, Akgoz M, and Ozugurlu F. The effects of chronic exposure to etanol and cigarette smoke on the formation of peroxynitrite, level of nitric oxide, xanthine oxidase and myeloperoxidase activities in rat kidney. Molecul Cell Biochem 2006; 291: 127–138.
  • Rodrigo R, and Bosco C. Oxidative stress and protective effects of polyphenols: Comparative studies in human and rodent kidney. A review. Comp Biochem and Physiol, Part C 2006; 142: 317–327.
  • Jurczuk M, Moniuszko-Jakoniuk J, Brz´oska MM. Involvement of some low-molecular thiols in the peroxidative mechanisms of lead and etanol action on rat liver and kidney. Toxicology 2006; 219: 11–21.
  • Ozturk H, Yagmur Y, Buyukbayram H. The effect of L-arginine methyl ester on indices of free radical involvement in a rat model of experimental nephrocalcinosis. Urol Res 2006; 34:305–314.
  • Keller CK, Andrassy K, Waldherr R, Ritz E. Post infectious glomerulonephritis-is there a link to alcoholism? Q J Med 1994; 87: 97–102.
  • Hirsch DJ, Jindal KK, Trillo A, Cohen AD. Acute renal failure after binge drinking. Nephrol Dial Transplant 1994; 9:330–331.
  • De Marchi S, Cecchin E, Basile A, Bertotti A, Nardini R, Bartoli E. Renal tubular dysfunction in chronic alcohol abuse-effects of abstinence. N Engl J Med 1994; 329: 1927–1934.
  • Greene EL, Paller MS. Oxygen free radicals in acute renal failure. Miner Electrol Metab 1991; 17:124–132.
  • Ribeiro MO, Antunes E, de Nucci G, et al. Chronic arginin inhibition of nitric oxide synthesis. A new model of arterial hypertension. Hypertension 1992; 20:298–303.
  • Baylis C, Mitruka B, Deng A. Chronic blockade of nitric oxide synthesis in the rat produces systemic hypertension and glomerular damage. J Clin Invest 1992; 90:278–281.
  • Jover B, Herizi A, Ventre F, et al. Sodium and angiotensin in hypertension induced by long-term nitric oxide blockade. Hypertension 1993; 21:944–948.
  • Navarro J, Sanchez A, Saiz J, et al. Hormonal, renal and metabolic alterations during the hypertension induced by chronic inhibition of nitric oxide in rats. Am J Physiol 1994; 267: R1516–R1521.
  • Caban A, Oczkowicz G, Abdel-Samad O, and Cierpka L. Influence of Ischemic Preconditioning and Nitric Oxide on Microcirculation and the Degree of Rat Liver Injury in the Model of Ischemia and Reperfusion. Transplant Proceed 2006; 38: 196–198.
  • Pawlosky RJ, Salem N Jr. Development of alcoholic fatty liver and fibrosis in rhesus monkeys fed a low n- 3 fatty acid diet. Alcohol Clin Exp Res 2004; 28:1569–1576.
  • Lieber CS, DeCarli LM. Animal models of etanol dependence and liver injury in rats and baboons. Fed Proc 1976; 35:1232–1236.
  • Bhopale KK, Wu H, Boor PJ, Popov VL, Ansari GAS, Kaphalia BS. Metabolic basis of etanol-induced hepatic and pancreatic injury in hepatic alcohol dehydrogenase deficient deer mice Alcohol 2006; 39: 179-188.
  • Popper H, Lieber CS. Histogenesis of alcoholic fibrosis and cirrhosis in the baboon. Am J Pathol 1980; 98:695–716.
  • Freeman BA, Crapo JD. Biology of disease: free radicals and tissue injury. Lab Invest 1982; 47: 412–426.
  • Mantle D, Preedy VR. Free radicals as mediators of alcohol toxicity. Adverse Drug React Toxicol Rev 1999; 18: 235–252.
  • Klahr S. Oxygen radicals and renal diseases. Miner Electrol Metab 1997; 23: 140–143.
  • Thamilselvan S, Byer KJ, Hackett RL, Khan SR. Free radical scavengers, catalase and superoxide dismutase provide protection from oxalate-associated injury to LLC-PK1 and MDCK cells. J Urol 2000; 164:224–229.
  • Toba H, Nakagawa Y, Miki S, Shimizu T, Yoshimura A, Inoue R, Asayama J, Kobara M, Nakata T: Calcium channel blockades exhibit anti-inflammatory and antioxidative effects by augmentation of endothelial nitric oxide synthase and the inhibition of angiotensin converting enzyme in the N(G)-nitro-L-arginine methyl ester-induced hypertensive rat aorta: vasoprotective effects beyond the blood pressure-lowering effects of amlodipine and manidipine. Hypertens Res 2005; 28(8): 689-700.
  • Somani S.M. & Husain K. Interaction of exercise training and chronic ethanol ingestion on antioxidant system of rat brain regions. J Appl Toxicol 1997, 17, 329-336.
Year 2008, Volume: 15 Issue: 4, 11 - 17, 29.05.2009

Abstract

References

  • Sivapiriya V, Jayanthisakthisekaran, Venkatraman S. Effects of dimethoate (O,O-dimethyl S-methyl carbamoyl methyl phosphorodithioate) and Etanol in antioxidant status of liver and kidney of experimental mice. Pesticide Biochemistry and Physiology June 2006; 85(2): 115 -121.
  • Scott RB, Reddy KS, Husain K, Schlorff EC, Rybak LP, Somani SM. Dose response of etanol on antioxidant defense system of liver, lung, and kidney in rat. Pathophysiology 2000; 7: 25–32.
  • Majchrowicz E. Induction of physical dependance upon etanol and the associated behavioral changes in rats. Psychopharmachologia 1975; 43; 245–254.
  • Bondy SC, Etanol toxicity and oxidative stress. Toxicol. Lett. 1992; 63: 231–241.
  • Lankisch PG, and Banks PA. Pancreatitis New York, Berlin, Heidelberg: Springer-Verlag. 1998; 377.
  • NIAAA (National Institute on Alcohol Abuse and Alcoholism), Alcohol Health Services Research, U.S. Department of Health and Human Services, NIH. 10th Special Report to the U.S. Congress on Alcohol and Health. 2000.
  • Ramaiah S, Rivera C, and Arteel G. Early-phase alcoholic liver disease: an update on animal models, pathology, and pathogenesis. Int J Toxicol 2004; 23: 217–231.
  • Ivester P, Roberts LJ, II, Young T, Stafforini D, Vivian J, Lees C, Young J, Daunais J, Friedman D, Rippe RA, Parsons CJ, Grant KA, and Cunningham C. Etanol Self-Administration and Alterations in the Livers of the Cynomolgus Monkey, Macaca fascicularis. Alcohol Clin Exp Res 2007; 31(1): 144–155.
  • Sorensen TI, Orholm M, Bentsen KD, Hoybye G, Eghoje K, and Christoffersen P. Prospective evaluation of alcohol abuse and alcoholic liver injury in men as predictors of development of cirrhosis. Lancet 1984; 2: 241–244.
  • Worner TM, and Lieber CS. Perivenular fibrosis as precursor lesion of cirrhosis. JAMA 1985; 254: 627–630.
  • Schuppan D, Atkinson J, Ruehl M, Riecken EO.
  • Alcohol and liver fibrosis-- pathobiochemistry and treatment. Gastroenterol 1995; 33:546-550.
  • Lieber CS. Alcoholic liver injury: pathogenesis and therapy in Pathol Biol (Paris) 2001; 49: 738-752.
  • Lieber CS. Etanol metabolism, cirrhosis and alcoholism. Clin Chim Acta 1997; 257: 59-84.
  • Rognstead R, and Grunnet N. Enzymatic pathways of etanol metabolism. In E. Majchrowicz, & E. P. Noble (Eds.), Biochemistry and Pharmacology of Etanol 1979; 65–86. New York, NY: Plenum Press.
  • Kessova IG, Cederbaum AI. The effect of CYP2E1- dependent oxidant stress on activity of proteasomes in HepG2 cells. J Pharmacol Exp Ther 2005; 315: 304- 312.
  • Osna NA, Haorah J, Krutik VM, Donohue TM Jr. Peroxynitrite alters the catalytic activity of rodent liver proteasome in vitro and in vivo. Hepatology 2004; 40:574-582.
  • Donohue TM, Osna NA, Clemens DL. Recombinant Hep G2 cells that express alcohol dehydrogenase and cytochrome P450 2E1 as a model of etanol-elicited cytotoxicity. Int J Biochem Cell Biol 2006; 38:92-101.
  • Osna NA, Clemens DL, Donohue TM Jr. Interferon gamma enhances proteasome activity in recombinant Hep G2 cells that express cytochrome P4502E1: modulation by etanol. Biochem Pharmacol 2003; 66:697-710.
  • Osna NA, Clemens DL, Donohue TM Jr. Etanol metabolism alters interferon gamma signaling in recombinant HepG2 cells. Hepatology 2005; 42:1109- 1117.
  • Nuutinen H, Lindros KO, and Salaspuro M. Determinants of blood acetaldehyde level during etanol oxidation in chronic alcoholics. Alcohol Clin Exp Res 1983; 7: 163–168.
  • Palmer KR, and Jenkins W J. Aldehyde dehydrogenase in alcoholic subjects. Hepatology 1985; 5: 260–263.
  • Panes J, Soler X, Pares A, Pares A, Caballeria J, Farres J, Rodes J, and Pares X. Influence of liver disease on hepatic alcohol and aldehyde dehydrogenases. Gastroenterology 1989; 97: 708–714.
  • Panes J, Caballeria J, Guitart R, Pares A, Soler X, Rodamilans M, Navasa M, Pares X, Bosch J, and Rodes J. Determinants of etanol and acetaldehyde metabolism in chronic alcoholics. Alcohol Clin Exp Res 1993; 17: 48–53.
  • Cigremis Y, Turkoz Y, Tuzcu M, Ozen H, Kart A, Gaffaroglu M, Erdogan K, Akgoz M, and Ozugurlu F. The effects of chronic exposure to etanol and cigarette smoke on the formation of peroxynitrite, level of nitric oxide, xanthine oxidase and myeloperoxidase activities in rat kidney. Molecul Cell Biochem 2006; 291: 127–138.
  • Rodrigo R, and Bosco C. Oxidative stress and protective effects of polyphenols: Comparative studies in human and rodent kidney. A review. Comp Biochem and Physiol, Part C 2006; 142: 317–327.
  • Jurczuk M, Moniuszko-Jakoniuk J, Brz´oska MM. Involvement of some low-molecular thiols in the peroxidative mechanisms of lead and etanol action on rat liver and kidney. Toxicology 2006; 219: 11–21.
  • Ozturk H, Yagmur Y, Buyukbayram H. The effect of L-arginine methyl ester on indices of free radical involvement in a rat model of experimental nephrocalcinosis. Urol Res 2006; 34:305–314.
  • Keller CK, Andrassy K, Waldherr R, Ritz E. Post infectious glomerulonephritis-is there a link to alcoholism? Q J Med 1994; 87: 97–102.
  • Hirsch DJ, Jindal KK, Trillo A, Cohen AD. Acute renal failure after binge drinking. Nephrol Dial Transplant 1994; 9:330–331.
  • De Marchi S, Cecchin E, Basile A, Bertotti A, Nardini R, Bartoli E. Renal tubular dysfunction in chronic alcohol abuse-effects of abstinence. N Engl J Med 1994; 329: 1927–1934.
  • Greene EL, Paller MS. Oxygen free radicals in acute renal failure. Miner Electrol Metab 1991; 17:124–132.
  • Ribeiro MO, Antunes E, de Nucci G, et al. Chronic arginin inhibition of nitric oxide synthesis. A new model of arterial hypertension. Hypertension 1992; 20:298–303.
  • Baylis C, Mitruka B, Deng A. Chronic blockade of nitric oxide synthesis in the rat produces systemic hypertension and glomerular damage. J Clin Invest 1992; 90:278–281.
  • Jover B, Herizi A, Ventre F, et al. Sodium and angiotensin in hypertension induced by long-term nitric oxide blockade. Hypertension 1993; 21:944–948.
  • Navarro J, Sanchez A, Saiz J, et al. Hormonal, renal and metabolic alterations during the hypertension induced by chronic inhibition of nitric oxide in rats. Am J Physiol 1994; 267: R1516–R1521.
  • Caban A, Oczkowicz G, Abdel-Samad O, and Cierpka L. Influence of Ischemic Preconditioning and Nitric Oxide on Microcirculation and the Degree of Rat Liver Injury in the Model of Ischemia and Reperfusion. Transplant Proceed 2006; 38: 196–198.
  • Pawlosky RJ, Salem N Jr. Development of alcoholic fatty liver and fibrosis in rhesus monkeys fed a low n- 3 fatty acid diet. Alcohol Clin Exp Res 2004; 28:1569–1576.
  • Lieber CS, DeCarli LM. Animal models of etanol dependence and liver injury in rats and baboons. Fed Proc 1976; 35:1232–1236.
  • Bhopale KK, Wu H, Boor PJ, Popov VL, Ansari GAS, Kaphalia BS. Metabolic basis of etanol-induced hepatic and pancreatic injury in hepatic alcohol dehydrogenase deficient deer mice Alcohol 2006; 39: 179-188.
  • Popper H, Lieber CS. Histogenesis of alcoholic fibrosis and cirrhosis in the baboon. Am J Pathol 1980; 98:695–716.
  • Freeman BA, Crapo JD. Biology of disease: free radicals and tissue injury. Lab Invest 1982; 47: 412–426.
  • Mantle D, Preedy VR. Free radicals as mediators of alcohol toxicity. Adverse Drug React Toxicol Rev 1999; 18: 235–252.
  • Klahr S. Oxygen radicals and renal diseases. Miner Electrol Metab 1997; 23: 140–143.
  • Thamilselvan S, Byer KJ, Hackett RL, Khan SR. Free radical scavengers, catalase and superoxide dismutase provide protection from oxalate-associated injury to LLC-PK1 and MDCK cells. J Urol 2000; 164:224–229.
  • Toba H, Nakagawa Y, Miki S, Shimizu T, Yoshimura A, Inoue R, Asayama J, Kobara M, Nakata T: Calcium channel blockades exhibit anti-inflammatory and antioxidative effects by augmentation of endothelial nitric oxide synthase and the inhibition of angiotensin converting enzyme in the N(G)-nitro-L-arginine methyl ester-induced hypertensive rat aorta: vasoprotective effects beyond the blood pressure-lowering effects of amlodipine and manidipine. Hypertens Res 2005; 28(8): 689-700.
  • Somani S.M. & Husain K. Interaction of exercise training and chronic ethanol ingestion on antioxidant system of rat brain regions. J Appl Toxicol 1997, 17, 329-336.
There are 47 citations in total.

Details

Primary Language English
Journal Section Araştırma Makaleleri
Authors

Recep Kutlubay This is me

Emin Oğuz This is me

Günfer Turgut This is me

Erdoğan Kocamaz This is me

Publication Date May 29, 2009
Submission Date May 28, 2009
Published in Issue Year 2008 Volume: 15 Issue: 4

Cite

Vancouver Kutlubay R, Oğuz E, Turgut G, Kocamaz E. Karaciğer ve böbrek üzerine etanolün toksisitesi ve L-NAME. in koruyucu etkisi. Med J SDU. 2009;15(4):11-7.

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