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Lung Tissue Damage in the Experimental Carbon Tetrachloride Toxicity and Protective Role of Melatonin Hormone: A light Microscopic and Biochemical Study

Year 2012, Volume: 14 Issue: 3, 37 - 42, 01.12.2012

Abstract

In this study, it was aimed to investigate the protective effects of melatonin hormone against tocarbon tetrachloride (CCl4)-induced toxicity in lung tissue. Twenty-four male Wistar-Albinorats were randomly divided into three equal groups. Rats in group I were used as control. Ratsin group II were injected subcutaneously every other day with CCl4. Rats in group III wereinjected subcutaneously every other day with CCl4 and melatonin. At the end of four weeks ofexperimental period, all animals were killed by decapitation and their lungs were removed. Forbiochemical examination, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)enzyme activities and malondialdehyde (MDA) levels were determinated by aspectrophotometer in some of the lung tissue specimens. For light microscopic examination,tissue specimens were embedded in paraffin blocks following routine histological procedures.In lung tissue samples of rats treated with CCl4, SOD and GSH-Px enzyme activities weresignificantly lower and malondialdehyde (MDA) levels were significantly higher than thecontrol group. Microscopically, interstitial pulmonary hemorrhage, leucocytes with polymorphicnuclei and macrophage infiltration were observed in the lung specimens of rats exposed to CCl4alone.There is a statistically significant increase in SOD and GSH-Px enzyme activities, and adecrease in MDA levels in rats treated with CCl4 and melatonin. Histopathological changescaused by CCl4 toxicity were not observed in rats treated by melatonin. It is concluded thatCCl4 creates oxidative damage in lung tissue and melatonin has protective effects against thisCCl4 induced damage.Anahtar kelimeler: Lung, CCl4, oxidative stress, rat

References

  • Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for carbon tetrachloride. Atlanta: U.S. Department of Health and Human Services, Public Health Service; 2005.
  • Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol. 2003;33(2):105-36.
  • Thrall KD, Vucelick ME, Gies RA, et al. Comparative metabolism of carbon tetrachloride in rats, mice, and hamsters using gas uptake and PBPK modeling. J Toxicol Environ Health A 2000; 60: 531-48.
  • Ohta Y, Kongo M, Sasaki E, Nishida K, Ishiguro I. Therapeutic effect of melatonin on carbon tetrachloride- induced acute liver injury in rats. J Pineal Res 2000; 28: 119-26.
  • Rao PS, Mangipudy RS, Mehendale HM. Tissue injury and repair as parallel and opposing responses to CCl4 hepatotoxicity: a novel dose-response. Toxicology 1997; 118: 181-93.
  • Abraham P, Wilfred G, Cathrine S.P. Oxidative damage to the lipids and proteins pf the lungs, testis and kidney of rats during carbon tetrachloride intoxication. Clin Chim Acta. 1999 Nov;289(1-2):177-9.
  • Paakko P, Ala-Kokko L, Ryhanen L. A light microscopic and biochemical study of carbon tetrachloride-induced pulmonary fibrosis in rats: the preventive effect of malotilate. Eur J Clin Invest 1987; 17(4):340-6.
  • Paakko P, Anttila S, Sormunen R, Ala-Kokko L, Peura R, Ferrans VJ, Ryhanen L. Biochemical and morphological characterization of carbon tetrachloride-induced lung fibrosis in rats. Arch Toxicol 1996;70(9):540-52.
  • Miyamoto K. Experimental study on changes of the pulmonary vessels in the cirrhotic rats. Nippon Geka Gakkai Zasshi 1995; 96(1):44-53.
  • Furukawa T, Yasumoto K, Inokunchi K. Pulmonary interstitial edema in experimental cirrhosis of the liver in rats. Eur Surg Res 1984;16(6):366-71.
  • Chen WJ, Chi EY, Smuckler EA. Carbon tetrachloride- induced changes in mixed function oxidases and microsomal cytochromes in the rat lung. Lab invest 1977; 36(4):388-94.
  • Zhang HQ, Yau YF, Szeto KY, Chan WT, Wong J, Li M. Therapeutic effect of Chinese medicine formula DSQRL on experimental pulmonary fibrosis. J Ethnopharmacol 2007; 109 (3): 543-546.
  • Nagano K, Sasaki T, Umeda Y, Nishizawa T, Ikawa N, Ohbayashi H, Arito H, Yamamoto S, Fukushima S. Inhalation carcinogenicity and chronic toxicity of carbon tetrachloride in rats and mice. Inhal Toxicol 2007; 19(13):1089-103.
  • Kuş İ, Sarsılmaz M. Pineal bezin morfolojik yapısı ve fonksiyonları. T Klin J Med Sci 2002; 22: 221-226.
  • Kus I, Akpolat N, Ozen OA, et al. Effects of melatonin on Leydig cells in pinealectomized rat: an immunohistochemical study. Acta Histochem 2002; 104: 93-97.
  • Guerrero JM, Reiter RJ. A brief survey of pineal gland- immune system interrelationships. Endocr Res 1992; 18: 91-113.
  • Ayar A, Kutlu S, Yilmaz B, Kelestimur H. Melatonin inhibits spontaneous and oxytocin-induced contractions of rat myometrium in vitro. Neuroendocrinol Lett 2001; 22: 301- 306.
  • Stastica P, Ulanski P, Rosiak JM. Melatonin as a hydroxyl radical scavenger. J Pineal Res 1998; 25: 65-66.
  • Zang LY, Cosma G, Gardner H, Vallyathan V. Scavenging of reactive oxygen species by melatonin. Biochim Biophys Acta 1998; 1425: 469-477.
  • Longoni B, Salgo MG, Pryor WA, Marchiafava PL. Effects of melatonin on lipid peroxidation induced by oxygen radicals. Life Sci 1998; 62: 853-859.
  • Sewerynek E, Melchiorri DA, Chen L, Reiter RJ. Melatonin reduces both basal and bacterial lipopolysaccharide-induced lipid peroxidation in vitro. Free Radic Biol Med 1995; 19: 903-909.
  • Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988; 34: 497-500.
  • Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterisation of erythrocyte glutathione peroxidase. J Lab Clin Med 1967; 70: 158-169.
  • Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4- hidroxynonenal. Methods Enzymol 1990; 186: 407-421.
  • Manautou JE, Silva VM, Hennig GE, Whiteley HE. Repeated dosing with the peroxisome proliferator clofibrate decreases the toxicity of model hepatotoxic agents in male mice. Toxicology 1998; 127: 1-10.
  • Mbonifor JN, Chigbo FE, Mehendale HM. Polyamine Protection Against Chemically Induced Hepatotoxicity. Int J Toxicol 2000; 19: 391-400.
  • Wirth KJ, Bickel M, Hropot M, et al. The bradykinin B2 receptor antagonist Icatibant (HOE 140) corrects avid Na+ retention in rats with CCl4-induced liver cirrhosis: possible role of enhanced microvascular leakage. Eur J Pharmacol 1997; 337: 45-53.
  • Akyol Ö. Beyin tümörlerinde doku SOD, CAT ve GSH-Px aktiviteleri. Uzmanlık tezi, Ankara: Ankara Üniversitesi Tıp Fakültesi, Biyokimya Bölümü, Ankara 1994.
  • Ganie SA, Haq E, Hamid A, Qurishi Y, Mahmood Z, Zargar BA. Carbon tetrachloride induced kidney and lung tissue damages and antioxidant activities of the aqueous rhizome extract of Podophyllum hexandrum. BMC Complement Altern Med 2011; 28: 11:17.
  • Kamal AA, Gomaa A, el Khafif M, Hammad AS. Plasma lipid peroxides among workers exposed to silica or asbestos dust. Environ Res 1989; 49: 173-180.
  • Reiter RJ, Carneiro RC, Oh CS. Melatonin in relation to cellular antioxidative defense mechanisms. Horm Metab Res 1997; 29: 363-372.
  • Kus I, Ogeturk M, Oner H, Sahin S, Yekeler H, Sarsilmaz M. Protective effects of melatonin against carbon tetrachloride- induced hepatotoxicity in rats: a light microscopic and biochemical study. Cell Biochem Funct 2005; 23: 169-174.
  • Ogeturk M, Kus I, Kavakli A, Oner J, Kukner A, Sarsilmaz M. Reduction of carbon tetrachloride-induced nephropathy by melatonin administration. Cell Biochem Funct 2005; 23: 85-92.
  • Ogeturk M, Kus I, Pekmez H, Sahin S, Sarsilmaz M. Inhibition of carbon tetrachloride–mediated apoptosis and oxidative stress by melatonin in experimental liver fibrosis. Toxicology and Industrial Health 2008; 24: 201-208.

Deneysel Karbon Tetraklorür Zehirlenmesinde Akciğer Doku Hasarı ve Melatonin Hormonunun Koruyucu Rolü: Işık Mikroskobik ve Biyokimyasal Bir Çalışma

Year 2012, Volume: 14 Issue: 3, 37 - 42, 01.12.2012

Abstract

Bu çalışmada, akciğer dokusu üzerindeki karbon tetraklorür (CCl4) toksisitesine karşı melatoninhormonunun koruyucu etkisinin incelenmesi amaçlandı. 24 adet Wistar-Albino cinsi erkeksıçanlar üç eşit gruba ayrıldı. Grup I’deki sıçanlar kontrol olarak kullanıldı. Grup II’dekihayvanlara gün aşırı olarak ve derialtı yolla CCl4 uygulandı. Grup III’deki sıçanlara ise CCl4enjeksiyonu ile birlikte yine gün aşırı olarak ve derialtı yolla melatonin verildi. Dört haftalıkdeney süresi sonunda bütün sıçanlar dekapite edilerek akciğerleri çıkartıldı. Biyokimyasalincelemeler için, akciğer doku örneklerinin bir bölümünde süperoksit dismutaz (SOD), glutatyonperoksidaz (GSH-Px) enzim aktiviteleri ve malondialdehit (MDA) seviyeleri spektrofotometrikolarak belirlendi. Mikroskobik incelemeler için, doku örnekleri rutin histolojik prosedürlerdengeçirilerek parafine gömüldü. CCl4 enjeksiyonu yapılan sıçanlara ait akciğer dokuörneklerindeki SOD ve GSH-Px enzim aktivitelerinin kontrol grubuna göre istatistiksel olarakanlamlı bir şekilde azaldığı, MDA düzeylerinin ise arttığı tespit edildi. Mikroskobik incelemedeise, CCl4 maruziyetinin akciğerde pulmoner interstisyumda hemoraji’ye, polimorf çekirdeklilökosit ve makrofaj infiltrasyonuna neden olduğu görüldü. CCl4 enjeksiyonu ile birliktemelatonin uygulanan hayvanlarda, SOD ve GSH-Px enzim aktivitelerinde bir artışın meydanageldiği, MDA değerlerinde ise anlamlı bir düşüşün olduğu gözlendi. Işık mikroskobikincelemelerde, CCl4 toksisitesinin neden olduğu histopatolojik değişikliklerin melatoninuygulamasıyla düzeldiği görüldü. CCl4 toksisitesinin akciğerlerde önemli ölçüde oksidatif dokuhasarına yol açtığı ve bu hasarın melatonin uygulamasıyla önlenebildiği tespit edildi

References

  • Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for carbon tetrachloride. Atlanta: U.S. Department of Health and Human Services, Public Health Service; 2005.
  • Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol. 2003;33(2):105-36.
  • Thrall KD, Vucelick ME, Gies RA, et al. Comparative metabolism of carbon tetrachloride in rats, mice, and hamsters using gas uptake and PBPK modeling. J Toxicol Environ Health A 2000; 60: 531-48.
  • Ohta Y, Kongo M, Sasaki E, Nishida K, Ishiguro I. Therapeutic effect of melatonin on carbon tetrachloride- induced acute liver injury in rats. J Pineal Res 2000; 28: 119-26.
  • Rao PS, Mangipudy RS, Mehendale HM. Tissue injury and repair as parallel and opposing responses to CCl4 hepatotoxicity: a novel dose-response. Toxicology 1997; 118: 181-93.
  • Abraham P, Wilfred G, Cathrine S.P. Oxidative damage to the lipids and proteins pf the lungs, testis and kidney of rats during carbon tetrachloride intoxication. Clin Chim Acta. 1999 Nov;289(1-2):177-9.
  • Paakko P, Ala-Kokko L, Ryhanen L. A light microscopic and biochemical study of carbon tetrachloride-induced pulmonary fibrosis in rats: the preventive effect of malotilate. Eur J Clin Invest 1987; 17(4):340-6.
  • Paakko P, Anttila S, Sormunen R, Ala-Kokko L, Peura R, Ferrans VJ, Ryhanen L. Biochemical and morphological characterization of carbon tetrachloride-induced lung fibrosis in rats. Arch Toxicol 1996;70(9):540-52.
  • Miyamoto K. Experimental study on changes of the pulmonary vessels in the cirrhotic rats. Nippon Geka Gakkai Zasshi 1995; 96(1):44-53.
  • Furukawa T, Yasumoto K, Inokunchi K. Pulmonary interstitial edema in experimental cirrhosis of the liver in rats. Eur Surg Res 1984;16(6):366-71.
  • Chen WJ, Chi EY, Smuckler EA. Carbon tetrachloride- induced changes in mixed function oxidases and microsomal cytochromes in the rat lung. Lab invest 1977; 36(4):388-94.
  • Zhang HQ, Yau YF, Szeto KY, Chan WT, Wong J, Li M. Therapeutic effect of Chinese medicine formula DSQRL on experimental pulmonary fibrosis. J Ethnopharmacol 2007; 109 (3): 543-546.
  • Nagano K, Sasaki T, Umeda Y, Nishizawa T, Ikawa N, Ohbayashi H, Arito H, Yamamoto S, Fukushima S. Inhalation carcinogenicity and chronic toxicity of carbon tetrachloride in rats and mice. Inhal Toxicol 2007; 19(13):1089-103.
  • Kuş İ, Sarsılmaz M. Pineal bezin morfolojik yapısı ve fonksiyonları. T Klin J Med Sci 2002; 22: 221-226.
  • Kus I, Akpolat N, Ozen OA, et al. Effects of melatonin on Leydig cells in pinealectomized rat: an immunohistochemical study. Acta Histochem 2002; 104: 93-97.
  • Guerrero JM, Reiter RJ. A brief survey of pineal gland- immune system interrelationships. Endocr Res 1992; 18: 91-113.
  • Ayar A, Kutlu S, Yilmaz B, Kelestimur H. Melatonin inhibits spontaneous and oxytocin-induced contractions of rat myometrium in vitro. Neuroendocrinol Lett 2001; 22: 301- 306.
  • Stastica P, Ulanski P, Rosiak JM. Melatonin as a hydroxyl radical scavenger. J Pineal Res 1998; 25: 65-66.
  • Zang LY, Cosma G, Gardner H, Vallyathan V. Scavenging of reactive oxygen species by melatonin. Biochim Biophys Acta 1998; 1425: 469-477.
  • Longoni B, Salgo MG, Pryor WA, Marchiafava PL. Effects of melatonin on lipid peroxidation induced by oxygen radicals. Life Sci 1998; 62: 853-859.
  • Sewerynek E, Melchiorri DA, Chen L, Reiter RJ. Melatonin reduces both basal and bacterial lipopolysaccharide-induced lipid peroxidation in vitro. Free Radic Biol Med 1995; 19: 903-909.
  • Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988; 34: 497-500.
  • Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterisation of erythrocyte glutathione peroxidase. J Lab Clin Med 1967; 70: 158-169.
  • Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4- hidroxynonenal. Methods Enzymol 1990; 186: 407-421.
  • Manautou JE, Silva VM, Hennig GE, Whiteley HE. Repeated dosing with the peroxisome proliferator clofibrate decreases the toxicity of model hepatotoxic agents in male mice. Toxicology 1998; 127: 1-10.
  • Mbonifor JN, Chigbo FE, Mehendale HM. Polyamine Protection Against Chemically Induced Hepatotoxicity. Int J Toxicol 2000; 19: 391-400.
  • Wirth KJ, Bickel M, Hropot M, et al. The bradykinin B2 receptor antagonist Icatibant (HOE 140) corrects avid Na+ retention in rats with CCl4-induced liver cirrhosis: possible role of enhanced microvascular leakage. Eur J Pharmacol 1997; 337: 45-53.
  • Akyol Ö. Beyin tümörlerinde doku SOD, CAT ve GSH-Px aktiviteleri. Uzmanlık tezi, Ankara: Ankara Üniversitesi Tıp Fakültesi, Biyokimya Bölümü, Ankara 1994.
  • Ganie SA, Haq E, Hamid A, Qurishi Y, Mahmood Z, Zargar BA. Carbon tetrachloride induced kidney and lung tissue damages and antioxidant activities of the aqueous rhizome extract of Podophyllum hexandrum. BMC Complement Altern Med 2011; 28: 11:17.
  • Kamal AA, Gomaa A, el Khafif M, Hammad AS. Plasma lipid peroxides among workers exposed to silica or asbestos dust. Environ Res 1989; 49: 173-180.
  • Reiter RJ, Carneiro RC, Oh CS. Melatonin in relation to cellular antioxidative defense mechanisms. Horm Metab Res 1997; 29: 363-372.
  • Kus I, Ogeturk M, Oner H, Sahin S, Yekeler H, Sarsilmaz M. Protective effects of melatonin against carbon tetrachloride- induced hepatotoxicity in rats: a light microscopic and biochemical study. Cell Biochem Funct 2005; 23: 169-174.
  • Ogeturk M, Kus I, Kavakli A, Oner J, Kukner A, Sarsilmaz M. Reduction of carbon tetrachloride-induced nephropathy by melatonin administration. Cell Biochem Funct 2005; 23: 85-92.
  • Ogeturk M, Kus I, Pekmez H, Sahin S, Sarsilmaz M. Inhibition of carbon tetrachloride–mediated apoptosis and oxidative stress by melatonin in experimental liver fibrosis. Toxicology and Industrial Health 2008; 24: 201-208.
There are 34 citations in total.

Details

Primary Language Turkish
Journal Section Research Article
Authors

Burak Gülcen This is me

Murat Abdülgani Kuş This is me

Serdar Çolakoğlu This is me

Murat Ögetürk This is me

İlter Kuş This is me

Mehmet Akif Ersoy This is me

Ömür Karaca This is me

Publication Date December 1, 2012
Published in Issue Year 2012 Volume: 14 Issue: 3

Cite

APA Gülcen, B., Kuş, M. A., Çolakoğlu, S., Ögetürk, M., et al. (2012). Deneysel Karbon Tetraklorür Zehirlenmesinde Akciğer Doku Hasarı ve Melatonin Hormonunun Koruyucu Rolü: Işık Mikroskobik ve Biyokimyasal Bir Çalışma. Duzce Medical Journal, 14(3), 37-42.
AMA Gülcen B, Kuş MA, Çolakoğlu S, Ögetürk M, Kuş İ, Ersoy MA, Karaca Ö. Deneysel Karbon Tetraklorür Zehirlenmesinde Akciğer Doku Hasarı ve Melatonin Hormonunun Koruyucu Rolü: Işık Mikroskobik ve Biyokimyasal Bir Çalışma. Duzce Med J. December 2012;14(3):37-42.
Chicago Gülcen, Burak, Murat Abdülgani Kuş, Serdar Çolakoğlu, Murat Ögetürk, İlter Kuş, Mehmet Akif Ersoy, and Ömür Karaca. “Deneysel Karbon Tetraklorür Zehirlenmesinde Akciğer Doku Hasarı Ve Melatonin Hormonunun Koruyucu Rolü: Işık Mikroskobik Ve Biyokimyasal Bir Çalışma”. Duzce Medical Journal 14, no. 3 (December 2012): 37-42.
EndNote Gülcen B, Kuş MA, Çolakoğlu S, Ögetürk M, Kuş İ, Ersoy MA, Karaca Ö (December 1, 2012) Deneysel Karbon Tetraklorür Zehirlenmesinde Akciğer Doku Hasarı ve Melatonin Hormonunun Koruyucu Rolü: Işık Mikroskobik ve Biyokimyasal Bir Çalışma. Duzce Medical Journal 14 3 37–42.
IEEE B. Gülcen, M. A. Kuş, S. Çolakoğlu, M. Ögetürk, İ. Kuş, M. A. Ersoy, and Ö. Karaca, “Deneysel Karbon Tetraklorür Zehirlenmesinde Akciğer Doku Hasarı ve Melatonin Hormonunun Koruyucu Rolü: Işık Mikroskobik ve Biyokimyasal Bir Çalışma”, Duzce Med J, vol. 14, no. 3, pp. 37–42, 2012.
ISNAD Gülcen, Burak et al. “Deneysel Karbon Tetraklorür Zehirlenmesinde Akciğer Doku Hasarı Ve Melatonin Hormonunun Koruyucu Rolü: Işık Mikroskobik Ve Biyokimyasal Bir Çalışma”. Duzce Medical Journal 14/3 (December 2012), 37-42.
JAMA Gülcen B, Kuş MA, Çolakoğlu S, Ögetürk M, Kuş İ, Ersoy MA, Karaca Ö. Deneysel Karbon Tetraklorür Zehirlenmesinde Akciğer Doku Hasarı ve Melatonin Hormonunun Koruyucu Rolü: Işık Mikroskobik ve Biyokimyasal Bir Çalışma. Duzce Med J. 2012;14:37–42.
MLA Gülcen, Burak et al. “Deneysel Karbon Tetraklorür Zehirlenmesinde Akciğer Doku Hasarı Ve Melatonin Hormonunun Koruyucu Rolü: Işık Mikroskobik Ve Biyokimyasal Bir Çalışma”. Duzce Medical Journal, vol. 14, no. 3, 2012, pp. 37-42.
Vancouver Gülcen B, Kuş MA, Çolakoğlu S, Ögetürk M, Kuş İ, Ersoy MA, Karaca Ö. Deneysel Karbon Tetraklorür Zehirlenmesinde Akciğer Doku Hasarı ve Melatonin Hormonunun Koruyucu Rolü: Işık Mikroskobik ve Biyokimyasal Bir Çalışma. Duzce Med J. 2012;14(3):37-42.