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The Effect of Melatonin Hormone on Formaldehyde-Induced Liver Injury: A Light Microscopic and Biochemical Study

Year 2008, Volume: 13 Issue: 2, 92 - 97, 01.04.2008

Abstract

Objectives: This study aimed to investigate histological and biochemical changes in the livers of formaldehyde exposed rats and possible effects of melatonin hormone on these changes. Materials and Methods: A total of 21 male Wistar-albino rats were divided into three equal groups. Control rats in Group I received 0.9% NaCl alone intraperitoneally (ip), rats in Group II were injected with 10% formaldehyde (10 mg/kg, ip) every other day and rats in Group III received melatonin (25 mg/kg, ip) plus formaldehyde. At the end of 14-day experimental period, all animals were decapitated. The liver tissue samples were processed histologically and analyzed under light microscope. Additionally, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), xanthine oxidase (XO), and malondialdehyde (MDA) levels in the liver tissue samples were determined. Results: SOD, GSH-Px, CAT, XO and MDA levels of formaldehyde exposed rats were significantly higher than those of the control group rats. However, these biochemical values of rats treated with melatonin plus formaldehyde were lower than the non-melatonin group. Light microscopic evaluation of liver tissue samples of formaldehyde-exposed rats revealed enlarged sinusoids filled with blood and mononuclear cell infiltration in the portal areas and around the central veins. In addition, some of the hepatocytes showed vacuolar degeneration, and some had a hyperchromatic nucleus. In PAS staining, the hepatocytes around the portal areas were PAS negative. The rats treated with melatonin plus formaldehyde had somewhat fewer histological changes induced by formaldehyde exposure. Conclusion: The liver damage caused by formaldehyde may be partially prevented by melatonin administration. ©2008, Firat University, Medical Faculty

References

  • Smith AE. Formaldehyde. Occup Med 1992: 42: 83-88.
  • Usanmaz SE, Akarsu ES, Vural N. Neurotoxic effects of acute and subacute formaldehyde exposures in mice. Envir Toxicol Pharmacol 2002: 11: 93-100.
  • Feron VJ, Till HP, de Vriger F, et al. Aldehydes: Occurrence carcinogenic potential, mechanism of action and risk assessment. Mutat Res 1991: 259: 363-385.
  • Heck HD, Casanova M, Starr TB. Formaldehyde toxicity: New understanding. Crit Rev Toxicol 1990: 20: 397-426.
  • Sarnak MJ, Long J, King A. Intravesicular formaldehyde instillation and renal complications. Clin Nephrol 1999: 51: 122- 125.
  • Cohen BI, Pagnillo MK, Musikant BL, Deutsch AS. Formaldehyde evaluation from endodontic materials. Oral Health 1998: 88: 37-39.
  • Khamgaonkar MB, Fulare MB. Pulmonary effects of formaldehyde exposure: an environmental-epidemiological study. Indian J Chest Dis Allied Sci 1991: 33: 9-13.
  • Restani P, Galli CL. Oral toxicity of formaldehyde and its derivates. Crit Rev Toxicol 1991: 21: 315-328.
  • Taskinen H, Kyyrönen P, Hemminki K, et al. Laboratory work and pregnancy outcome. J Occup Med 1994: 36: 311-319.
  • Kilburn KH. Neurobehavioral impairment and seizures from formaldehyde. Arch of Environ Health 1994: 49: 37- 44.
  • Shizumi K, Sugita M, Yokote R, et al. Intestinal edema caused by ingested formalin. Chudoku Kenkyu 2003: 16: 447-451.
  • Kamata E, Nakadate M, Uchida O, et al. Results of a 28-month chronic inhalation toxicity study of formaldehyde in male Fisher- 344 rats. J Toxicol Sci 1997: 22: 239-254.
  • Rusch GM, Clary JJ, Rinehart WE, Bolte HF. A 26-week inhalation toxicity study with formaldehyde in the monkey, rat and hamster. Toxicol Appl Pharmacol 1983: 68: 329-343.
  • Dumont M, D’Hont C, Moreau A, et al. Retrograde injections of formaldehyde into the biliary tree induce alterations of biliary epithelial function in rats. Hepatology 1996: 24: 1217-1223.
  • Strubelt O, Younes M, Pentz R, Kuhnel W. Mechanistic study on formaldehyde-induced hepatotoxicity. J Toxicol Environ Health 1989: 27: 351-366.
  • Susko I, Mornjakovic Z, Alicelebic S, Cosovic E, Beganovic A. Retinal and pineal melatonin-from a circadian signal to therapeutic use. Med Arh 2004: 58: 61-64.
  • Vijayalaxmi, Reiter RJ, Tan DX, Herman TS, Thomas CR. Melatonin as a radioprotective agent: a review. Int J Radiat Oncol Biol Phys 2004: 59: 639- 653.
  • Hardeland R, Reiter RJ, Poeggeler B, Tan DX. The significance of the metabolism of the neurohormone melatonin: antioxidative protection and formation of bioactive substances. Neurosci Biobehav Rev 1993: 17: 347-357.
  • Lee PP, Pang SF. Melatonin and its receptors in the gastrointestinal tract. Biol Signals 1993: 2: 181-193.
  • Pang SF, Allen AE. Extra-pineal melatonin in the retina: Its regulation and physiological function. In: Reiter RJ (Editor). Pineal Research Review. New York, NY: Alan R. Liss., 1986: 55-95.
  • Stefulj J, Hortner M, Ghosh M, et al. Gene expression of the key enzymes of melatonin synthesis in extrapineal tissues of the rat. J Pineal Res 2001: 30: 243-247.
  • Csernus V, Mess B. Biorhythms and pineal gland. Neuro Endocrinol Lett 2003: 24: 404-411.
  • Kus I, Sarsilmaz M, Ogeturk M, et al. Ultrastructural interrelationship between the pineal gland and the testis in the male rat. Arch Androl 2000: 45: 119-124.
  • Guerrero JM, Reiter RJ. A brief survey of pineal gland-immune system interrelationships. Endocr Res 1992: 18: 91-113.
  • Longoni B, Salgo MG, Pryor WA, Marchiafava PL. Effects of melatonin on lipid peroxidation induced by oxygen radicals. Life Sci 1998: 62: 853-859.
  • Arendt J. Melatonin. Clin Endocrinol 1988: 29: 205-229.
  • 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 characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967: 70: 158-169.
  • Aebi H. Catalase. In: Bergmeyer U (Editor). Methods of Enzymatic Analysis. New York and London: Academic Press, 1974: 673-677.
  • Prajda N, Weber G. Malignant transformation-linked imbalance: decreased xanthine oxidase activity in hepatomas. FEBS Lett 1975: 59: 245-249.
  • Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hidroxynonenal. Methods Enzymol 1990: 186: 407-421.
  • Beall JR, Ulsamer AG. Formaldehyde and hepatotoxicity: a review. J Toxicol Environ Health 1984: 14: 1-21.
  • Husain K, Scott BR, Reddy SK, Somani SM. Chronic ethanol and nicotine interaction on rat tissue antioxidant defense system. Alcohol 2001: 25: 89-97.
  • Kamal AA, Gomaa A, el Khafif M, Hammad AS. Plasma lipid peroxides among workers exposed to silica or asbestos dusts. Environ Res 1990: 49: 173-180.
  • Dobrzynska I, Skrzydlewska E, Kasacka I, Figaszewski Z. Protective effect of N-acetylcysteine on rat liver cell membrane during methanol intoxication. J Pharm Pharmacol 2000: 52: 547- 552.
  • Tang M, Xie Y, Yi Y, Wang W. Effects of formaldehyde on germ cells of male mice. Wei Sheng Yan Jiu 2003: 32: 544-548.
  • Teng S, Beard K, Pourahmad J, et al. The formaldehyde metabolic detoxification enzyme systems and molecular cytotoxic mechanism in isolated rat hepatocytes. Chem Biol Interact 2001: 130-132: 285-296.
  • Skrzydlewska E, Farbiszewski R. Lipid peroxidation and antioxidant status in the liver, erythrocytes, and serum of rats after methanol intoxication. J Toxicol Environ Health A 1998: 53: 637-649.
  • Skrzydlewska E, Farbiszewski R. Liver and serum antioxidant status after methanol intoxication in rats. Acta Biochim Pol 1997: 44: 139-145.
  • Skrzydlewska E, Farbiszewski R. Decreased antioxidant defense mechanisms in rat liver after methanol intoxication. Free Radic Res 1997: 27: 369-375.
  • Datta NJ, Namasivayam A. In vitro effect of methanol on folate- deficient rat hepatocytes. Drug Alcohol Depend 2003: 71: 87-91.
  • Gupta YK, Gupta M, Kohli K. Neuroprotective role of melatonin in oxidative stress vulnerable brain. Indian J Physiol Pharmacol 2003: 47: 373-386.
  • Reiter RJ, Tan DX, Manchester LC, et al. Melatonin: detoxification of oxygen and nitrogen-based toxic reactants. Adv Exp Med Biol 2003: 527: 539-548.
  • Kabul Tarihi:23.01.2008

Melatonin Hormonunun Formaldehite Bağlı Karaciğer Hasarı Üzerine Etkisi: Işık Mikroskobik ve Biyokimyasal Bir Çalışma

Year 2008, Volume: 13 Issue: 2, 92 - 97, 01.04.2008

Abstract

Amaç: Bu çalışmada, formaldehite maruz bırakılan sıçanların karaciğerlerinde oluşan histolojik ve biyokimyasal değişiklikler ile melatonin hormonunun bu değişiklikler üzerine olası etkilerinin incelenmesi amaçlandı. Gereç ve Yöntem: Toplam 21 adet erkek Wistar-albino cinsi sıçan üç eşit gruba ayrıldı. Grup I'deki kontrol sıçanlara sadece % 0.9'luk NaCl intraperitoneal (ip) uygulanırken, grup II'deki sıçanlara % 10 formaldehit (10 mg/kg, ip) ve grup III'teki sıçanlara ise formaldehitin yanı sıra melatonin (25 mg/kg, ip) günaşırı olarak enjekte edildi. 14 günlük bir uygulama sürecinden sonra bütün hayvanlar dekapite edildi. Karaciğer doku örnekleri histolojik işlemlerden geçirilerek ışık mikroskop altında incelendi. Ek olarak, karaciğer doku örneklerinde süperoksit dismutaz (SOD), glutatyon peroksidaz (GSH-Px), katalaz (CAT), ksantin oksidaz (XO) ve malondialdehit (MDA) seviyeleri belirlendi. Bulgular: Formaldehite maruz bırakılan sıçanların SOD, GSH-Px, CAT, XO ve MDA seviyeleri kontrol değerlerinden anlamlı derecede yüksekti. Buna karşın, formaldehitle birlikte melatonin uygulanan sıçanların bu biyokimyasal değerleri melatonin uygulanmayan gruba nazaran düşüktü. Formaldehite maruz kalan sıçanların karaciğer doku örneklerinde gerçekleştirilen ışık mikroskobik değerlendirme, içi kan dolu sinüzoidler yanı sıra portal alanlar ve v.centralis civarında mononükleer hücre infiltrasyonunu açığa çıkardı. Ayrıca, hepatositlerin bazıları vakuoler dejenerasyon gösterirken, bazıları da hiperkromatik çekirdeğe sahipti. PAS boyamada, portal alanlara yakın hepatositler PAS negatifti. Melatonin ve formaldehitin birlikte uygulandığı sıçanlarda formaldehite bağlı histolojik değişiklikler nispeten daha az gözlendi. Sonuç: Formaldehitin neden olduğu karaciğer hasarı melatonin uygulamasıyla kısmen önlenebilir. ©2008, Fırat Üniversitesi, Tıp Fakültesi

References

  • Smith AE. Formaldehyde. Occup Med 1992: 42: 83-88.
  • Usanmaz SE, Akarsu ES, Vural N. Neurotoxic effects of acute and subacute formaldehyde exposures in mice. Envir Toxicol Pharmacol 2002: 11: 93-100.
  • Feron VJ, Till HP, de Vriger F, et al. Aldehydes: Occurrence carcinogenic potential, mechanism of action and risk assessment. Mutat Res 1991: 259: 363-385.
  • Heck HD, Casanova M, Starr TB. Formaldehyde toxicity: New understanding. Crit Rev Toxicol 1990: 20: 397-426.
  • Sarnak MJ, Long J, King A. Intravesicular formaldehyde instillation and renal complications. Clin Nephrol 1999: 51: 122- 125.
  • Cohen BI, Pagnillo MK, Musikant BL, Deutsch AS. Formaldehyde evaluation from endodontic materials. Oral Health 1998: 88: 37-39.
  • Khamgaonkar MB, Fulare MB. Pulmonary effects of formaldehyde exposure: an environmental-epidemiological study. Indian J Chest Dis Allied Sci 1991: 33: 9-13.
  • Restani P, Galli CL. Oral toxicity of formaldehyde and its derivates. Crit Rev Toxicol 1991: 21: 315-328.
  • Taskinen H, Kyyrönen P, Hemminki K, et al. Laboratory work and pregnancy outcome. J Occup Med 1994: 36: 311-319.
  • Kilburn KH. Neurobehavioral impairment and seizures from formaldehyde. Arch of Environ Health 1994: 49: 37- 44.
  • Shizumi K, Sugita M, Yokote R, et al. Intestinal edema caused by ingested formalin. Chudoku Kenkyu 2003: 16: 447-451.
  • Kamata E, Nakadate M, Uchida O, et al. Results of a 28-month chronic inhalation toxicity study of formaldehyde in male Fisher- 344 rats. J Toxicol Sci 1997: 22: 239-254.
  • Rusch GM, Clary JJ, Rinehart WE, Bolte HF. A 26-week inhalation toxicity study with formaldehyde in the monkey, rat and hamster. Toxicol Appl Pharmacol 1983: 68: 329-343.
  • Dumont M, D’Hont C, Moreau A, et al. Retrograde injections of formaldehyde into the biliary tree induce alterations of biliary epithelial function in rats. Hepatology 1996: 24: 1217-1223.
  • Strubelt O, Younes M, Pentz R, Kuhnel W. Mechanistic study on formaldehyde-induced hepatotoxicity. J Toxicol Environ Health 1989: 27: 351-366.
  • Susko I, Mornjakovic Z, Alicelebic S, Cosovic E, Beganovic A. Retinal and pineal melatonin-from a circadian signal to therapeutic use. Med Arh 2004: 58: 61-64.
  • Vijayalaxmi, Reiter RJ, Tan DX, Herman TS, Thomas CR. Melatonin as a radioprotective agent: a review. Int J Radiat Oncol Biol Phys 2004: 59: 639- 653.
  • Hardeland R, Reiter RJ, Poeggeler B, Tan DX. The significance of the metabolism of the neurohormone melatonin: antioxidative protection and formation of bioactive substances. Neurosci Biobehav Rev 1993: 17: 347-357.
  • Lee PP, Pang SF. Melatonin and its receptors in the gastrointestinal tract. Biol Signals 1993: 2: 181-193.
  • Pang SF, Allen AE. Extra-pineal melatonin in the retina: Its regulation and physiological function. In: Reiter RJ (Editor). Pineal Research Review. New York, NY: Alan R. Liss., 1986: 55-95.
  • Stefulj J, Hortner M, Ghosh M, et al. Gene expression of the key enzymes of melatonin synthesis in extrapineal tissues of the rat. J Pineal Res 2001: 30: 243-247.
  • Csernus V, Mess B. Biorhythms and pineal gland. Neuro Endocrinol Lett 2003: 24: 404-411.
  • Kus I, Sarsilmaz M, Ogeturk M, et al. Ultrastructural interrelationship between the pineal gland and the testis in the male rat. Arch Androl 2000: 45: 119-124.
  • Guerrero JM, Reiter RJ. A brief survey of pineal gland-immune system interrelationships. Endocr Res 1992: 18: 91-113.
  • Longoni B, Salgo MG, Pryor WA, Marchiafava PL. Effects of melatonin on lipid peroxidation induced by oxygen radicals. Life Sci 1998: 62: 853-859.
  • Arendt J. Melatonin. Clin Endocrinol 1988: 29: 205-229.
  • 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 characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967: 70: 158-169.
  • Aebi H. Catalase. In: Bergmeyer U (Editor). Methods of Enzymatic Analysis. New York and London: Academic Press, 1974: 673-677.
  • Prajda N, Weber G. Malignant transformation-linked imbalance: decreased xanthine oxidase activity in hepatomas. FEBS Lett 1975: 59: 245-249.
  • Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hidroxynonenal. Methods Enzymol 1990: 186: 407-421.
  • Beall JR, Ulsamer AG. Formaldehyde and hepatotoxicity: a review. J Toxicol Environ Health 1984: 14: 1-21.
  • Husain K, Scott BR, Reddy SK, Somani SM. Chronic ethanol and nicotine interaction on rat tissue antioxidant defense system. Alcohol 2001: 25: 89-97.
  • Kamal AA, Gomaa A, el Khafif M, Hammad AS. Plasma lipid peroxides among workers exposed to silica or asbestos dusts. Environ Res 1990: 49: 173-180.
  • Dobrzynska I, Skrzydlewska E, Kasacka I, Figaszewski Z. Protective effect of N-acetylcysteine on rat liver cell membrane during methanol intoxication. J Pharm Pharmacol 2000: 52: 547- 552.
  • Tang M, Xie Y, Yi Y, Wang W. Effects of formaldehyde on germ cells of male mice. Wei Sheng Yan Jiu 2003: 32: 544-548.
  • Teng S, Beard K, Pourahmad J, et al. The formaldehyde metabolic detoxification enzyme systems and molecular cytotoxic mechanism in isolated rat hepatocytes. Chem Biol Interact 2001: 130-132: 285-296.
  • Skrzydlewska E, Farbiszewski R. Lipid peroxidation and antioxidant status in the liver, erythrocytes, and serum of rats after methanol intoxication. J Toxicol Environ Health A 1998: 53: 637-649.
  • Skrzydlewska E, Farbiszewski R. Liver and serum antioxidant status after methanol intoxication in rats. Acta Biochim Pol 1997: 44: 139-145.
  • Skrzydlewska E, Farbiszewski R. Decreased antioxidant defense mechanisms in rat liver after methanol intoxication. Free Radic Res 1997: 27: 369-375.
  • Datta NJ, Namasivayam A. In vitro effect of methanol on folate- deficient rat hepatocytes. Drug Alcohol Depend 2003: 71: 87-91.
  • Gupta YK, Gupta M, Kohli K. Neuroprotective role of melatonin in oxidative stress vulnerable brain. Indian J Physiol Pharmacol 2003: 47: 373-386.
  • Reiter RJ, Tan DX, Manchester LC, et al. Melatonin: detoxification of oxygen and nitrogen-based toxic reactants. Adv Exp Med Biol 2003: 527: 539-548.
  • Kabul Tarihi:23.01.2008
There are 44 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Hıdır Pekmez This is me

Neriman Çolakoğlu Camcı This is me

İsmail Zararsız This is me

İlter Kus This is me

Murat Ögetürk This is me

Hacı Ramazan Yılmaz This is me

Mustafa Sarsılmaz This is me

Publication Date April 1, 2008
Published in Issue Year 2008 Volume: 13 Issue: 2

Cite

APA Pekmez, H., Camcı, N. Ç., Zararsız, İ., Kus, İ., et al. (2008). Melatonin Hormonunun Formaldehite Bağlı Karaciğer Hasarı Üzerine Etkisi: Işık Mikroskobik ve Biyokimyasal Bir Çalışma. Fırat Tıp Dergisi, 13(2), 92-97.
AMA Pekmez H, Camcı NÇ, Zararsız İ, Kus İ, Ögetürk M, Yılmaz HR, Sarsılmaz M. Melatonin Hormonunun Formaldehite Bağlı Karaciğer Hasarı Üzerine Etkisi: Işık Mikroskobik ve Biyokimyasal Bir Çalışma. Fırat Tıp Dergisi. April 2008;13(2):92-97.
Chicago Pekmez, Hıdır, Neriman Çolakoğlu Camcı, İsmail Zararsız, İlter Kus, Murat Ögetürk, Hacı Ramazan Yılmaz, and Mustafa Sarsılmaz. “Melatonin Hormonunun Formaldehite Bağlı Karaciğer Hasarı Üzerine Etkisi: Işık Mikroskobik Ve Biyokimyasal Bir Çalışma”. Fırat Tıp Dergisi 13, no. 2 (April 2008): 92-97.
EndNote Pekmez H, Camcı NÇ, Zararsız İ, Kus İ, Ögetürk M, Yılmaz HR, Sarsılmaz M (April 1, 2008) Melatonin Hormonunun Formaldehite Bağlı Karaciğer Hasarı Üzerine Etkisi: Işık Mikroskobik ve Biyokimyasal Bir Çalışma. Fırat Tıp Dergisi 13 2 92–97.
IEEE H. Pekmez, N. Ç. Camcı, İ. Zararsız, İ. Kus, M. Ögetürk, H. R. Yılmaz, and M. Sarsılmaz, “Melatonin Hormonunun Formaldehite Bağlı Karaciğer Hasarı Üzerine Etkisi: Işık Mikroskobik ve Biyokimyasal Bir Çalışma”, Fırat Tıp Dergisi, vol. 13, no. 2, pp. 92–97, 2008.
ISNAD Pekmez, Hıdır et al. “Melatonin Hormonunun Formaldehite Bağlı Karaciğer Hasarı Üzerine Etkisi: Işık Mikroskobik Ve Biyokimyasal Bir Çalışma”. Fırat Tıp Dergisi 13/2 (April 2008), 92-97.
JAMA Pekmez H, Camcı NÇ, Zararsız İ, Kus İ, Ögetürk M, Yılmaz HR, Sarsılmaz M. Melatonin Hormonunun Formaldehite Bağlı Karaciğer Hasarı Üzerine Etkisi: Işık Mikroskobik ve Biyokimyasal Bir Çalışma. Fırat Tıp Dergisi. 2008;13:92–97.
MLA Pekmez, Hıdır et al. “Melatonin Hormonunun Formaldehite Bağlı Karaciğer Hasarı Üzerine Etkisi: Işık Mikroskobik Ve Biyokimyasal Bir Çalışma”. Fırat Tıp Dergisi, vol. 13, no. 2, 2008, pp. 92-97.
Vancouver Pekmez H, Camcı NÇ, Zararsız İ, Kus İ, Ögetürk M, Yılmaz HR, Sarsılmaz M. Melatonin Hormonunun Formaldehite Bağlı Karaciğer Hasarı Üzerine Etkisi: Işık Mikroskobik ve Biyokimyasal Bir Çalışma. Fırat Tıp Dergisi. 2008;13(2):92-7.