Öz
In this study, we aimed to investigate cell death in liver and kidney cells of rats which were exposed to experimental copper toxicity. In the study, 56 adult, male, Sprague-Dawley rats were used. Two experimental groups with 14 rats in each and two separate control groups for the experimental groups were composed. During the experimental period, 75 mg/kg copper sulfate solution was orally administered to the rats in the first and the second experimental groups for 14 and 28 days, respectively. Blood–serum copper level was examined by Atomic Absorption Spectrophotometer. As a result, the serum copper level of the first experimental group is determined to be higher than both the second experimental group and the control groups. Histopathological results exhibit hepatocellular degeneration, portal mononuclear cell infiltration and necrotic hepatocytes at random locations in the liver of rats both from the first and the second experimental groups. Hepatocellular degeneration observed in the first experimental group was more severe, while the number of necrotic cells in the second experimental group was appeared to be higher. For both experimental groups, degeneration in corticomedullary tubus, renal cortex and focal lenfocyte infiltration were observed. TUNEL method and caspase -3, -8, -9 activities were examined immunohistochemically were used to show apoptosis. The examination revealed that liver and renal cells of both experimental groups necrosis or apoptosis. When both organs were observed, it was seen that apoptotic cells were predominant in the first experimental group while necrotic cells were predominant in the second experimental group. From this observation, it was concluded as liver undergoes to apoptosis with both intrinsic and extrinsic routes in the first experimental group while kidney tends only to intrinsic route
Kaynakça
- Aburto EM, Cribb AE, Fuentealba IC, Ikede BO, Kibenge FSB, Markham F (2001): Morphological and biochemical assessment of the liver response to excess dietary copper in Fischer 344 rats. Can J Vet Res, 65, 97- 103.
- Chipuk JE, Green DR (2008): How do BCL-2 proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol, 18, 157-164.
- Fong RN, Gonzalez BPE, Fuentealba IC, Cherian MG (2004): Role of tumor necrosis factor-a in the development of spontaneous hepatic toxicity in Long-Evans Cinnamon rats. Toxicol Appl Pharm, 200, 121–130.
- Formigari A, Irato P, Santon A (2007): Zinc, antioxidant systems and metallothionein in metal mediated-apoptosis: Biochemical and cytochemical aspects. Comp Biochem Phys, 146, 443–459.
- Fuentealba IC, Haywood S, Trafford J (1987): Evaluation of histochemical methods for the detection of copper overload in rat liver. Liver, 7, 277-282.
- Fuentealba IC, Haywood S (1988): Cellular mechanisms of toxicity and tolerance in the copper-loaded rat. I. Ultrastructural changes in the liver. Liver, 8, 372-380.
- Fuentealba I, Haywood S, Foser J (1989): Cellular mechanisms of toxicity and tolerance in the copper copper- loaded rat. II. Pathogenesis of copper toxicity in the liver. Exp Mol Pathol, 50, 26-37.
- Fuentealba IC, Davis RW, Elmes ME, Jasani B, Haywood S (1993): Mechanisms of tolerance in the copper- loaded rat liver. Exp Mol Pathol, 59, 71-84.
- Geberding JL (2004): Toxicological profile for copper. U.S. Department of Health and Human Service. Atlanta, Georgia.
- Harada M, Sakisaka S, Yoshitake M, Shakadoh S, Gondoh K, Sata M, Tanikawa K (1993): Biliary copper excretion in acutely and chronically copper-loaded rats. Hepatology, 17, 111-117.
- Harris E (2003): Basic and clinical aspects of copper. Crit Rev Cl Lab Sci, 40, 547-586.
- Haywood S, Loughran M, Batt RM (1985): Copper toxicosis and tolerance in the rat. III. intracellular localization of copper in the liver and kidney. Exp Mol Pathol, 43, 209-219.
- Kannan K, Jain S (2000): Oxidative stres and apoptosis. Pathophysiol, 7, 153-163.
- Karagül H, Altıntaş A, Fidancı UR, Sel T (2000): Klinik Biyokimya. 1. Baskı, Medisan Yayınevi, Ankara.
- Kaya S, Pirinçci İ, Bilgili A (2002): Veteriner Hekimliğinde Toksikoloji. 2.Baskı, Medisan Yayınevi, Ankara.
- Ke B, Llanos RML, Mercer JFB (2008): ATP7A transgenic and nontransgenic mice are resistant to high copper exposure. J Nut, 138, 693–697.
- Kerr JFR, Wyllie AH, Currie AR (1972): Apoptosis: a basic biological phenomenon with wideranging implications in tissue kinetics. Brit J Cancer, 26, 239-257.
- Langner C, Denk H (2004): Wilson Disease. Virchows Arch, 445, 111-118.
- Linder MC, Hazegh-Azam M (1996): Copper biochemistry and molecular biology. Am J Clin Nutr, 63, 797-811.
- Lutsenko S, Barnes NL, Bartee MY, Dmitriev OY (2007): Function and Regulation of Human Copper- Transporting ATPases. Physiol Rev, 87, 1011–1046.
- Metzstein MM, Stanfield GM, Horvitz HR (1998): Genetics of programmed cell death in C. elegans: past, present and future. Trends Genet, 14, 410-416.
- Mirkes PE (2002): 2001 Warkany lecture: to die or not to die, the role of apoptosis in normal and abnormal mammalian development. Teratology, 65, 228–239.
- Pourahmad J, Ross SJ, O’Brien P (2001): Lysosomal involvement in hepatocyte cytotoxicity induced by Cu but not Cd. Free Radical Bio Med, 30, 89–97.
- Pourahmad J, O’Brien P, Jokar F, Daraei B (2003): Carcinogenic metal induced sites of reactive oxygen species formation in hepatocytes. Toxicol in Vitro, 17, 803-810.
- Pulido MD, Parrish AR (2003): Metal-induced apoptosis: mechanisms. Mutat Res, 533, 227-241.
- Rana SVS (2008): Metals and apoptosis: recent developements. J Trace Elem Med Biology, 22, 262-284.
- Richter C, Gogvadze V, Laffranchi R, Schlapbach R, Schweizer M, Suter M, Walter, P, Yaffee M (1995): Oxidants in mitochondria: from physiology to diseases. Biochim Biophys Acta, 1271, 67-74.
- Rossi L, Lombardo MF, Ciriolo MR, Rotilio G (2004): Mitochondrial dysfunction in neurodegenerative diseases associated with copper imbalance. Neurochem Res, 29, 493-504.
- Roy DN, Mandal S, Sen G, Biswas T (2009): Superoxide anion mediated mitochondrial dysfunction leads to hepatocyte apoptosis preferentially in the periportal region during copper toxicity in rats. Chem-Biol Interact, 182, 136–147.
- Sabolic I (2006): Common mechanisms in nephopathy induced by toxic metals. Nephron Physiol, 104, 107-114.
- Saris NE, Skulski IA (1991): Interaction of Cu+ with mitochondria. Acta Chem Scand, 45, 1042-1046.
- Sharp PA (2003): Ctr1 and its role in body copper homeostasis. Int J Biochem Cell Biol, 35, 288-291.
- Simon HU, Haj-Yehia A, Levi-Schaffer F (2000): Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis, 5, 415–418.
- Siraki AG, Pourahmad J, Chan TS, Khan S, O’Brien PJ (2002): Endogenous and endobiotic induced reactive oxygen species formation by isolated hepatocytes. Free Radical Bio Med, 32, 2–10.
- Sokol RJ, Devereaux M, Mierau GW, Hambidge KM, Shikes RH (1990): Oxidant injury to hepatic mitochondrial lipids in rats with dietary copper overload. Modification by vitamin E deficiency. Gastroenterology, 99, 1061-1071.
- Tapiero H, Townsend DM, Tew KD (2003): Trace elements in human physiology and pathology, Copper. Biomed Pharmacother, 57, 386-398.
- Vermeulen K, Van Bockstaele DR, Berneman ZN (2005): Apoptosis: mechanisms and relevance in cancer. Ann Hematol, 84, 627–639.
Öz
Bu çalışmada deneysel olarak bakır zehirlenmesi oluşturulan sıçanların karaciğer ve böbrek hücrelerinde hücre ölümünün araştırılması amaçlandı. Çalışmada 56 adet erkek, erişkin, Sprague-Dawley ırkı sıçan kullanıldı. Her grupta 14 adet sıçan olmak üzere iki deneme ve deneme grupları için ayrı ayrı iki kontrol grubu oluşturuldu. Bakır sülfat solüsyonu I. deneme grubundaki sıçanlara günlük 75 mg/kg dozda ve 14 gün süreyle, II. deneme grubundakilere ise aynı dozda 28 gün süreyle gastrik sonda ile uygulandı. Atomik Absorbsiyon Spektrofotometresi ile kan- serum bakır düzeyi incelendi. I. deneme grubunda serum bakır düzeyinin II. grup ve kontrol gruplarına göre daha yüksek olduğu belirlendi. Histopatolojik incelemede, hepatosellüler dejenerasyon, portal mononükleer hücre infiltrasyonu ve hepatositlerde nekroza rastlandı. I. deneme grubunda hepatosellüler dejenerasyonun daha şiddetli, II. deneme grubunda ise nekrotik hücrelerin sayısının daha fazla olduğu dikkati çekti.Her iki deneme grubunda böbreklerde korteks ve kortikomedullar bölgedeki tubuluslarda dejenerasyon ve fokal lenfosit infiltrasyonu görüldü. Apoptozisi göstermek için TUNEL yöntemi ve kaspaz -3, -8, -9 aktiviteleri immunohistokimyasal olarak incelendi. Sonuçta her iki deneme grubunda karaciğer ve böbrekte hücrelerin hem apoptozis hem de nekroz ile ölebildiği, ancak her iki organda da I. deneme grubunda apoptotik hücrelerin, II. deneme grubunda nekrotik hücrelerin sayısının daha fazla olduğu görüldü. I. deneme grubunda hepatositlerin hem içsel hem de dışsal yollarla apoptozise uğrarken, böbrek tubulus epitellerinin içsel yolu kullandığı sonucuna varıldı
Kaynakça
- Aburto EM, Cribb AE, Fuentealba IC, Ikede BO, Kibenge FSB, Markham F (2001): Morphological and biochemical assessment of the liver response to excess dietary copper in Fischer 344 rats. Can J Vet Res, 65, 97- 103.
- Chipuk JE, Green DR (2008): How do BCL-2 proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol, 18, 157-164.
- Fong RN, Gonzalez BPE, Fuentealba IC, Cherian MG (2004): Role of tumor necrosis factor-a in the development of spontaneous hepatic toxicity in Long-Evans Cinnamon rats. Toxicol Appl Pharm, 200, 121–130.
- Formigari A, Irato P, Santon A (2007): Zinc, antioxidant systems and metallothionein in metal mediated-apoptosis: Biochemical and cytochemical aspects. Comp Biochem Phys, 146, 443–459.
- Fuentealba IC, Haywood S, Trafford J (1987): Evaluation of histochemical methods for the detection of copper overload in rat liver. Liver, 7, 277-282.
- Fuentealba IC, Haywood S (1988): Cellular mechanisms of toxicity and tolerance in the copper-loaded rat. I. Ultrastructural changes in the liver. Liver, 8, 372-380.
- Fuentealba I, Haywood S, Foser J (1989): Cellular mechanisms of toxicity and tolerance in the copper copper- loaded rat. II. Pathogenesis of copper toxicity in the liver. Exp Mol Pathol, 50, 26-37.
- Fuentealba IC, Davis RW, Elmes ME, Jasani B, Haywood S (1993): Mechanisms of tolerance in the copper- loaded rat liver. Exp Mol Pathol, 59, 71-84.
- Geberding JL (2004): Toxicological profile for copper. U.S. Department of Health and Human Service. Atlanta, Georgia.
- Harada M, Sakisaka S, Yoshitake M, Shakadoh S, Gondoh K, Sata M, Tanikawa K (1993): Biliary copper excretion in acutely and chronically copper-loaded rats. Hepatology, 17, 111-117.
- Harris E (2003): Basic and clinical aspects of copper. Crit Rev Cl Lab Sci, 40, 547-586.
- Haywood S, Loughran M, Batt RM (1985): Copper toxicosis and tolerance in the rat. III. intracellular localization of copper in the liver and kidney. Exp Mol Pathol, 43, 209-219.
- Kannan K, Jain S (2000): Oxidative stres and apoptosis. Pathophysiol, 7, 153-163.
- Karagül H, Altıntaş A, Fidancı UR, Sel T (2000): Klinik Biyokimya. 1. Baskı, Medisan Yayınevi, Ankara.
- Kaya S, Pirinçci İ, Bilgili A (2002): Veteriner Hekimliğinde Toksikoloji. 2.Baskı, Medisan Yayınevi, Ankara.
- Ke B, Llanos RML, Mercer JFB (2008): ATP7A transgenic and nontransgenic mice are resistant to high copper exposure. J Nut, 138, 693–697.
- Kerr JFR, Wyllie AH, Currie AR (1972): Apoptosis: a basic biological phenomenon with wideranging implications in tissue kinetics. Brit J Cancer, 26, 239-257.
- Langner C, Denk H (2004): Wilson Disease. Virchows Arch, 445, 111-118.
- Linder MC, Hazegh-Azam M (1996): Copper biochemistry and molecular biology. Am J Clin Nutr, 63, 797-811.
- Lutsenko S, Barnes NL, Bartee MY, Dmitriev OY (2007): Function and Regulation of Human Copper- Transporting ATPases. Physiol Rev, 87, 1011–1046.
- Metzstein MM, Stanfield GM, Horvitz HR (1998): Genetics of programmed cell death in C. elegans: past, present and future. Trends Genet, 14, 410-416.
- Mirkes PE (2002): 2001 Warkany lecture: to die or not to die, the role of apoptosis in normal and abnormal mammalian development. Teratology, 65, 228–239.
- Pourahmad J, Ross SJ, O’Brien P (2001): Lysosomal involvement in hepatocyte cytotoxicity induced by Cu but not Cd. Free Radical Bio Med, 30, 89–97.
- Pourahmad J, O’Brien P, Jokar F, Daraei B (2003): Carcinogenic metal induced sites of reactive oxygen species formation in hepatocytes. Toxicol in Vitro, 17, 803-810.
- Pulido MD, Parrish AR (2003): Metal-induced apoptosis: mechanisms. Mutat Res, 533, 227-241.
- Rana SVS (2008): Metals and apoptosis: recent developements. J Trace Elem Med Biology, 22, 262-284.
- Richter C, Gogvadze V, Laffranchi R, Schlapbach R, Schweizer M, Suter M, Walter, P, Yaffee M (1995): Oxidants in mitochondria: from physiology to diseases. Biochim Biophys Acta, 1271, 67-74.
- Rossi L, Lombardo MF, Ciriolo MR, Rotilio G (2004): Mitochondrial dysfunction in neurodegenerative diseases associated with copper imbalance. Neurochem Res, 29, 493-504.
- Roy DN, Mandal S, Sen G, Biswas T (2009): Superoxide anion mediated mitochondrial dysfunction leads to hepatocyte apoptosis preferentially in the periportal region during copper toxicity in rats. Chem-Biol Interact, 182, 136–147.
- Sabolic I (2006): Common mechanisms in nephopathy induced by toxic metals. Nephron Physiol, 104, 107-114.
- Saris NE, Skulski IA (1991): Interaction of Cu+ with mitochondria. Acta Chem Scand, 45, 1042-1046.
- Sharp PA (2003): Ctr1 and its role in body copper homeostasis. Int J Biochem Cell Biol, 35, 288-291.
- Simon HU, Haj-Yehia A, Levi-Schaffer F (2000): Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis, 5, 415–418.
- Siraki AG, Pourahmad J, Chan TS, Khan S, O’Brien PJ (2002): Endogenous and endobiotic induced reactive oxygen species formation by isolated hepatocytes. Free Radical Bio Med, 32, 2–10.
- Sokol RJ, Devereaux M, Mierau GW, Hambidge KM, Shikes RH (1990): Oxidant injury to hepatic mitochondrial lipids in rats with dietary copper overload. Modification by vitamin E deficiency. Gastroenterology, 99, 1061-1071.
- Tapiero H, Townsend DM, Tew KD (2003): Trace elements in human physiology and pathology, Copper. Biomed Pharmacother, 57, 386-398.
- Vermeulen K, Van Bockstaele DR, Berneman ZN (2005): Apoptosis: mechanisms and relevance in cancer. Ann Hematol, 84, 627–639.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Veteriner Cerrahi |
| Diğer ID | JA53GY43JT |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Yayımlanma Tarihi | 1 Mart 2013 |
| Yayımlandığı Sayı | Yıl 2013Cilt: 60 Sayı: 1 |