Editöre Mektup
Role of nitric oxide and oxidative stress in pathophysiology of liver injury in streptozotocin-induced type 1 diabetic rats
Öz
Type 1 diabetes mellitus (T1DM) is a severe chronic metabolic disorder characterized by hyperglycaemia because of the alterations in insulin secretion or its action. It is previously shown that hyperglycemia related oxidative stress (OS) and excessive nitric oxide (NO) production may cause severe complications in kidney and brain. In this report, it is aimed to investigate the cytotoxic effects of NO and to evaluate possible interaction with T1DM related hepatopathology. Expression levels of 8-hydroxy-2'deoxyguanosine (8-OHdG), endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), Cu/Zn superoxide dismutase (SOD1) and glutathione reductase (GR) were examined by immunohistochemistry in liver tissues. Results of the study revealed that levels of 8-OHdG (P<0.001), eNOS (P<0.001), eNOS (P<0.001), SOD1 (P<0.001) and GR (P<0.001) were remarkably higher in liver with T1DM than control. The most prominent finding of this study is the increased levels of 8-OHdG in the mostly hepatocyte cytoplasm. These results suggest an involvement of oxidative DNA damage and OS might play a pivotal role on hepatic degeneration and this is a novel insight of pathogenesis on the explanation of cellular processes in streptozotocin (STZ)-induced type 1 diabetic rats’liver. Furthermore, these results also suggested that STZ-induced hepatic pathology might have been augmented by the contribution of high NO expression mediated OS. Taken together, the results suggest NO related hepatic inflammation and degeneration closely implicated in pathophysiology of T1DM. The results also clearly indicated that OS plays an important role on hepatic pathology and OS biomarkers might indicate the progress of the T1DM
Anahtar Kelimeler
Hepatopathology nitric oxide oxidative stress type 1 diabetes mellitus
Kaynakça
- Asahi M, Fujii J, Suzuki K, et al. (1995): Inactivation of glutathione peroxidase by nitric oxide. Implication for cytotoxicity. J Biol Chem, 270, 21035-21039.
- Brookes PS, Salinas EP, Darley-Usmar K, et al. (2000): Concentration-dependent effects of nitric oxide on mitochondrial permeability transition and cytochrome c release. J Biol Chem, 275, 20474-20479.
- Brüne B (2003): Nitric oxide: NO apoptosis or turning it ON? Cell Death Differ, 10, 864-869.
- Brüne B, von Knethen A, Sandau KB (1999): Nitric oxide (NO): An effector of apoptosis. Cell Death Differ, 10, 969- 975.
- Calabrese V, Cornelius C, Leso V et al. (2012): Oxidative stress, glutathione status, sirtuin and cellular stress response in type 2 diabetes. Biochimica et Biophysica Acta, 5, 729-736.
- Chen T, Zamora R, Zuckerbraun B, et al. (2003): Role of nitric oxide in liver injury. Curr Mol Med, 6, 519-26.
- Corson MA, James NL, Latta SE, et al. (1996): Phosphorylation of endothelial nitric oxide synthase in response to fluid shear stress. Circ Res, 5, 984-991.
- Dinçel GC, Yıldırım S (2016): Overexpression of ADAMTS-13 and neuronal nitric oxide synthase relates with neuropathology in streptozotocin-induced type 1 diabetic rats. Int J Clin Exp Pathol, 9, 4761-4778
- Dinçel GC, Yıldırım S (2016): Increased expressions of eNOS and iNOS correlate with apoptosis of diabetic nephropathy in streptozotocin-induced type 1 diabetic rats. Kafkas Univ Vet Fak Derg, 22, 381-390
- Dinçel GC, Atmaca HT (2015): Nitric oxide production increases during Toxoplasma gondii encephalitis in mice. Exp Parasitol, 156, 104-112.
- Dinçel GC, Atmaca HT (2016): Increased expressions of ADAMTS-13 and apoptosis contribute to neuropathology during Neuropathology, 36, 211-226 encephalitis in mice.
- Dinçel GC, Kul O (2015): Increased expressions of ADAMTS-13, neuronal nitric oxide synthase, and neurofilament correlate with severity of neuropathology in border disease virus-infected small ruminants. PLoS One, 10, e0120005.
- Dinçel GC, Kul O (2015): eNOS and iNOS trigger apoptosis in the brains of sheep and goats naturally infected with the border disease virus. Histol Histopathol, 10, 1233- 1242.
- Dinçer Y, Akçay T, Alademir Z, et al. (2002): Assessment of DNA base oxidation and glutathione level in patients with type 2 diabetes. Mutat Res, 505, 75-81.
- Dobashi K, Pahan K, Chahal A, et al. (1997): Modulation of endogenous antioxidant enzymes by nitric oxide in rat C6 glial cells. J Neurochem, 68, 1896-1903.
- Edirisinghe I, Rahman I. (2010): Cigarette smoke- mediated oxidative stress, shear stress, and endothelial dysfunction: Role of VEGFR2. Ann N Y Acad Sci, 1203, 66-72.
- Frances DE, Ronco MT, Monti JA, et al. (2010): Hyperglycemia induces apoptosis in rat liver through the increase of hydroxyl radical: New insights into the insulin effect. J Endocrinol, 205, 187-200.
- Goth L (2000): Lipid and carbohydrate metabolism in acatalasemia. Clin Chem, 46, 564-566.
- Halliwell B (1999): Oxygen and nitrogen are pro- carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: Measurement, mechanism and the effects of nutrition. Mutat Res, 443, 37-52.
- Harrison SA (2006): Liver disease in patients with diabetes mellitus. J Clin Gastroenterol, 40, 68-76.
- Heneka MT, Loschmann PA, Gleichmann M, et al. (1998): Induction of nitric oxide synthase and nitric oxide- mediated apoptosis in neuronal PC12 cells after stimulation with tumor necrosis factor-alpha/lipopolysaccharide. J Neurochem, 71, 88-94.
- Hon WM, Lee KH, Khoo HE (2002): Nitric oxide in liver diseases: Friend, foe, or just passerby? Ann N Y Acad Sci, 962, 275-95.
- Hunt JV, Dean RT, Wolff SP (1988): Hydroxyl radical production and autoxidative glycosylation. Glucose autoxidation as the cause of protein damage in the experimental glycation model of diabetes mellitus and ageing. Biochem J, 256, 205-212.
- Hunt JV, Smith CCT, Wolff SP. (1990): Autoxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose. Diabetes, 39, 1420-1424.
- Ignarro LJ, Buga GM, Wood KS, et al. (1987): Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA, 84, 9265-9269.
- Kakkar R, Mantha SV, Radhi J, et al. (1998): Increased oxidative stress in rat liver and pancreas during progression of streptozotocin-induced diabetes. Clin Sci (Lond), 6, 623-632.
- Kemeny SF, Figueroa DS, Clyne AM (2013): Hypo- and hyperglycemia impair endothelial cell actin alignment and nitric oxide synthase activation in response shear stress. PLoS One, 8, e66176.
- Kon K, Ikejima K, Okumura K, et al. (2010): Diabetic KK-A(y) mice are highly susceptible to oxidative hepatocellular damage induced by acetaminophen. Am J Physiol Gastrointest Liver Physiol, 299, 329-337.
- Kumar A, Pant MC, Singh HS, et al. (2012): Determinants of oxidative stress and DNA damage (8- OhdG) in squamous cell carcinoma of head and neck. Indian J Cancer, 3, 309-315.
- Liu J, Hinkhouse MM, Sun W, et al. (2004): Redox regulation of pancreatic cancer cell growth: Role of glutathione peroxidase in the suppression of the malignant phenotype. Hum Gene Ther, 3, 239-250.
- Manna P, Das J, Ghosh J, et al. (2010): Contribution of type 1 diabetes to rat liver dysfunction and cellular damage via activation of NOS, PARP, IkappaBalpha/NF-kappaB, MAPKs, Prophylactic role of arjunolic acid. Free Radic Biol Med, 48, 1465-1484. pathways:
- Mariani E, Polidori MC, Cherubini A, et al. (2005): Oxidative stress in brain aging, neurodegenerative and vascular diseases: An overview. J Chromatogr B Analyt Technol, 1, 65-75.
- Maritim AC, Sanders RA, Watkins JB (2003): Diabetes, oxidative stress, and antioxidants: A review. J Biochem Mol Toxicol, 1, 24.
- Moriya R, Uehara T, Nomura Y (2000): Mechanism of nitric oxide induced apoptosis in human neuroblastoma SH- SY5Y cells. FEBS Lett, 484, 253-260.
- Nathan C (1992): Nitric oxide as a secretory product of mammalian cells. FASEB J, 6, 3051-3064.
- Negre-Salvayre A, Salvayre R, Aug´es N, et al. (2009): Hyperglycemia and glycation in diabetic complications. Antioxid Redox Signal, 12, 3071-3109.
- Pacher P, Beckman JS, Liaudet L (2007): Nitric oxide and peroxynitrite in health and disease. Physiol Rev, 87, 315-424.
- Poulson HE, Prieme H, Loft S (1998): Role of oxidative DNA damage in cancer initiation and promotion. Eur J Cancer Prev, 1, 9-16.
- Rahigude A, Bhutada P, Kaulaskar S, et al. (2012): Participation of antioxidant and cholinergic system in protective effect of naringenin against type-2 diabetes- induced memory dysfunction in rats. Neuroscience, 226, 62- 72.
- Rains JL, Jain SK (2011): Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med, 5, 567-575.
- Rouhanizadeh M, Takabe W, Ai L, et al. (2008): Monitoring oxidative stress in vascular endothelial cells in response to fluid shear stress: from biochemical analyses to micro- and nanotechnologies. Methods Enzymol, 441, 111- 150.
- Shull S, Heintz NH, Periasamy M, et al. (1991): Differential regulation of antioxidant enzymes in response to oxidants. J Biol Chem, 36, 24398-24403.
- Uday B, Dipak D, Ranajit BK (1990): Reactive oxygen species: Oxidative damage and pathogenesis. Curr Sci, 77, 658-666.
- Wang C, Li S, Shang DJ, et al. (2011): Antihyperglycemic and neuroprotective effects of one novel Cu-Zn SOD mimetic. Bioorg Med Chem Lett, 21, 4320-4324.
- Wang RN, Bouwens L, Klöppel G (1994): Beta-cell proliferation in normal and streptozotocin-treated newborn rats: Site, dynamics and capacity. Diabetologia, 11, 1088- 1096.
- Weydert CJ, Cullen JJ (2010): Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nat Protoc, 1, 51-66.
- Wiseman H, Halliwell (1996): Damage to DNA by reactive oxygen and nitrogen species: Role in inflammatory disease and progression to cancer. Biochem J, 313, 17-29.
- Yun-Zhong F, Sheng Y, Guoyao Wu (2002): Free radicals, antioxidants, and nutrition. Nutrition, 18, 872- 879. Geliş tarihi: 26.06.2016 / Kabul tarihi: 22.12.2016 Address for correspondence: Güngör Çağdaş DİNÇEL Aksaray University, Eskil Vocational School, Laboratory and Veterinary Health Program. 68800 Eskil/Aksaray, Turkey. e-mail: gcdincel@yahoo.com.tr
Streptozotosin ile tip 1 diyabet oluşturulan sıçanların karaciğerlerinde meydana gelen hasarlardanitrik oksit ve oksidatif stresin patofizyolojideki rolleri
Öz
Tip 1 diyabet (T1D), insülinin salgı veya görevlerinde anormalliklerle karakterize kronik metabolik bir hastalıktır. Daha önceleri diyabetik hayvanlarda, hiperglisemi ile tetiklenen oksidatif stres (OS) ve nitrik oksit (NO) seviyelerindeki patolojik yükselmelerin böbrek ve beyinde şiddetli komplikasyonlara neden olduğunu gösterdik. Bu çalışma NO’in sitotoksik etkisinin ve OS’in T1D ile ilişkili hepatopatolojilerde herhangi bir ilişkinin olup olmadığını tanımlamak için tasarlanmıştır. Bu amaçla 8-hidroksi-2'deoxyguanosine (8-OHdG), endotelyal nitrik oksit sentaz (eNOS), uyarılabilir nitrik oksit sentaz (iNOS), Cu/Zn süperoksit dismutaz (SOD1) ve glutatyon redüktaz (GR) immunoreaktiviteleri karaciğer dokusunda araştırıldı. Çalışmada, 8-OHdG (P<0.001), eNOS (P<0.001), eNOS (P<0.001), SOD1 (P<0.001) ve GR (P<0.001) immunoreaktivitelerinin T1D’li hayvanlara ait karaciğer dokularında, sağlıklı kontrol gruplara göre ciddi anlamda bir artışın olduğu tespit edildi. Bu çalışmada en önemli bulgu, 8-OHdG sunumlarının genelde sitoplazmada olduğudur. Bu sonuçlar STZ ile indüklenen karaciğer dejenerasyonlarında OS’in ana kaynağının patolojik düzeylerde üretilen NO olduğunu da gösterdi. Ayrıca, oksidatif DNA hasarı ve oksidatif stresin diyabete bağlı karaciğer dejenerasyonlarında çok önemli bir rol aldığı ve hücresel mekanizmaların ortaya konmasında anahtar görevi üstleneceği gösterildi. Bu bulgular birlikte ele alındığında, T1D’le ilişkili karaciğer patolojileri NO aracılı karaciğer yangıları ve dejenerasyonların önemli bir faktör olduğu görülmektedir. Ayrıca, bu çalışma OS’in karaciğer patofizyolojisinde görev aldığını ve OS belirleyicilerinin hastalığın takibinde önemli görevler alabileceğini gösterdi
Anahtar Kelimeler
Kaynakça
- Asahi M, Fujii J, Suzuki K, et al. (1995): Inactivation of glutathione peroxidase by nitric oxide. Implication for cytotoxicity. J Biol Chem, 270, 21035-21039.
- Brookes PS, Salinas EP, Darley-Usmar K, et al. (2000): Concentration-dependent effects of nitric oxide on mitochondrial permeability transition and cytochrome c release. J Biol Chem, 275, 20474-20479.
- Brüne B (2003): Nitric oxide: NO apoptosis or turning it ON? Cell Death Differ, 10, 864-869.
- Brüne B, von Knethen A, Sandau KB (1999): Nitric oxide (NO): An effector of apoptosis. Cell Death Differ, 10, 969- 975.
- Calabrese V, Cornelius C, Leso V et al. (2012): Oxidative stress, glutathione status, sirtuin and cellular stress response in type 2 diabetes. Biochimica et Biophysica Acta, 5, 729-736.
- Chen T, Zamora R, Zuckerbraun B, et al. (2003): Role of nitric oxide in liver injury. Curr Mol Med, 6, 519-26.
- Corson MA, James NL, Latta SE, et al. (1996): Phosphorylation of endothelial nitric oxide synthase in response to fluid shear stress. Circ Res, 5, 984-991.
- Dinçel GC, Yıldırım S (2016): Overexpression of ADAMTS-13 and neuronal nitric oxide synthase relates with neuropathology in streptozotocin-induced type 1 diabetic rats. Int J Clin Exp Pathol, 9, 4761-4778
- Dinçel GC, Yıldırım S (2016): Increased expressions of eNOS and iNOS correlate with apoptosis of diabetic nephropathy in streptozotocin-induced type 1 diabetic rats. Kafkas Univ Vet Fak Derg, 22, 381-390
- Dinçel GC, Atmaca HT (2015): Nitric oxide production increases during Toxoplasma gondii encephalitis in mice. Exp Parasitol, 156, 104-112.
- Dinçel GC, Atmaca HT (2016): Increased expressions of ADAMTS-13 and apoptosis contribute to neuropathology during Neuropathology, 36, 211-226 encephalitis in mice.
- Dinçel GC, Kul O (2015): Increased expressions of ADAMTS-13, neuronal nitric oxide synthase, and neurofilament correlate with severity of neuropathology in border disease virus-infected small ruminants. PLoS One, 10, e0120005.
- Dinçel GC, Kul O (2015): eNOS and iNOS trigger apoptosis in the brains of sheep and goats naturally infected with the border disease virus. Histol Histopathol, 10, 1233- 1242.
- Dinçer Y, Akçay T, Alademir Z, et al. (2002): Assessment of DNA base oxidation and glutathione level in patients with type 2 diabetes. Mutat Res, 505, 75-81.
- Dobashi K, Pahan K, Chahal A, et al. (1997): Modulation of endogenous antioxidant enzymes by nitric oxide in rat C6 glial cells. J Neurochem, 68, 1896-1903.
- Edirisinghe I, Rahman I. (2010): Cigarette smoke- mediated oxidative stress, shear stress, and endothelial dysfunction: Role of VEGFR2. Ann N Y Acad Sci, 1203, 66-72.
- Frances DE, Ronco MT, Monti JA, et al. (2010): Hyperglycemia induces apoptosis in rat liver through the increase of hydroxyl radical: New insights into the insulin effect. J Endocrinol, 205, 187-200.
- Goth L (2000): Lipid and carbohydrate metabolism in acatalasemia. Clin Chem, 46, 564-566.
- Halliwell B (1999): Oxygen and nitrogen are pro- carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: Measurement, mechanism and the effects of nutrition. Mutat Res, 443, 37-52.
- Harrison SA (2006): Liver disease in patients with diabetes mellitus. J Clin Gastroenterol, 40, 68-76.
- Heneka MT, Loschmann PA, Gleichmann M, et al. (1998): Induction of nitric oxide synthase and nitric oxide- mediated apoptosis in neuronal PC12 cells after stimulation with tumor necrosis factor-alpha/lipopolysaccharide. J Neurochem, 71, 88-94.
- Hon WM, Lee KH, Khoo HE (2002): Nitric oxide in liver diseases: Friend, foe, or just passerby? Ann N Y Acad Sci, 962, 275-95.
- Hunt JV, Dean RT, Wolff SP (1988): Hydroxyl radical production and autoxidative glycosylation. Glucose autoxidation as the cause of protein damage in the experimental glycation model of diabetes mellitus and ageing. Biochem J, 256, 205-212.
- Hunt JV, Smith CCT, Wolff SP. (1990): Autoxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose. Diabetes, 39, 1420-1424.
- Ignarro LJ, Buga GM, Wood KS, et al. (1987): Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA, 84, 9265-9269.
- Kakkar R, Mantha SV, Radhi J, et al. (1998): Increased oxidative stress in rat liver and pancreas during progression of streptozotocin-induced diabetes. Clin Sci (Lond), 6, 623-632.
- Kemeny SF, Figueroa DS, Clyne AM (2013): Hypo- and hyperglycemia impair endothelial cell actin alignment and nitric oxide synthase activation in response shear stress. PLoS One, 8, e66176.
- Kon K, Ikejima K, Okumura K, et al. (2010): Diabetic KK-A(y) mice are highly susceptible to oxidative hepatocellular damage induced by acetaminophen. Am J Physiol Gastrointest Liver Physiol, 299, 329-337.
- Kumar A, Pant MC, Singh HS, et al. (2012): Determinants of oxidative stress and DNA damage (8- OhdG) in squamous cell carcinoma of head and neck. Indian J Cancer, 3, 309-315.
- Liu J, Hinkhouse MM, Sun W, et al. (2004): Redox regulation of pancreatic cancer cell growth: Role of glutathione peroxidase in the suppression of the malignant phenotype. Hum Gene Ther, 3, 239-250.
- Manna P, Das J, Ghosh J, et al. (2010): Contribution of type 1 diabetes to rat liver dysfunction and cellular damage via activation of NOS, PARP, IkappaBalpha/NF-kappaB, MAPKs, Prophylactic role of arjunolic acid. Free Radic Biol Med, 48, 1465-1484. pathways:
- Mariani E, Polidori MC, Cherubini A, et al. (2005): Oxidative stress in brain aging, neurodegenerative and vascular diseases: An overview. J Chromatogr B Analyt Technol, 1, 65-75.
- Maritim AC, Sanders RA, Watkins JB (2003): Diabetes, oxidative stress, and antioxidants: A review. J Biochem Mol Toxicol, 1, 24.
- Moriya R, Uehara T, Nomura Y (2000): Mechanism of nitric oxide induced apoptosis in human neuroblastoma SH- SY5Y cells. FEBS Lett, 484, 253-260.
- Nathan C (1992): Nitric oxide as a secretory product of mammalian cells. FASEB J, 6, 3051-3064.
- Negre-Salvayre A, Salvayre R, Aug´es N, et al. (2009): Hyperglycemia and glycation in diabetic complications. Antioxid Redox Signal, 12, 3071-3109.
- Pacher P, Beckman JS, Liaudet L (2007): Nitric oxide and peroxynitrite in health and disease. Physiol Rev, 87, 315-424.
- Poulson HE, Prieme H, Loft S (1998): Role of oxidative DNA damage in cancer initiation and promotion. Eur J Cancer Prev, 1, 9-16.
- Rahigude A, Bhutada P, Kaulaskar S, et al. (2012): Participation of antioxidant and cholinergic system in protective effect of naringenin against type-2 diabetes- induced memory dysfunction in rats. Neuroscience, 226, 62- 72.
- Rains JL, Jain SK (2011): Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med, 5, 567-575.
- Rouhanizadeh M, Takabe W, Ai L, et al. (2008): Monitoring oxidative stress in vascular endothelial cells in response to fluid shear stress: from biochemical analyses to micro- and nanotechnologies. Methods Enzymol, 441, 111- 150.
- Shull S, Heintz NH, Periasamy M, et al. (1991): Differential regulation of antioxidant enzymes in response to oxidants. J Biol Chem, 36, 24398-24403.
- Uday B, Dipak D, Ranajit BK (1990): Reactive oxygen species: Oxidative damage and pathogenesis. Curr Sci, 77, 658-666.
- Wang C, Li S, Shang DJ, et al. (2011): Antihyperglycemic and neuroprotective effects of one novel Cu-Zn SOD mimetic. Bioorg Med Chem Lett, 21, 4320-4324.
- Wang RN, Bouwens L, Klöppel G (1994): Beta-cell proliferation in normal and streptozotocin-treated newborn rats: Site, dynamics and capacity. Diabetologia, 11, 1088- 1096.
- Weydert CJ, Cullen JJ (2010): Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nat Protoc, 1, 51-66.
- Wiseman H, Halliwell (1996): Damage to DNA by reactive oxygen and nitrogen species: Role in inflammatory disease and progression to cancer. Biochem J, 313, 17-29.
- Yun-Zhong F, Sheng Y, Guoyao Wu (2002): Free radicals, antioxidants, and nutrition. Nutrition, 18, 872- 879. Geliş tarihi: 26.06.2016 / Kabul tarihi: 22.12.2016 Address for correspondence: Güngör Çağdaş DİNÇEL Aksaray University, Eskil Vocational School, Laboratory and Veterinary Health Program. 68800 Eskil/Aksaray, Turkey. e-mail: gcdincel@yahoo.com.tr
Toplam 48 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Veteriner Cerrahi |
| Diğer ID | JA26TK26HA |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Yayımlanma Tarihi | 1 Mart 2018 |
| Yayımlandığı Sayı | Yıl 2018Cilt: 65 Sayı: 1 |