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Published in: Journal of Endocrinological Investigation 9/2015

01-09-2015 | Original Article

The lung endothelin system: a potent therapeutic target with bosentan for the amelioration of lung alterations in a rat model of diabetes mellitus

Authors: A. Cayir, R. A. Ugan, A. Albayrak, D. Kose, E. Akpinar, Y. Cayir, H. T. Atmaca, Z. Bayraktutan, M. Kara

Published in: Journal of Endocrinological Investigation | Issue 9/2015

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Abstract

Purpose

The aim of this study is to show the effect of a new mechanism on endothelin (ET) receptors in the physiopathology of diabetes-related pulmonary injury. We tested the hypothesis that dual ET-1 receptor antagonism via bosentan can reverse diabetes-induced lung injury.

Methods

The rats (24 male) were separated into four groups: group 1 (HEALTHY): Control group; group 2 (DM): Streptozotocin 60 mg/kg (i.p.); group 3 (DM + BOS-1): Diabetes + bosentan 50 mg/kg per-os; group 4 (DM + BOS-2): Diabetes + bosentan 100 mg/kg per-os. The bosentan treatment was initiated immediately after the onset of STZ-induced diabetes and continued for 6 weeks.

Results

In the treatment group, SOD activity was significantly increased, although GSH and MDA levels and TNF-α and TGF-β gene expression were decreased. Bosentan 50 mg/kg and bosentan 100 mg/kg showed a significantly down-regulatory effect on ET-1, ET-A, and ET-B mRNA expression.

Conclusions

In conclusion, increased endothelin levels in the lung associated with diabetes may be one cause of endothelial dysfunction, cytokine increase, and oxidant/antioxidant imbalance in the pathogenesis of complications that may develop during diabetes. With its multiple effects, bosentan therapy may be an effective option against complications that may develop in association with diabetes.
Literature
1.
go back to reference Karalliedde J, Gnudi L (2014) Diabetes mellitus, a complex and heterogeneous disease, and the role of insulin resistance as a determinant of diabetic kidney disease. Nephrol Dial Transplant Off Publ Eur Dial Transplant Assoc Eur Renal Assoc. doi:10.1093/ndt/gfu405 Karalliedde J, Gnudi L (2014) Diabetes mellitus, a complex and heterogeneous disease, and the role of insulin resistance as a determinant of diabetic kidney disease. Nephrol Dial Transplant Off Publ Eur Dial Transplant Assoc Eur Renal Assoc. doi:10.​1093/​ndt/​gfu405
4.
go back to reference Simsek DG, Aycan Z, Ozen S, Cetinkaya S, Kara C, Abali S, Demir K, Tunc O, Ucakturk A, Asar G, Bas F, Cetinkaya E, Aydin M, Karaguzel G, Orbak Z, Siklar Z, Altincik A, Okten A, Ozkan B, Ocal G, Semiz S, Arslanoglu I, Evliyaoglu O, Bundak R, Darcan S (2013) Diabetes care, glycemic control, complications, and concomitant autoimmune diseases in children with type 1 diabetes in Turkey: a multicenter study. J Clin Res Pediatr Endocrinol 5(1):20–26. doi:10.4274/Jcrpe.893 PubMedCentralCrossRefPubMed Simsek DG, Aycan Z, Ozen S, Cetinkaya S, Kara C, Abali S, Demir K, Tunc O, Ucakturk A, Asar G, Bas F, Cetinkaya E, Aydin M, Karaguzel G, Orbak Z, Siklar Z, Altincik A, Okten A, Ozkan B, Ocal G, Semiz S, Arslanoglu I, Evliyaoglu O, Bundak R, Darcan S (2013) Diabetes care, glycemic control, complications, and concomitant autoimmune diseases in children with type 1 diabetes in Turkey: a multicenter study. J Clin Res Pediatr Endocrinol 5(1):20–26. doi:10.​4274/​Jcrpe.​893 PubMedCentralCrossRefPubMed
6.
go back to reference Genuth S, Eastman R, Kahn R, Klein R, Lachin J, Lebovitz H, Nathan D, Vinicor F (2003) Implications of the United kingdom prospective diabetes study. Diabetes Care 26(Suppl 1):S28–S32PubMed Genuth S, Eastman R, Kahn R, Klein R, Lachin J, Lebovitz H, Nathan D, Vinicor F (2003) Implications of the United kingdom prospective diabetes study. Diabetes Care 26(Suppl 1):S28–S32PubMed
7.
go back to reference Gilbert RE (2013) Endothelial loss and repair in the vascular complications of diabetes: pathogenetic mechanisms and therapeutic implications. Circ J 77(4):849–856CrossRefPubMed Gilbert RE (2013) Endothelial loss and repair in the vascular complications of diabetes: pathogenetic mechanisms and therapeutic implications. Circ J 77(4):849–856CrossRefPubMed
8.
go back to reference Genuth S (2006) Insights from the diabetes control and complications trial/epidemiology of diabetes interventions and complications study on the use of intensive glycemic treatment to reduce the risk of complications of type 1 diabetes. Endocr Pract 12(Suppl 1):34–41. doi:10.4158/EP.12.S1.34 CrossRefPubMed Genuth S (2006) Insights from the diabetes control and complications trial/epidemiology of diabetes interventions and complications study on the use of intensive glycemic treatment to reduce the risk of complications of type 1 diabetes. Endocr Pract 12(Suppl 1):34–41. doi:10.​4158/​EP.​12.​S1.​34 CrossRefPubMed
10.
go back to reference Popov D, Simionescu M (2001) Structural and transport property alterations of the lung capillary endothelium in diabetes. Ital J Anat Embryol 106(2 Suppl 1):405–412PubMed Popov D, Simionescu M (2001) Structural and transport property alterations of the lung capillary endothelium in diabetes. Ital J Anat Embryol 106(2 Suppl 1):405–412PubMed
11.
go back to reference Vojtkova J, Ciljakova M, Michnova Z, Turcan T (2012) Chronic complications of diabetes mellitus related to the respiratory system. Pediatr Endocrinol Diabetes Metab 18(3):112–115PubMed Vojtkova J, Ciljakova M, Michnova Z, Turcan T (2012) Chronic complications of diabetes mellitus related to the respiratory system. Pediatr Endocrinol Diabetes Metab 18(3):112–115PubMed
14.
go back to reference Kuziemski K, Specjalski K, Jassem E (2011) Diabetic pulmonary microangiopathy—fact or fiction? Endokrynol Pol 62(2):171–176PubMed Kuziemski K, Specjalski K, Jassem E (2011) Diabetic pulmonary microangiopathy—fact or fiction? Endokrynol Pol 62(2):171–176PubMed
16.
go back to reference Scano G, Filippelli M, Romagnoli I, Mancini M, Misuri G, Duranti R, Rosi E (2000) Hypoxic and hypercapnic breathlessness in patients with type I diabetes mellitus. Chest 117(4):960–967CrossRefPubMed Scano G, Filippelli M, Romagnoli I, Mancini M, Misuri G, Duranti R, Rosi E (2000) Hypoxic and hypercapnic breathlessness in patients with type I diabetes mellitus. Chest 117(4):960–967CrossRefPubMed
17.
go back to reference Galie N, Beghetti M, Gatzoulis MA, Granton J, Berger RMF, Lauer A, Chiossi E, Landzberg M, Invest B (2006) Bosentan therapy in patients with Eisenmenger syndrome—a multicenter, double-blind, randomized, placebo-controlled study. Circulation 114(1):48–54. doi:10.1161/Circulationaha.106.630715 CrossRefPubMed Galie N, Beghetti M, Gatzoulis MA, Granton J, Berger RMF, Lauer A, Chiossi E, Landzberg M, Invest B (2006) Bosentan therapy in patients with Eisenmenger syndrome—a multicenter, double-blind, randomized, placebo-controlled study. Circulation 114(1):48–54. doi:10.​1161/​Circulationaha.​106.​630715 CrossRefPubMed
18.
go back to reference Sitbon O, Gressin V, Speich R, Macdonald PS, Opravil M, Cooper DA, Fourme T, Humbert M, Delfraissy JF, Simonneau G (2004) Bosentan for the treatment of human immunodeficiency virus-associated pulmonary arterial hypertension. Am J Respir Crit Care Med 170(11):1212–1217. doi:10.1164/rccm.200404-445OC CrossRefPubMed Sitbon O, Gressin V, Speich R, Macdonald PS, Opravil M, Cooper DA, Fourme T, Humbert M, Delfraissy JF, Simonneau G (2004) Bosentan for the treatment of human immunodeficiency virus-associated pulmonary arterial hypertension. Am J Respir Crit Care Med 170(11):1212–1217. doi:10.​1164/​rccm.​200404-445OC CrossRefPubMed
20.
go back to reference Rafnsson A, Bohm F, Settergren M, Gonon A, Brismar K, Pernow J (2012) The endothelin receptor antagonist bosentan improves peripheral endothelial function in patients with type 2 diabetes mellitus and microalbuminuria: a randomised trial. Diabetologia 55(3):600–607. doi:10.1007/s00125-011-2415-y CrossRefPubMed Rafnsson A, Bohm F, Settergren M, Gonon A, Brismar K, Pernow J (2012) The endothelin receptor antagonist bosentan improves peripheral endothelial function in patients with type 2 diabetes mellitus and microalbuminuria: a randomised trial. Diabetologia 55(3):600–607. doi:10.​1007/​s00125-011-2415-y CrossRefPubMed
21.
go back to reference Hauber HP, Blaukovitsch M (2010) Current and future treatment options in idiopathic pulmonary fibrosis. Inflamm Allergy Drug Targets 9(3):158–172CrossRefPubMed Hauber HP, Blaukovitsch M (2010) Current and future treatment options in idiopathic pulmonary fibrosis. Inflamm Allergy Drug Targets 9(3):158–172CrossRefPubMed
22.
go back to reference Cosentino F, Luscher TF (1998) Endothelial dysfunction in diabetes mellitus. J Cardiovasc Pharmacol 32(Suppl 3):S54–S61PubMed Cosentino F, Luscher TF (1998) Endothelial dysfunction in diabetes mellitus. J Cardiovasc Pharmacol 32(Suppl 3):S54–S61PubMed
24.
go back to reference Eringa EC, Serne EH, Meijer RI, Schalkwijk CG, Houben AJ, Stehouwer CD, Smulders YM, van Hinsbergh VW (2013) Endothelial dysfunction in (pre)diabetes: characteristics, causative mechanisms and pathogenic role in type 2 diabetes. Rev Endocr Metab Disord 14(1):39–48. doi:10.1007/s11154-013-9239-7 CrossRefPubMed Eringa EC, Serne EH, Meijer RI, Schalkwijk CG, Houben AJ, Stehouwer CD, Smulders YM, van Hinsbergh VW (2013) Endothelial dysfunction in (pre)diabetes: characteristics, causative mechanisms and pathogenic role in type 2 diabetes. Rev Endocr Metab Disord 14(1):39–48. doi:10.​1007/​s11154-013-9239-7 CrossRefPubMed
25.
go back to reference Feener EP, King GL (2001) Endothelial dysfunction in diabetes mellitus: role in cardiovascular disease. Heart Fail Monit 1(3):74–82PubMed Feener EP, King GL (2001) Endothelial dysfunction in diabetes mellitus: role in cardiovascular disease. Heart Fail Monit 1(3):74–82PubMed
28.
go back to reference Arison RN, Ciaccio EI, Glitzer MS, Cassaro JA, Pruss MP (1967) Light and electron microscopy of lesions in rats rendered diabetic with streptozotocin. Diabetes 16(1):51–56CrossRefPubMed Arison RN, Ciaccio EI, Glitzer MS, Cassaro JA, Pruss MP (1967) Light and electron microscopy of lesions in rats rendered diabetic with streptozotocin. Diabetes 16(1):51–56CrossRefPubMed
30.
go back to reference de Souza LF, Barreto F, da Silva EG, Andrades ME, Guimaraes EL, Behr GA, Moreira JC, Bernard EA (2007) Regulation of LPS stimulated ROS production in peritoneal macrophages from alloxan-induced diabetic rats: involvement of high glucose and PPARgamma. Life Sci 81(2):153–159. doi:10.1016/j.lfs.2007.04.035 CrossRefPubMed de Souza LF, Barreto F, da Silva EG, Andrades ME, Guimaraes EL, Behr GA, Moreira JC, Bernard EA (2007) Regulation of LPS stimulated ROS production in peritoneal macrophages from alloxan-induced diabetic rats: involvement of high glucose and PPARgamma. Life Sci 81(2):153–159. doi:10.​1016/​j.​lfs.​2007.​04.​035 CrossRefPubMed
31.
go back to reference Ghorbani A, Omrani GR, Hadjzadeh MA, Varedi M (2013) Proinsulin C-peptide inhibits lipolysis in diabetic rat adipose tissue through phosphodiestrase-3B enzyme. Horm Metab Res 45(3):221–225. doi:10.1055/s-0032-1323764 PubMed Ghorbani A, Omrani GR, Hadjzadeh MA, Varedi M (2013) Proinsulin C-peptide inhibits lipolysis in diabetic rat adipose tissue through phosphodiestrase-3B enzyme. Horm Metab Res 45(3):221–225. doi:10.​1055/​s-0032-1323764 PubMed
32.
go back to reference Ghorbani A, Varedi M, Hadjzadeh MA, Omrani GH (2010) Type-1 diabetes induces depot-specific alterations in adipocyte diameter and mass of adipose tissues in the rat. Exp Clin Endocrinol Diabetes 118(7):442–448. doi:10.1055/s-0030-1247566 CrossRefPubMed Ghorbani A, Varedi M, Hadjzadeh MA, Omrani GH (2010) Type-1 diabetes induces depot-specific alterations in adipocyte diameter and mass of adipose tissues in the rat. Exp Clin Endocrinol Diabetes 118(7):442–448. doi:10.​1055/​s-0030-1247566 CrossRefPubMed
33.
go back to reference Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358CrossRefPubMed Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358CrossRefPubMed
34.
go back to reference Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25(1):192–205CrossRefPubMed Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25(1):192–205CrossRefPubMed
35.
go back to reference Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34(3):497–500PubMed Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34(3):497–500PubMed
37.
go back to reference Guerci B, Bohme P, Kearney-Schwartz A, Zannad F, Drouin P (2001) Endothelial dysfunction and type 2 diabetes. Part 2: altered endothelial function and the effects of treatments in type 2 diabetes mellitus. Diabetes Metab 27(4 Pt 1):436–447PubMed Guerci B, Bohme P, Kearney-Schwartz A, Zannad F, Drouin P (2001) Endothelial dysfunction and type 2 diabetes. Part 2: altered endothelial function and the effects of treatments in type 2 diabetes mellitus. Diabetes Metab 27(4 Pt 1):436–447PubMed
38.
go back to reference Sarman B, Toth M, Somogyi A (1998) Role of endothelin-1 in diabetes mellitus. Diabetes Metab Rev 14(2):171–175CrossRefPubMed Sarman B, Toth M, Somogyi A (1998) Role of endothelin-1 in diabetes mellitus. Diabetes Metab Rev 14(2):171–175CrossRefPubMed
43.
go back to reference Cardillo C, Campia U, Bryant MB, Panza JA (2002) Increased activity of endogenous endothelin in patients with type II diabetes mellitus. Circulation 106(14):1783–1787CrossRefPubMed Cardillo C, Campia U, Bryant MB, Panza JA (2002) Increased activity of endogenous endothelin in patients with type II diabetes mellitus. Circulation 106(14):1783–1787CrossRefPubMed
44.
go back to reference McAuley DF, Nugent AG, McGurk C, Maguire S, Hayes JR, Johnston GD (2000) Vasoconstriction to endogenous endothelin-1 is impaired in patients with Type II diabetes mellitus. Clin Sci 99(3):175–179. doi:10.1042/Cs20000005 CrossRefPubMed McAuley DF, Nugent AG, McGurk C, Maguire S, Hayes JR, Johnston GD (2000) Vasoconstriction to endogenous endothelin-1 is impaired in patients with Type II diabetes mellitus. Clin Sci 99(3):175–179. doi:10.​1042/​Cs20000005 CrossRefPubMed
45.
46.
go back to reference Climent B, Fernandez N, Sanz E, Sanchez A, Monge L, Garcia-Villalon AL, Dieguez G (2005) Enhanced response of pig coronary arteries to endothelin-1 after ischemia-reperfusion. Role of endothelin receptors, nitric oxide and prostanoids. Eur J Pharmacol 524(1–3):102–110. doi:10.1016/j.ejphar.2005.09.002 CrossRefPubMed Climent B, Fernandez N, Sanz E, Sanchez A, Monge L, Garcia-Villalon AL, Dieguez G (2005) Enhanced response of pig coronary arteries to endothelin-1 after ischemia-reperfusion. Role of endothelin receptors, nitric oxide and prostanoids. Eur J Pharmacol 524(1–3):102–110. doi:10.​1016/​j.​ejphar.​2005.​09.​002 CrossRefPubMed
48.
go back to reference Channick RN, Simonneau G, Sitbon O, Robbins IM, Frost A, Tapson VF, Badesch DB, Roux S, Rainisio M, Bodin F, Rubin LJ (2001) Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 358(9288):1119–1123. doi:10.1016/S0140-6736(01)06250-X CrossRefPubMed Channick RN, Simonneau G, Sitbon O, Robbins IM, Frost A, Tapson VF, Badesch DB, Roux S, Rainisio M, Bodin F, Rubin LJ (2001) Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 358(9288):1119–1123. doi:10.​1016/​S0140-6736(01)06250-X CrossRefPubMed
49.
50.
go back to reference Araz O, Demirci E, Yilmazel Ucar E, Calik M, Pulur D, Karaman A, Yayla M, Altun E, Halici Z, Akgun M (2013) Comparison of reducing effect on lung injury of dexamethasone and bosentan in acute lung injury: an experimental study. Multidiscip Respir Med 8(1):74. doi:10.1186/2049-6958-8-74 PubMedCentralCrossRefPubMed Araz O, Demirci E, Yilmazel Ucar E, Calik M, Pulur D, Karaman A, Yayla M, Altun E, Halici Z, Akgun M (2013) Comparison of reducing effect on lung injury of dexamethasone and bosentan in acute lung injury: an experimental study. Multidiscip Respir Med 8(1):74. doi:10.​1186/​2049-6958-8-74 PubMedCentralCrossRefPubMed
51.
go back to reference Galie N, Rubin L, Hoeper M, Jansa P, Al-Hiti H, Meyer G, Chiossi E, Kusic-Pajic A, Simonneau G (2008) Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet 371(9630):2093–2100. doi:10.1016/S0140-6736(08)60919-8 CrossRefPubMed Galie N, Rubin L, Hoeper M, Jansa P, Al-Hiti H, Meyer G, Chiossi E, Kusic-Pajic A, Simonneau G (2008) Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet 371(9630):2093–2100. doi:10.​1016/​S0140-6736(08)60919-8 CrossRefPubMed
54.
go back to reference Nishimura M, Obayashi H, Mizuta I, Hara H, Adachi T, Ohta M, Tegoshi H, Fukui M, Hasegawa G, Shigeta H, Kitagawa Y, Nakano K, Kaji R, Nakamura N (2003) TNF, TNF receptor type 1, and allograft inflammatory factor-1 gene polymorphisms in Japanese patients with type 1 diabetes. Hum Immunol 64(2):302–309CrossRefPubMed Nishimura M, Obayashi H, Mizuta I, Hara H, Adachi T, Ohta M, Tegoshi H, Fukui M, Hasegawa G, Shigeta H, Kitagawa Y, Nakano K, Kaji R, Nakamura N (2003) TNF, TNF receptor type 1, and allograft inflammatory factor-1 gene polymorphisms in Japanese patients with type 1 diabetes. Hum Immunol 64(2):302–309CrossRefPubMed
55.
go back to reference Gonzalez-Clemente JM, Mauricio D, Richart C, Broch M, Caixas A, Megia A, Gimenez-Palop O, Simon I, Martinez-Riquelme A, Gimenez-Perez G, Vendrell J (2005) Diabetic neuropathy is associated with activation of the TNF-alpha system in subjects with type 1 diabetes mellitus. Clin Endocrinol 63(5):525–529. doi:10.1111/j.1365-2265.2005.02376.x CrossRef Gonzalez-Clemente JM, Mauricio D, Richart C, Broch M, Caixas A, Megia A, Gimenez-Palop O, Simon I, Martinez-Riquelme A, Gimenez-Perez G, Vendrell J (2005) Diabetic neuropathy is associated with activation of the TNF-alpha system in subjects with type 1 diabetes mellitus. Clin Endocrinol 63(5):525–529. doi:10.​1111/​j.​1365-2265.​2005.​02376.​x CrossRef
56.
go back to reference Yoshida A, Yoshida S, Khalil AK, Ishibashi T, Inomata H (1998) Role of NF-kappa B-mediated interleukin-8 expression in intraocular neovascularization. Invest Ophthalmol Vis Sci 39(7):1097–1106PubMed Yoshida A, Yoshida S, Khalil AK, Ishibashi T, Inomata H (1998) Role of NF-kappa B-mediated interleukin-8 expression in intraocular neovascularization. Invest Ophthalmol Vis Sci 39(7):1097–1106PubMed
57.
go back to reference Gupta S, Gambhir JK, Kalra O, Gautam A, Shukla K, Mehndiratta M, Agarwal S, Shukla R (2013) Association of biomarkers of inflammation and oxidative stress with the risk of chronic kidney disease in Type 2 diabetes mellitus in North Indian population. J Diabetes Complications 27(6):548–552. doi:10.1016/j.jdiacomp.2013.07.005 CrossRefPubMed Gupta S, Gambhir JK, Kalra O, Gautam A, Shukla K, Mehndiratta M, Agarwal S, Shukla R (2013) Association of biomarkers of inflammation and oxidative stress with the risk of chronic kidney disease in Type 2 diabetes mellitus in North Indian population. J Diabetes Complications 27(6):548–552. doi:10.​1016/​j.​jdiacomp.​2013.​07.​005 CrossRefPubMed
58.
go back to reference Tahara A, Kurosaki E, Yokono M, Yamajuku D, Kihara R, Hayashizaki Y, Takasu T, Imamura M, Li Q, Tomiyama H, Kobayashi Y, Noda A, Sasamata M, Shibasaki M (2013) Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol 715(1–3):246–255. doi:10.1016/j.ejphar.2013.05.014 CrossRefPubMed Tahara A, Kurosaki E, Yokono M, Yamajuku D, Kihara R, Hayashizaki Y, Takasu T, Imamura M, Li Q, Tomiyama H, Kobayashi Y, Noda A, Sasamata M, Shibasaki M (2013) Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol 715(1–3):246–255. doi:10.​1016/​j.​ejphar.​2013.​05.​014 CrossRefPubMed
62.
63.
go back to reference El Gazaerly H, Elbardisey DM, Eltokhy HM, Teaama D (2013) Effect of transforming growth factor Beta 1 on wound healing in induced diabetic rats. Int J Health Sci (Qassim) 7(2):160–172CrossRef El Gazaerly H, Elbardisey DM, Eltokhy HM, Teaama D (2013) Effect of transforming growth factor Beta 1 on wound healing in induced diabetic rats. Int J Health Sci (Qassim) 7(2):160–172CrossRef
64.
go back to reference Sipal S, Halici Z, Kiki I, Polat B, Albayrak A, Albayrak F, Karakus E, Aksak S, Ozturk B, Gundogdu C (2012) Comparative study of three angiotensin II type 1 receptor antagonists in preventing liver fibrosis in diabetic rats: stereology, histopathology, and electron microscopy. J Mol Histol 43(6):723–735. doi:10.1007/s10735-012-9441-z CrossRefPubMed Sipal S, Halici Z, Kiki I, Polat B, Albayrak A, Albayrak F, Karakus E, Aksak S, Ozturk B, Gundogdu C (2012) Comparative study of three angiotensin II type 1 receptor antagonists in preventing liver fibrosis in diabetic rats: stereology, histopathology, and electron microscopy. J Mol Histol 43(6):723–735. doi:10.​1007/​s10735-012-9441-z CrossRefPubMed
71.
72.
go back to reference Pennathur S, Heinecke JW (2007) Oxidative stress and endothelial dysfunction in vascular disease. Curr Diab Rep 7(4):257–264CrossRefPubMed Pennathur S, Heinecke JW (2007) Oxidative stress and endothelial dysfunction in vascular disease. Curr Diab Rep 7(4):257–264CrossRefPubMed
73.
go back to reference Wen Y, Skidmore JC, Porter-Turner MM, Rea CA, Khokher MA, Singh BM (2002) Relationship of glycation, antioxidant status and oxidative stress to vascular endothelial damage in diabetes. Diabetes Obes Metab 4(5):305–308CrossRefPubMed Wen Y, Skidmore JC, Porter-Turner MM, Rea CA, Khokher MA, Singh BM (2002) Relationship of glycation, antioxidant status and oxidative stress to vascular endothelial damage in diabetes. Diabetes Obes Metab 4(5):305–308CrossRefPubMed
74.
go back to reference Uyanik A, Unal D, Uyanik MH, Halici Z, Odabasoglu F, Altunkaynak ZB, Cadirci E, Keles M, Gundogdu C, Suleyman H, Bayir Y, Albayrak M, Unal B (2010) The effects of polymicrobial sepsis with diabetes mellitus on kidney tissues in ovariectomized rats. Ren Fail 32(5):592–602. doi:10.3109/08860221003759478 CrossRefPubMed Uyanik A, Unal D, Uyanik MH, Halici Z, Odabasoglu F, Altunkaynak ZB, Cadirci E, Keles M, Gundogdu C, Suleyman H, Bayir Y, Albayrak M, Unal B (2010) The effects of polymicrobial sepsis with diabetes mellitus on kidney tissues in ovariectomized rats. Ren Fail 32(5):592–602. doi:10.​3109/​0886022100375947​8 CrossRefPubMed
75.
go back to reference Suys B, de Beeck LO, Rooman R, Kransfeld S, Heuten H, Goovaerts I, Vrints C, de Wolf D, Matthys D, Manuel-y-Keenoy B (2007) Impact of oxidative stress on the endothelial dysfunction of children and adolescents with type 1 diabetes mellitus: protection by superoxide dismutase? Pediatr Res 62(4):456–461. doi:10.1203/PDR.0b013e318142581a CrossRefPubMed Suys B, de Beeck LO, Rooman R, Kransfeld S, Heuten H, Goovaerts I, Vrints C, de Wolf D, Matthys D, Manuel-y-Keenoy B (2007) Impact of oxidative stress on the endothelial dysfunction of children and adolescents with type 1 diabetes mellitus: protection by superoxide dismutase? Pediatr Res 62(4):456–461. doi:10.​1203/​PDR.​0b013e318142581a​ CrossRefPubMed
77.
go back to reference Likidlilid A, Patchanans N, Poldee S, Peerapatdit T (2007) Glutathione and glutathione peroxidase in type 1 diabetic patients. J Med Assoc Thai 90(9):1759–1767PubMed Likidlilid A, Patchanans N, Poldee S, Peerapatdit T (2007) Glutathione and glutathione peroxidase in type 1 diabetic patients. J Med Assoc Thai 90(9):1759–1767PubMed
79.
80.
go back to reference Albayrak A, Uyanik MH, Odabasoglu F, Halici Z, Uyanik A, Bayir Y, Albayrak F, Albayrak Y, Polat B, Suleyman H (2011) The effects of diabetes and/or polymicrobial sepsis on the status of antioxidant enzymes and pro-inflammatory cytokines on heart, liver, and lung of ovariectomized rats. J Surg Res 169(1):67–75. doi:10.1016/j.jss.2009.09.055 CrossRefPubMed Albayrak A, Uyanik MH, Odabasoglu F, Halici Z, Uyanik A, Bayir Y, Albayrak F, Albayrak Y, Polat B, Suleyman H (2011) The effects of diabetes and/or polymicrobial sepsis on the status of antioxidant enzymes and pro-inflammatory cytokines on heart, liver, and lung of ovariectomized rats. J Surg Res 169(1):67–75. doi:10.​1016/​j.​jss.​2009.​09.​055 CrossRefPubMed
81.
go back to reference Nakhjavani M, Esteghamati A, Nowroozi S, Asgarani F, Rashidi A, Khalilzadeh O (2010) Type 2 diabetes mellitus duration: an independent predictor of serum malondialdehyde levels. Singapore Med J 51(7):582–585PubMed Nakhjavani M, Esteghamati A, Nowroozi S, Asgarani F, Rashidi A, Khalilzadeh O (2010) Type 2 diabetes mellitus duration: an independent predictor of serum malondialdehyde levels. Singapore Med J 51(7):582–585PubMed
82.
go back to reference Reis JS, Veloso CA, Volpe CM, Fernandes JS, Borges EA, Isoni CA, Dos Anjos PM, Nogueira-Machado JA (2012) Soluble RAGE and malondialdehyde in type 1 diabetes patients without chronic complications during the course of the disease. Diab Vasc Dis Res 9(4):309–314. doi:10.1177/1479164111436316 CrossRefPubMed Reis JS, Veloso CA, Volpe CM, Fernandes JS, Borges EA, Isoni CA, Dos Anjos PM, Nogueira-Machado JA (2012) Soluble RAGE and malondialdehyde in type 1 diabetes patients without chronic complications during the course of the disease. Diab Vasc Dis Res 9(4):309–314. doi:10.​1177/​1479164111436316​ CrossRefPubMed
83.
go back to reference Singh G, Sharma B, Jaggi AS, Singh N (2014) Efficacy of bosentan, a dual ETA and ETB endothelin receptor antagonist, in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats. Pharmacol Biochem Behav 124:27–35. doi:10.1016/j.pbb.2014.05.002 CrossRefPubMed Singh G, Sharma B, Jaggi AS, Singh N (2014) Efficacy of bosentan, a dual ETA and ETB endothelin receptor antagonist, in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats. Pharmacol Biochem Behav 124:27–35. doi:10.​1016/​j.​pbb.​2014.​05.​002 CrossRefPubMed
84.
go back to reference Jiang JH, Yuen V, Xiang H, McNeill JH (2006) Improvement in cardiac function of diabetic rats by bosentan is not associated with changes in the activation of PKC isoforms. Mol Cell Biochem 282(1–2):177–185. doi:10.1007/S11010-006-1926-1 CrossRefPubMed Jiang JH, Yuen V, Xiang H, McNeill JH (2006) Improvement in cardiac function of diabetic rats by bosentan is not associated with changes in the activation of PKC isoforms. Mol Cell Biochem 282(1–2):177–185. doi:10.​1007/​S11010-006-1926-1 CrossRefPubMed
85.
go back to reference Sachidanandam K, Portik-Dobos V, Kelly-Cobbs AI, Ergul A (2010) Dual endothelin receptor antagonism prevents remodeling of resistance arteries in diabetes. Can J Physiol Pharm 88(6):616–621. doi:10.1139/Y10-034 CrossRef Sachidanandam K, Portik-Dobos V, Kelly-Cobbs AI, Ergul A (2010) Dual endothelin receptor antagonism prevents remodeling of resistance arteries in diabetes. Can J Physiol Pharm 88(6):616–621. doi:10.​1139/​Y10-034 CrossRef
Metadata
Title
The lung endothelin system: a potent therapeutic target with bosentan for the amelioration of lung alterations in a rat model of diabetes mellitus
Authors
A. Cayir
R. A. Ugan
A. Albayrak
D. Kose
E. Akpinar
Y. Cayir
H. T. Atmaca
Z. Bayraktutan
M. Kara
Publication date
01-09-2015
Publisher
Springer International Publishing
Published in
Journal of Endocrinological Investigation / Issue 9/2015
Electronic ISSN: 1720-8386
DOI
https://doi.org/10.1007/s40618-015-0282-y

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