Does ADMA affect the oxidant/antioxidant balance in rats?

Asymmetric dimethylarginine (ADMA) is an inhibitor of nitric oxide synthase (NOS). Oxidative stress might be defined as an imbalance between protein oxidation and antioxidants. Our aim was to determine in vivo whether ADMA causes oxidative damage. Materials and methods: Thirty rats were divided into 3 equal groups: a control group, a group administered 1 mg/kg ADMA, and a group administered 2 mg/kg ADMA. ADMA was administered intraperitoneally for 7 days. Malondialdehyde (MDA), protein carbonyl (PC) content, and nitrate+nitrite concentrations were measured with serum samples. Superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) activities were analyzed with plasma samples. Results: A significant increase in MDA concentration was observed in the ADMA groups, but this increase was not dose-dependent. However, no significant changes in PC content or nitrate+nitrite concentration were observed. Furthermore, catalase, SOD, and GSH-Px activity was suppressed in the ADMA groups. Suppression of GSH-Px activity was dose-dependent. Conclusion: ADMA results in oxidative damage in vivo with lower doses than in NOS inhibition. ADMA has more of an oxidative effect on lipids than it does on proteins. Antioxidant enzymes must be consumed in significant amounts to remove the stress produced by ADMA.

Does ADMA affect the oxidant/antioxidant balance in rats?

Asymmetric dimethylarginine (ADMA) is an inhibitor of nitric oxide synthase (NOS). Oxidative stress might be defined as an imbalance between protein oxidation and antioxidants. Our aim was to determine in vivo whether ADMA causes oxidative damage. Materials and methods: Thirty rats were divided into 3 equal groups: a control group, a group administered 1 mg/kg ADMA, and a group administered 2 mg/kg ADMA. ADMA was administered intraperitoneally for 7 days. Malondialdehyde (MDA), protein carbonyl (PC) content, and nitrate+nitrite concentrations were measured with serum samples. Superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) activities were analyzed with plasma samples. Results: A significant increase in MDA concentration was observed in the ADMA groups, but this increase was not dose-dependent. However, no significant changes in PC content or nitrate+nitrite concentration were observed. Furthermore, catalase, SOD, and GSH-Px activity was suppressed in the ADMA groups. Suppression of GSH-Px activity was dose-dependent. Conclusion: ADMA results in oxidative damage in vivo with lower doses than in NOS inhibition. ADMA has more of an oxidative effect on lipids than it does on proteins. Antioxidant enzymes must be consumed in significant amounts to remove the stress produced by ADMA.

___

  • Tran CT, Leiper JM, Vallance P. The DDAH/ADMA/NOS pathway. Atheroscler Suppl 2003; 4: 33–40.
  • Kökçam İ, Dertlioğlu SB. The levels of nitric oxide and metabolites in Behçet’s disease. Turk J Med Sci 2011; 41: 587–94. 6. Boger RH, Bode-Boger SM, Tsao PS, Lin PS, Chan JR, Cooke JP. An endogenous inhibitor of nitric oxide synthase regulates endothelial adhesiveness for monocytes. J Am Coll Cardiol 2000; 36: 2287–95.
  • Antoniades C, Shirodaria C, Crabtree M, Rinze R, Alp N, Cunnington C et al. Altered plasma versus vascular biopterins in human atherosclerosis reveal relationships between endothelial nitric oxide synthase coupling, endothelial function, and inflammation. Circulation 2007; 116: 2851–9.
  • Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 1996; 271: C1424–37.
  • Ducrocq C, Blanchard B, Pignatelli B, Ohshima H. Peroxynitrite: an endogenous oxidizing and nitrating agent. Cell Mol Life Sci 1999; 55: 1068–77.
  • Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 1991; 11: 81–128.
  • Leiper J, Murray-Rust J, McDonald N, Vallance P. S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase. Proc Natl Acad Sci USA 2002; 99: 13527–32.
  • MacAllister RJ, Parry H, Kimoto M, Ogawa T, Russell RJ, Hodson H et al. Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase. Br J Pharmacol 1996; 119: 1533–40.
  • Ito A, Tsao PS, Adimoolam S, Kimoto M, Ogawa T, Cooke JP. Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 1999; 99: 3092–5.
  • Noris M, Perico N, Remuzzi G. Mechanisms of disease: pre- eclampsia. Nat Clin Pract Nephrol 2005; 1: 98–114.
  • Evans P, Halliwell B. Free radicals and hearing. Cause, consequence, and criteria. Ann N Y Acad Sci 1999; 884: 19–40.
  • Cochrane CG. Cellular injury by oxidants. Am J Med 1991; 91: 23S–30S.
  • Draper HH, Hadley M. Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 1990; 186: 421– 31.
  • Packer L, Glazer NA. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 1990; 186: 464–79.
  • Cortas NK, Wakid NW. Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 1990; 36: 1440–3.
  • Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide-dismutase. Clin Chem 1988; 34: 497–500.
  • Durak I, Yurtarslanl Z, Canbolat O, Akyol O. A methodological approach to superoxide-dismutase (sod) activity assay based on inhibition of nitroblue tetrazolium (Nbt) reduction. Clin Chim Acta 1993; 214: 103–4.
  • Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967; 70: 158–69.
  • Aebi H, Wyss SR, Scherz B, Skvaril F. Heterogeneity of erythrocyte catalase II. Isolation and characterization of normal and variant erythrocyte catalase and their subunits. Eur J Biochem 1974; 48: 137–45.
  • Yang YY, Lee TY, Huang YT, Chan CC, Yeh YC, Lee FY et al. Asymmetric dimethylarginine (ADMA) determines the improvement of hepatic endothelial dysfunction by vitamin E in cirrhotic rats. Liver Int 2012; 32: 48–57.
  • Tain YL, Kao YH, Hsieh CS, Chen CC, Sheen JM, Lin IC et al. Melatonin blocks oxidative stress-induced increased asymmetric dimethylarginine. Free Radic Biol Med 2010; 49: 1088–98.
  • Chen Y, Xu X, Sheng M, Zhang X, Gu Q, Zheng Z. PRMT-1 and DDAHs-induced ADMA upregulation is involved in ROS- and RAS-mediated diabetic retinopathy. Exp Eye Res 2009; 89: 1028–34.
  • Wells SM, Holian A. Asymmetric dimethylarginine induces oxidative and nitrosative stress in murine lung epithelial cells. Am J Respir Cell Mol Biol 2007; 36: 520–8.
  • Channon KM, Guzik TJ. Mechanisms of superoxide production in human blood vessels: relationship to endothelial dysfunction, clinical and genetic risk factors. J Physiol Pharmacol 2002; 53: 515–24.
  • Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases - The role of oxidant stress. Circulation Research 2000; 87: 840–4.
  • Nair J, Ohshima H, Nair UJ, Bartsch H. Endogenous formation of nitrosamines and oxidative DNA-damaging agents in tobacco users. Crit Rev Toxicol 1996; 26: 149–61.
  • Ardanaz N, Pagano PJ. Hydrogen peroxide as a paracrine vascular mediator: regulation and signaling leading to dysfunction. Exp Biol Med 2006; 231: 237–51.
  • Cao C, Edwards A, Sendeski M, Lee-Kwon W, Cui L, Cai CY et al. Intrinsic nitric oxide and superoxide production regulates descending vasa recta contraction. Am J Physiol Renal Physiol 2010; 299: F1056–64.
  • Sharma M, Zhou Z, Miura H, Papapetropoulos A, McCarthy ET, Sharma R et al. ADMA injures the glomerular filtration barrier: role of nitric oxide and superoxide. Am J Physiol Renal Physiol 2009; 296: F1386–95.
  • Yang ZC, Wang KS, Wu Y, Zou XQ, Xiang YY, Chen XP et al. Asymmetric dimethylarginine impairs glucose utilization via ROS/TLR4 pathway in adipocytes: an effect prevented by vitamin E. Cell Physiol Biochem 2009; 24: 115–24.
  • Mehmetoğlu İ, Kurban S. Effects of two different doses of acetylsalicylic acid on serum nitric oxide, asymmetric dimethylarginine, and homocysteine levels in healthy volunteers. Turk J Med Sci 2012; 42: 269–74.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

Hepatitis G virus and its prevalence and genotypes in patients with hepatitis B and C in Ahvaz, southwestern Iran

Javanmard DAVOD, Makvandi MANOOCHEHR, Hajiani ESKANDAR, Khalafkhany DAVOD, Samarbaf Zadeh REZA ALI

Rapid identification of Aeromonas species in stool samples with chromogenic media and matrix-assisted laser desorption ionization time of flight mass spectrometry: an institutional experience

Işın AKYAR, Simge CAN

The in vitro determination of genotoxicity in peripheral lymphocytes of welders exposed to fumes from metal arc welding

Ceylan ŞENER, Halil Erhan EROĞLU

Measurement of the in-air output ratio for high-energy photon beams used in radiotherapy

Murugan APPASAMY, Sidonia Valas XAVIER, Thayalan KUPPUSAMY, Ramasubramanian VELAYUDHAM

JAK2 V617F mutation in Iranian patients with myeloproliferative neoplasms: clinical and laboratory findings

Behzad POOPAK, Majid FARSHDOUSTI HAGH, Najmaldin SAKI, Fazel ELAHI, Hamid REZVANI, Gelareh KHOSRAVIPOUR, Mohammad Ali JAHANGIRPOUR, Shirin BOLOURI, Tolou GOLKAR, Parviz FALAH

An alternative method of oral to nasal endotracheal intubation in patients undergoing maxillofacial surgery

Nurdan BEDİRLİ, Gökçen EMMEZ, Cengiz Bekir DEMİREL, Metin ALKAN, Hasan Kutluk PAMPAL

Effect of the presence of pneumonia on noninvasive ventilation success in chronic obstructive pulmonary disease cases with acute hypercapnic respiratory failure

Serdar AKPINAR, Kazım ROLLAS, Evrim Eylem AKPINAR, Ali ALAGÖZ, Nazire UÇAR, Yusuf Tuğrul ŞİPİT

Is renal cell cancer stage migration valid throughout the world?

Emin Yener GÜLTEKİN, Esin YILDIZ, Semih AYAN, Esat KORĞALI, Hüseyin SAYGIN, Ziynet ÇINAR, Gökhan GÖKÇE

Effects of ethyl pyruvate administration on female rats’ pyramidal cells of cornu ammonis after brain ischemia: a stereological and histopathological study

Ayşe İKİNCİ, Ersan ODACI, Orhan BAŞ

Rapid identification of Aeromonas species in stool samples with chromogenic media and matrix-assisted laser desorption ionization-time of flight mass spectrometry: an institutional experience

Işın AKYAR, Simge CAN