Oxidative Stress and Total Antioxidant Capacity in Diabetic and Nondiabetic Acute Ischemic Stroke Patients

Abstract

Free radical formation is the pivotal mechanism of neuronal injury of ischemic and reperfused brain tissue. In healthy individuals, antioxidant activity counterbalances free radical production, but in the case of ischemia, the balance between reactive oxygen species and antioxidant activity is shifted toward free radicals, causing oxidative stress. The aim of this study is to assess total antioxidant capacity (TAC) and oxidative stress in diabetic and nondiabetic acute stroke patients with 2 different stroke subtypes: large and small vessel disease stroke. Sixty-five acute ischemic stroke patients (29 diabetic and 36 nondiabetic) and 20 age-matched healthy control subjects were recruited in the study. Plasma TAC and nitric oxide (NO) metabolite levels (nitrite and nitrate) were measured by enzyme-linked immunosorbent assay. The subtypes of stroke were defined according to Trial of Org 10172 in Acute Stroke Treatment criteria. The main findings of this study are that the TAC and NO levels were significantly higher in diabetic acute stroke patients than in nondiabetic patients and control cases (P < .001 and P < .001, respectively). The TAC and NO levels were higher also in nondiabetic stroke patients than in controls, but the difference did not reach any significance. No difference was found between NO and TAC levels in large and small vessel stroke subtypes of diabetic and nondiabetic patients. The authors conclude that oxidative stress and counterbalancing antioxidant capacity are more pronounced in diabetic acute stroke patients than in nondiabetic acute stroke patients.

Keywords

oxidative stress total antioxidant capacity nitric oxide ischemic stroke

References

Maxwell SR , Lip GY Reperfusion injury: a review of the pathophysiology, clinical manifestations and therapeutic options. Int J Cardiol. 1997 ;58:95-117.

Traystman RJ , Kirsch JR , Koehler RC Oxygen radical mechanisms of brain injury following ischemia and reperfusion. J Appl Physiol. 1991;71:1185-1195.

Yoshida S. , Inoh S. , Asano T. , et al. Effect of transient ischemia on free fatty acids and phospholipids in the gerbil brain. Lipid peroxidation as a possible cause of postischemic injury. J Neurosurg. 1980;53:323-331. 4.

Yamamoto M. , Shima T. , Uozumi T. , et al. A possible role of lipid peroxidation in cellular damages caused by cerebral ischemia and the protective effect of alpha-tocopherol administration . Stroke. 1983;14:977-982. 5.

Polidori MC , Frei B. , Cherubini A. , et al. Increased plasma levels of lipid hydroperoxides in patients with ischemic stroke. Free Radic Biol Med. 1998;25:561-567. 6.

Loscalzo J. Nitric oxide and vascular disease. N Engl J Med. 1995;333:251-253.

Rudic RD , Seesa WC Nitric oxide in endhotelial dysfunction and vascular remodeling: clinical correlates and experimental links. Am J Hum Genet. 1999;64: 673-677.

Szabo C. Multiple pathway of peroxynitrite cytotoxicity. Toxicol Lett . 2003;140-141:105-112.

Mattson MP , Duan W. , Pedersen WA , Culmsee C. Neurodegenerative disorders and ischemic brain diseases. Apoptosis. 2001;6:69-81.

10.

Kamada H. , Yu F. , Nito C. , Chan PH Influence of hyperglycemia on oxidative stress and matrix metalloproteinase-9 activation after focal cerebral ischemia/reperfusion in rats: relation to blood-brain barrier dysfunction. Stroke. 2007 ;38:1044-1049.

11.

Stöllberger C. , Exner I. , Finsterer J. , Slany J. , Steger C. Stroke in diabetic and non-diabetic patients: course and prognostic value of admission serum glucose. Ann Med. 2005;37:357-364.

12.

Adams HP Jr , Bendixen BH , Kappelle LJ , et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke . 1993;24:35-41.

13.

Seneş M. , Kazan N. , Coşkun O. , Zengi O. , Inan L. , Yücel D. Oxidative and nitrosative stress in acute ischaemic stroke. Ann Clin Biochem. 2007;44:43-47.

14.

Fassbender K. , Fatar M. , Ragoschke A. , et al. Subacute but not acute generation of nitric oxide in focal cerebral ischemia. Stroke. 2000;31:2208-2211.

15.

Zhang ZG , Chopp M. , Gautam S. , Zaloga RL , Schmidt HHW Upregulation of neuronal nitric oxide synthase and mRNA, and selective sparing of nitric oxide synthase-containing neurons after focal cerebral ischemia in rat. Brain Res. 1994;654:85-95.

16.

Gümüştaş K. , Güzeylı FM , Atükeren P. , et al. The effects of vitamin E on lipid peroxidation, nitric oxide production and superoxide dismutase expression in hyperglycemic rats with cerebral ischemia-reperfusion injury. Turk Neurosurg. 2007;17:78-82.

17.

Nanetti L. , Taffi R. , Vignini A. , et al. Reactive oxygen species plasmatic levels in ischemic stroke . Mol Cell Biochem. 2007;303:19-25.

18.

Rashid PA , Whitehurst A. , Lawson N. , Bath PM Plasma nitric oxide (nitrate/nitrite) levels in acute stroke and their relationship with severity and outcome. J Stroke Cerebrovasc Dis. 2003;12:82-87.

19.

Anderson RE , Tan WK , Martin HS , Meyer FB Effects of glucose and Pao2 modulation on cortical intracellular acidosis, NADH redox state, and infarction in the ischemic penumbra. Stroke. 1999;30:160-170.

20.

Scott JF , Robinson GM , French JM , O’Connell JE , Alberti KG , Gray CS Prevalence of admission hyperglycaemia across clinical subtypes of acute stroke . Lancet. 1999;353:376-377.

21.

Bruno A. , Kent TA , Coull BM , et al. Treatment of hyperglycemia in ischemic stroke (THIS): a randomized pilot trial. Stroke. 2008;39:384-389.

22.

Prior RL , Cao G. In vivo total antioxidant capacity: comparison of different analytical methods . Free Radic Biol Med. 1999;27:1173-1181.

23.

Gariballa SE , Hutchin TP , Sinclair AJ Antioxidant capacity after acute ischaemic stroke. QJM. 2002; 95:685-690.

24.

Cherubini A. , Polidori MC , Bregnocchi M. , et al. Antioxidant profile and early outcome in stroke patients. Stroke. 2000;31:2295-2300.

25.

Chang CY , Lai YC , Cheng TJ , Lau MT , Hu ML Plasma levels of antioxidant vitamins, selenium, total sulfhydryl groups and oxidative products in ischemic-stroke patients compared to matched controls in Taiwan. Free Radic Res. 1998;28:15-24.

26.

Leinonen JS , Ahonen JP , Lönnrot K. , et al. Low plasma antioxidant activity is associated with high lesion volume and neurological impairment in stroke. Stroke. 2000;31:33-39.