Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism Sadık So ¨g ˘u ¨t a, * , S. Salih Zorog ˘lu b , Hu ¨seyin O ¨ zyurt c , H. Ramazan Yılmaz d , Fikret O ¨ zug ˘urlu c , Ercan Sivaslı e ,O ¨ zer Yetkin b , Medaim Yanık f , Hamdi Tutkun g , Haluk A. Savas ß g , Mehmet Tarakc ßıog ˘lu h ,O ¨ mer Akyol a a Department of Biochemistry, Faculty of Medicine, Ino ¨nu ¨ University, Pasakosku Mahallesi 11, Sok. O ¨ zkaracalar Apt. No: 42/4, Malatya 44200, Turkey b Department of Child and Adolescent Psychiatry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey c Department of Biochemistry, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey d Division of Biology, Science and Art Faculty, Ino ¨nu ¨ University, Malatya, Turkey e Department of Pediatrics, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey f Department of Psychiatry, Faculty of Medicine, Harran University, Sanlıurfa, Turkey g Department of Psychiatry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey h Department of Biochemistry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey Received 11 September 2002; received in revised form 15 February 2003; accepted 16 February 2003 Abstract Background: There is evidence that oxygen free radicals play an important role in the pathophysiology of many neuropsychiatric disorders. Although it has not been investigated yet, several recent studies proposed that nitric oxide (NO) and other parameters related to oxidative stress may have a pathophysiological role in autism. Methods: We assessed the changes in superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and thiobarbituric acid-reactive substances (TBARS) levels in plasma as well as NO levels in red blood cells (RBC) in patients with autism (n = 27) compared to age- and sex- matched normal controls (n = 30). Results: In the autistic group, increased RBC NO levels ( p < 0.0001) and plasma GSH-Px activity ( p < 0.0001) and unchanged plasma TBARS levels and SOD activity were detected. Conclusions: These findings 0009-8981/03/$ - see front matter D 2003 Published by Elsevier Science B.V. doi:10.1016/S0009-8981(03)00119-0 Abbreviations: AA, arachidonic acid; CARS, Childhood Autism Rating Scale; Cd, cadmium; CNS, central nervous system; eNOS, endothelial nitric oxide syntase; GSH, reduced glutathione; GSH-Px, glutathione peroxidase; H 2 O 2 , hydrogen peroxide; iNOS, inducible nitric oxide synthase; MDA, Malondialdehyde; NADPH, reduced nicotinamide adenine dinucleotide phosphate; NBT, nitroblue tetrazolium; NMDA, N-methyl-D-aspartate; nNOS, neuronal nitric oxide synthase; NO, nitric oxide; NO 2 À , nitrite; NO 3 À , nitrate; NOS, nitric oxide synthase; 1 O 2 , singlet oxygen; O 2 SÀ , superoxide anion radical; S OH, hydroxyl radical; ONOO À , peroxynitrite; PUFAs, polyunsaturated fatty acids; ROS, reactive oxygen species; – SH, thiol; – S – NO, nitroso-thiols; SOD, superoxide dismutase; TBA, thiobarbituric acid; TBARS, thiobarbituric acid-reactive substances; XO, xanthine oxidase. * Corresponding author. Fax: +90-422-341-0728. E-mail address: sadiksogut2@hotmail.com (S. So ¨g ˘u ¨t). www.elsevier.com/locate/clinchim Clinica Chimica Acta 331 (2003) 111 –117