Promotion of Lipid and Protein Oxidative Damage in Rat Brain by Ethylmalonic Acid
- 124 Downloads
High concentrations of ethylmalonic acid are found in tissues and biological fluids of patients affected by ethylmalonic encephalopathy, deficiency of short-chain acyl-CoA dehydrogenase activity and other illnesses characterized by developmental delay and neuromuscular symptoms. The pathophysiological mechanisms responsible for the brain damage in these patients are virtually unknown. Therefore, in the present work we investigated the in vitro effect of EMA on oxidative stress parameters in rat cerebral cortex. EMA significantly increased chemiluminescence and thiobarbituric acid-reactive species levels (lipoperoxidation), as well as carbonyl content and oxidation of sulfhydryl groups (protein oxidative damage) and DCFH. EMA also significantly decreased the levels of reduced glutathione (non-enzymatic antioxidant defenses). In contrast, nitrate and nitrite levels were not affected by this short organic acid. It is therefore presumed that oxidative stress may represent a pathomechanism involved in the pathophysiology of the neurologic symptoms manifested by patients affected by disorders in which EMA accumulates.
KeywordsReactive oxygen species Ethylmalonic acid SCAD deficiency Oxidative stress Rat brain
This work was supported by grants from CNPq, PRONEX II, FAPERGS, PROPESQ/UFRGS, and FINEP research grant Rede Instituto Brasileiro de Neurociência (IBN-Net) # 01.06.0842-00, Instituto Nacional de Ciência e Tecnologia para Excitotoxicidade e Neuroproteção (INCT-EM).
- 4.Gregersen N, Winter VS, Corydon MJ et al (1998) Identification of four new mutations in the short-chain acyl-CoA dehydrogenase gene in two patients: one of the variant alleles, 511C>T is present at an unexpectedly high frequency in the general population, as was the case for 625G>A, together conferring susceptibility to ethylmalonic aciduria. Hum Mol Gen 7:619–627CrossRefPubMedGoogle Scholar
- 32.Roe CR, Ding J (2001) Mitochondrial fatty acid oxidation disorders. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 1909–1963Google Scholar
- 51.Halliwell B, Gutteridge JMC (1999) Detection of free radicals and others reactive species: trapping and fingerprinting. In: Halliwell B, Gutteridge JMC (eds) Free radicals in biology and medicine. Oxford University Press, Oxford, pp 351–425Google Scholar
- 52.Halliwell B, Gutteridge JMC (2007) Ageing, nutrition, disease and therapy: a role for antioxidants? In: Halliwell B, Gutteridge JMC (eds) Free radicals in biology and medicine. Oxford University Press, Oxford, pp 614–677Google Scholar
- 56.Zolkipli Z, Lehotay DC, Robinson BH et al (2008) Lipid peroxidative stress in SCAD deficiency (SCADD) and response to antioxidants. J Inherit Metab Dis 31(1):37Google Scholar