Effects of histidine and imidazolelactic acid on various parameters of the oxidative stress in cerebral cortex of young rats

Abstract Histidinemia is an inherited metabolic disorder caused by deficiency of histidase activity, which leads to tissue accumulation of histidine and its derivatives. Affected patients usually present with speech delay and mental retardation, although asymptomatic patients have been reported. Considering that the pathophysiology of the neurological dysfunction of histidinemia is not yet understood and since histidine has been considered a pro‐oxidant agent, in the present study we investigated the effect of histidine and one of its derivatives, l ‐β‐imidazolelactic acid, at concentrations ranging from 0.1 to 10 mM, on various parameters of oxidative stress in cerebral cortex of 30‐day‐old Wistar rats. Chemiluminescence, total radical‐trapping antioxidant potential (TRAP), thiobarbituric acid reactive substances (TBA‐RS), and the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH‐Px) were measured in tissue homogenates in the presence of l ‐histidine or l ‐β‐imidazolelactic acid. We observed that l ‐histidine provoked an increase of chemiluminescence and a reduction of TRAP at concentrations of 2.5 mM and higher, while TBA‐RS measurement, GSH‐Px, CAT and SOD activities were not affected. Furthermore, l ‐β‐imidazolelactic acid provoked antioxidant effects at high concentrations (5–10 mM) as observed by the reduction of chemiluminescence, although this compound enhanced chemiluminescence at low concentrations (0.5–1 mM). These results suggest that in vitro oxidative stress is elicited by histidine but only at supraphysiological concentrations.