Guanidinoacetate Decreases Antioxidant Defenses and Total Protein Sulfhydryl Content in Striatum of Rats

Abstract

Guanidinoacetate methyltransferase (GAMT) deficiency is an inherited neurometabolic disorder biochemically characterized by tissue accumulation of guanidinoacetate (GAA) and depletion of creatine. Affected patients present epilepsy and mental retardation whose pathogeny is unclear. In the present study we investigated the in vitro and in vivo (intrastriatal administration) effects of GAA on some oxidative stress parameters in rat striatum. Sixty-day-old rats were used for intrastriatal infusion of GAA. For the in vitro studies, 60-day-old Wistar rats were killed by decapitation and the striatum was pre-incubated for 1 h at 37 degrees C in the presence of GAA at final concentrations ranging from 10 to 100 microM. Parameters of oxidative stress such as total radical-trapping antioxidant potential (TRAP), antioxidant enzymes (SOD, GPx, and CAT), protein carbonyl and thiol contents were measured. DNA damage was also evaluated. Results showed that GAA administration (in vivo studies) or the addition of 100 microM GAA to assays (in vitro studies) significantly decreased TRAP, SOD activity, and total thiol levels in rat striatum. In contrast, this guanidino compound did not alter protein carbonyl content and the activities of CAT and GPx. DNA damage was not found after intrastriatal administration of GAA. The data indicate that the metabolite accumulating in GAMT deficiency decreases antioxidant capacity and total thiol content in the striatum. It is therefore presumed that this pathomechanism may contribute at least in part to the pathophysiology of the brain injury observed in patients affected by GAMT deficiency.

Growth Performance and Right Ventricular Hypertrophy Responses of Broiler Chickens to Guanidinoacetic Acid Supplementation under Hypobaric Hypoxia

“…This observation suggests that dietary GAA has oxidant-antioxidant capacity (Ostogic et al, 2015). It has been shown that high levels of GAA could stimulate the generation of reactive oxygen species in the body (Mori et al, 1996), decrease non-enzymatic antioxidant capacity, and increase lipid peroxidation in rats (Zugno et al, 2008). This is observed as a higher heterophils to lymphocytes ratio (H:L) in birds fed GAA at 2 g/kg than in those fed with lower levels of GAA supplementation.…”

Effects of dietary guanidinoacetic acid and betaine supplementation on performance, blood biochemical parameters and antioxidant status of broilers subjected to cold stress

“…GAA induces oxidative stress after experimental intrastriatal infusion (Zugno et al 2008), or excessive accumulation in pathological conditions (Mori et al 1996), while dietary GAA improves antioxidant status by elevating total antioxidant capacity and the activities of several antioxidant enzymes (Wang et al 2012). Contrasting results of the previous studies are accompanied with different levels of GAA achieved after GAA administration/accumulation.…”

Effect of Chronic Treatment with Grape Juice during Pregnancy and Nursing in Central Nervous System of Female Wistar Rats

“…The reduction of oxidative damage by consumption of these products was observed in pregnancy model, where the consumption of seed extract of Euterpe oleracea Mart. (Acai) reduced levels of carbonyl protein in plasma and kidney of female rats fed pregnant fed with a hypoprotein diet [46].…”