Hereditary fructose intolerance is an autosomal recessive disorder characterized by the accumulation of fructose in tissues and biological fluids of patients. The disease results from a deficiency of aldolase B, responsible for metabolizing fructose in the liver, kidney, and small intestine. We investigated the effect of acute fructose administration on oxidative stress and neuroinflammatory parameters in the cerebral cortex of 30-day-old Wistar rats. Animals received subcutaneous injection of sodium chloride (0.9 %) (control group) or fructose solution (5 μmol/g) (fructose group). One hour later, the animals were euthanized and the cerebral cortex was isolated. Oxidative stress (levels of thiobarbituric acid-reactive substances (TBA-RS), carbonyl content, nitrate and nitrite levels, 2',7'-dihydrodichlorofluorescein (DCFH) oxidation, glutathione (GSH) levels, as well as the activities of catalase (CAT) and superoxide dismutase (SOD)) and neuroinflammatory parameters (TNF-α, IL-1β, and IL-6 levels and myeloperoxidase (MPO) activity) were investigated. Acute fructose administration increased levels of TBA-RS and carbonyl content, indicating lipid peroxidation and protein damage. Furthermore, SOD activity increased, whereas CAT activity was decreased. The levels of GSH, nitrate, and nitrite and DCFH oxidation were not altered by acute fructose administration. Finally, cytokines IL-1β, IL-6, and TNF-α levels, as well as MPO activity, were not altered. Our present data indicate that fructose provokes oxidative stress in the cerebral cortex, which induces oxidation of lipids and proteins and changes of CAT and SOD activities. It seems therefore reasonable to propose that antioxidants may serve as an adjuvant therapy to diets or to other pharmacological agents used for these patients, to avoid oxidative damage to the brain.

Maple Syrup Urine Disease (MSUD) is biochemically characterized by elevated levels of leucine, isoleucine and valine, as well as their corresponding transaminated branched-chain α-keto acids in tissue and biological fluids. Neurological symptoms and cerebral abnormalities, whose mechanisms are still unknown, are typical of this metabolic disorder. In the present study, we evaluated the early effects (1 h after injection) and long-term effects (15 days after injection) of a single intracerebroventricular administration of α-ketoisocaproic acid (KIC) on oxidative stress parameters and cognitive and noncognitive behaviors. Our results showed that KIC induced early and long-term effects; we found an increase in TBARS levels, protein carbonyl content and DNA damage in the hippocampus, striatum and cerebral cortex both one hour and 15 days after KIC administration. Moreover, SOD activity increased in the hippocampus and striatum one hour after injection, whereas after 15 days, SOD activity decreased only in the striatum. On the other hand, KIC significantly decreased CAT activity in the striatum one hour after injection, but 15 days after KIC administration, we found a decrease in CAT activity in the hippocampus and striatum. Finally, we showed that long-term cognitive deficits follow the oxidative damage; KIC induced impaired habituation memory and long-term memory impairment. From the biochemical and behavioral findings, it we presume that KIC provokes oxidative damage, and the persistence of brain oxidative stress is associated with long-term memory impairment and prepulse inhibition.