Acute and long-term effects of intracerebroventricular administration of α-ketoisocaproic acid on oxidative stress parameters and cognitive and noncognitive behaviors.

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.

Genotoxic And Cytotoxic Effects Of Oral Vanadyl Sulphate.

BACKGROUND: Vanadyl sulphate is available as herbal medicine against diabetes mellitus and body building supplement, over the counter worldwide. The available data on its safety is controversial and inadequate. The objective of this study was to analyse its safety in usual therapeutic dose range. METHODS: It was an experimental study carried out at the Department of Biochemistry & Molecular Biology, Army Medical College, National University of Medical Sciences (NUMS), Rawalpindi, Pakistan, from Jun 2014 to Oct 2018. The study was carried out on 105 Sprague Dawley rats for duration of 24 weeks. The animals were randomly distributed in three groups of 35 each. The group I rats were marked as control while rats of group II & III were administered vanadyl sulphate 0.06mg/day and 0.3mg/day respectively. Alanine amino transferase (ALT) and Malondialdehyde (MDA) were measured in serum while comet assay was performed on WBCs. RESULTS: The plasma levels of ALT and MDA were significantly raised in group II and III subjects. Single cell gel electrophoresis (SCGE) / comet assay showed minimal "tail moment" in control group and increased tail moment in group II and III in a dose dependent manner which indicates dsDNA breaks. CONCLUSIONS: It was observed that vanadyl sulphate causes hepatocellular toxicity, oxidative stress and damage to the DNA in usual therapeutic/ supplemental doses. Due to hazardous effects, its use in humans as alternate medicine may be reviewed.

The impact of occupational exposure to traffic-related air pollution among professional motorcyclists from Porto Alegre, Brazil, and its association with genetic and oxidative damage.

Vehicles play an important role in modern life; however, they also generate hazards. Occupational exposed subjects are in long-term contact with harmful products, which sets these professionals in a susceptible group to air pollutant damage. The aims of this study were to quantify individual exposure to pollutant gases and chemical elements and to evaluate oxidative and genetic damage in professional motorcyclists and office workers. We recruited professional motorcyclists and office workers from Porto Alegre, Brazil, between January and December 2016. Individual exposure to air pollutants was assessed by passive monitoring. Fingernail trace elements were determined by using inductively coupled plasma mass spectrometry. Oxidative stress biomarkers were quantified spectrophotometrically, and genotoxicity was evaluated by micronuclei assay. Individual exposure to NO2 and O3, trace element content (Sb, Pt, As, Cd, V, Mn, and Co), oxidative stress factors, and genetic damage were statistically higher in professional motorcyclists (p < 0.05). Moreover, NO2 and O3 levels showed very strong positive correlation with plasmatic lipid peroxidation (p < 0.001 and r = 0.8849 and 0.8995) and strong positive correlation with micronuclei frequency (p < 0.001 and r = 0.7683 and 0.7280). Results suggest that professional motorcyclists are at high risk due to long-term air pollution exposure, which implies in the onset of several harmful effects and worsening of pre-existent diseases.