Physical exercise reverses glutamate uptake and oxidative stress effects of chronic homocysteine administration in the rat

Abstract

The influence of physical exercise on the effects elicited by homocysteine on glutamate uptake and some parameters of oxidative stress, namely thiobarbituric acid-reactive substances, 2',7'-dichlorofluorescein (H(2)DCF) oxidation, as well as enzymatic antioxidant activities, superoxide dismutase, catalase and glutathione peroxidase in rat cerebral cortex were investigated. Wistar rats received subcutaneous administration of homocysteine or saline (control) from the 6th to 29th day of life. The physical exercise was performed from the 30th to 60th day of life; 12 h after the last exercise session animals were sacrificed and the cerebral cortex was dissected out. It is shown that homocysteine reduces glutamate uptake increases thiobarbituric acid-reactive substances and disrupts enzymatic antioxidant defenses in cerebral cortex. Physical activity reversed the homocysteine effects on glutamate uptake and on antioxidant enzymes activities; although the increase in thiobarbituric acid-reactive substances was only partially reversed by exercise. These findings allow us to suggest that physical exercise may have a protective role against homocysteine-induced oxidative imbalance and brain damage to the glutamatergic system.

Pistacia Atlantica Extract Enhances Exercise-Mediated Improvement of Antioxidant Defense in Vistar Rats

“…Evidence indicates a change in antioxidative enzymes resulting from exercise training which causes oxidative stress (20).…”

Role of Homocysteine in the Ischemic Stroke and Development of Ischemic Tolerance

“…Hcy mediated NMDA receptor induction of neuronal cells could lead to their death due to the transient activation of extracellular signal-regulated kinases, ERK, MAPK, and p38 MAPK (Poddar and Paul, 2013) that is different from the downstream signaling pathways triggered by other NMDA receptor agonists. The Hcy induced glutamate receptor activated neurotoxicity is widely recognized (da Cunha et al, 2012; Kwon et al, 2014). Interestingly, ischemic insults also activate glutamatergic excitotoxicity with the promotion of neuronal death.…”

“…Plasma Hcy concentration in rats treated via this way achieved the levels similar to those found in homocystinuric patients (moderate hHcy). An increased Hcy level is potent enough to induce and to accumulate hydroxyl radicals as the most powerful free radicals with the ability to remove electrons from other molecules including lipids, proteins, carbohydrates and DNA practically in all cellular components (Kolling et al, 2011; da Cunha et al, 2012; Petras et al, 2014). Thus, as seen from literature data (Streck et al, 2002; Loureiro et al, 2010) and also from our results (Lehotský et al, 2011; Pavlikova et al, 2011; Petras et al, 2014; Kovalska et al, 2015; Lehotsky et al, 2015), chronic elevated levels of Hcy manifest high cellular toxicity.…”

“…The thickened and collapsed processes that poorly extend to the area of pyramidal neurons in the CA1 region and M1 cortex are presumably due to the morphological alterations of astrocytes and cytoskeletal remodeling. This might be an indicator of severity of neuronal injury induced by hHCy (da Cunha et al, 2012; Kwon et al, 2014). Astrocytes are highly plastic cells and their dynamic morphological changes could affect the intercellular communication with surrounding synapses that are important in the development of brain lesions (Buffo et al, 2010).…”

Correlation Between Serum Homocysteine Levels and Outcome of Patients with Severe Traumatic Brain Injury

“…Although this study shows that there is a relationship between the Hcy level changes and prognosis of patients with TBI, no information about the role of Hcy in pathologic trend in terms of cellular and molecular was exist. Moreover, in some studies the mechanisms of neurotoxicity of Hcy for CNS has been shown (25, 26, 13).For example, the neurotoxicity of Hcy is caused by glutaminergic receptors which are the receptors that cause ischemic Islands (7). Some neurons damage mechanisms caused by neurotoxicity of Hcy include: neuron apoptosis induction by caspase pathway (31), change of brain metabolism (33), decreased activity of Na+,K+ ATPase pump(27), increasing intracellular calcium(28), and most important of them is producing of reactive oxygen species (ROC) (21).…”