Dose‐dependent protective effect of selenium in rat model of Parkinson's disease: neurobehavioral and neurochemical evidences

Abstract

Normal cellular metabolism produces oxidants that are neutralized within cells by antioxidant enzymes and other antioxidants. An imbalance between oxidant and antioxidant has been postulated to lead the degeneration of dopaminergic neurons in Parkinson's disease. In this study, we examined whether selenium, an antioxidant, can prevent or slowdown neuronal injury in a 6-hydroxydopamine (6-OHDA) model of Parkinsonism. Rats were pre-treated with sodium selenite (0.1, 0.2 and 0.3 mg/kg body weight) for 7 days. On day 8, 2 lL 6-OHDA (12.5 lg in 0.2% ascorbic acid in normal saline) was infused in the right striatum. Two weeks after 6-OHDA infusion, rats were tested for neurobehavioral activity, and were killed after 3 weeks of 6-OHDA infusion for the estimation of glutathione peroxidase, glutathione-S-transferase, glutathione reductase, glutathione content, lipid peroxidation, and dopamine and its metabolites. Selenium was found to be successful in upregulating the antioxidant status and lowering the dopamine loss, and functional recovery returned close to the baseline dose-dependently. This study revealed that selenium, which is an essential part of our diet, may be helpful in slowing down the progression of neurodegeneration in parkinsonism.

Selenoprotein H Is a Redox-sensing High Mobility Group Family DNA-binding Protein That Up-regulates Genes Involved in Glutathione Synthesis and Phase II Detoxification

“…Selenium supplementation was found to sustain the GSH levels in the striatum in mice treated with 6-hydroxydopamine (21). Our unpublished data show that the mRNA levels of mSelH in HT22 cells are highly up-regulated by selenium supplementation; therefore, a possible contribution of the gene regulatory function of SelH should be considered in interpreting potential beneficial effects of selenium supplementation in chronic diseases of oxidative stress.…”

Impact of Selenium on Mood and Quality of Life: A Randomized, Controlled Trial

“…There are a number of indications that selenium is important to the brain: during selenium depletion the brain receives a priority supply (Behne et al 1988;Buckman et al 1993;Whanger 2001); neurotransmitter turnover rate is altered in selenium deficiency (Castano et al 1997); selenium supplementation can reduce intractable epileptic seizures (Weber et al 1991, Ramaekers 1994; low plasma selenium levels in the elderly have been associated with senility and accelerated cognitive decline (Berr et al 2000); Alzheimer's patients have lower brain selenium concentrations than controls (Corrigan et al 1991); sodium selenite protected against dopamine loss in a rat model of Parkinson's disease (Zafar et al 2003); a selenoenzyme (GPx1) protected against neuron loss in a mouse stroke model (Crack et al 2001). Furthermore, as the brain is deficient in catalase (Halliwell and Gutteridge 1985), peroxidation products such as H 2 O 2 and lipid peroxides must be removed by the antioxidant selenoenzymes.…”

Selenium in the therapy of neurological diseases. Where is it going?

“…Summary of selenium therapy effects in neurological diseases. Aß-amyloid β, CAT-catalase,GPx-glutathione peroxidase, GSHglutathione, pTau-phosphorylated tau protein, Sel-selenoprotein, SOD-superoxide dismutase [167,[217][218][219].…”