ascorbic-acid and Lead-Poisoning--Nervous-System

Neurotoxicity induced by exposure to heavy metal lead (Pb) is a concern of utmost importance particularly for countries with industrial-based economies. The developing brain is especially sensitive to exposure to even minute quantities of Pb which can alter neurodevelopmental trajectory with irreversible effects on motor, emotive-social and cognitive attributes even into later adulthood. Chemical synapses form the major pathway of inter-neuronal communications and are prime candidates for higher order brain (motor, memory and behavior) functions and determine the resistance/susceptibility for neurological disorders, including neuropsychopathologies. The synaptic pathways and mechanisms underlying Pb-mediated alterations in neuronal signaling and plasticity are not completely understood. Employing a biochemically isolated synaptosomal fraction which is enriched in synaptic terminals and synaptic mitochondria, this study aimed to analyze the alterations in bioenergetic and redox/antioxidant status of cerebellar synapses induced by developmental exposure to Pb (0.2 %). Moreover, we test the efficacy of vitamin C (ascorbate; 500 mg/kg body weight), a neuroprotective and neuromodulatory antioxidant, in mitigation of Pb-induced neuronal deficits. Our results implicate redox and bioenergetic disruptions as an underlying feature of the synaptic dysfunction observed in developmental Pb neurotoxicity, potentially contributing to consequent deficits in motor, behavioral and psychological attributes of the organisms. In addition, we establish ascorbate as a key ingredient for therapeutic approach against Pb induced neurotoxicity, particularly for early-life exposures.

Topics: Animals; Antioxidants; Ascorbic Acid; Cerebellum; Energy Metabolism; Female; Glutathione; Lead; Lead Poisoning, Nervous System; Male; Neuroprotective Agents; Organ Size; Oxidative Stress; Pregnancy; Rats; Rats, Wistar; Synapses; Synaptosomes

In the present study, we investigated the effects of ascorbic acid on lead-exposed developing cerebellum. Female rats were divided into the following three groups: control (distilled water), lead (0.2% lead acetate), and lead plus ascorbic acid (100 mg/kg/day, 10% solution). To evaluate the effect of lead exposure and ascorbic acid treatment accurately on the cerebellar development for the gestational period, we halted further treatment with lead and ascorbic acid in the dams after delivery of the pups. Although the ascorbic acid slightly decreased the lead level in pups, lead level was still high in the group treated with lead plus ascorbic acid group compared with the control group. The blood lead levels indicated that the ascorbic acid could facilitate both the excretion and transfer of lead from a dam to its pups via milk. At postnatal day 21, lead exposure significantly reduced the number of Purkinje cells in the cerebellar cortex of pups. Additionally, lead treatment induced degenerative changes such as reduction of glutamic acid decarboxylase (GAD67) and c-kit expressions are observed in the developing cerebellar cortex. In the cerebellum of the pups from the lead plus ascorbic acid group, reduction of the number of Purkinje cells, GAD67 expression, and c-kit immunopositivity were remarkably restored compared with the lead group. Our present results suggested that ascorbic acid treatment to lead-exposed dam exerted protective effects on the developing cerebellum against lead-induced neurotoxicity.

Topics: Animals; Animals, Newborn; Antioxidants; Ascorbic Acid; Cerebellar Cortex; Female; Glutamate Decarboxylase; Immunohistochemistry; Lead; Lead Poisoning, Nervous System; Pregnancy; Prenatal Exposure Delayed Effects; Proto-Oncogene Proteins c-kit; Purkinje Cells; Rats

We carried out animal experiments based on the orthogonal design L(8)(2(7)) setting seven factors with two different levels of each and 10 groups of rats. The nutrients tested were tyrosine, glycine, methionine, taurine, ascorbic acid, thiamine and zinc.. The objective of this study was to explore the optimal combinations of nutrients for prevention or amelioration of lead-induced learning and memory impairment.. Rats were supplemented with nutrients by gavage once a day in two experiments: one was simultaneous nutrient supplementation with lead acetate administration (800 mg l(-1)) for 8 weeks (prophylactic supplementation) and the other was nutrient supplementation for 4 weeks after the cessation of 4 weeks of lead administration (remedial supplementation). Morris water maze was initiated at ninth week. Rats were terminated for assays of levels of Pb in blood, activities of superoxide dismutase (SOD) and nitric oxide synthase (NOS) in hippocampus, levels of nitric oxide (NO) in hippocampus and expressions of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclic adenosine monophosphate (cAMP) response element-binding protein messenger RNA in hippocampus.. Results showed that in prophylactic supplementation, methionine, taurine, zinc, ascorbic acid and glycine were the effective preventive factors for decreasing prolonged escape latency, increasing SOD and NOS activities and NO levels in the hippocampus, respectively. On the other hand, in remedial supplementation, taurine was the effective factor for reversing Pb-induced decrease in activities of SOD, NOS and levels of NO.. In conclusion, the optimum combinations of nutrients appear to be methionine, taurine, zinc, ascorbic acid and glycine for the prevention of learning and memory impairment, while taurine and thiamine appear to be the effective factors for reversing Pb neurotoxicity.

Topics: Animals; Antioxidants; Ascorbic Acid; Food; Glycine; Hippocampus; Lead Poisoning; Lead Poisoning, Nervous System; Learning Disabilities; Male; Maze Learning; Memory Disorders; Methionine; Models, Animal; Organometallic Compounds; Rats; Rats, Sprague-Dawley; Taurine; Thiamine; Tyrosine; Zinc

The aim of this study was to determine whether changes in the activities of antioxidant enzymes occur in the brain of lead-exposed rats (300mgPb/L in drinking water) and to investigate the potential benefit of the administration of some natural antioxidants (Zn 20mg/L+vitamins A 50.000U/L, C 2g/L, E 500mg/L and B6 500mg/L) during pregnancy and lactation. Lead exposure caused a significant increase in brain TBARS (23%) vs. control, whereas co-administration of antioxidants+lead was effective in reducing TBARS levels. The catalase activity in brain samples of the lead group was enhanced 99% vs. control, but no changes were found in the remainder of the groups. No statistically significant effect of lead and/or antioxidants in brain SOD activity was noted. Acid phosphatase activity was enhanced in both lead groups but no changes were found in alkaline phosphatase activity. Finally, a statistically significant decrease (-35%) of acetylcholinesterase activity was noted in the lead+antioxidants group. This study provides evidence of the beneficial role of antioxidants in early status of brain development in rats against lead exposure.

Topics: Acetylcholinesterase; Animals; Antioxidants; Ascorbic Acid; Body Weight; Brain; Catalase; Female; Lead Poisoning, Nervous System; Lipid Peroxides; Organ Size; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin A; Vitamin B 6; Vitamin E; Zinc