Abstract

This study was designed to investigate neuro-behavioral, neuro-biochemical and neuro-morphological alterations induced by sub-acute toxicity of lead (Pb) in male Wistar rats as well as the assessment of the neuroprotective effect of thiamine hydrochloride against Pb-induced behavioral, biochemical and morphological neuro-alterations. For this purpose 24 male Wistar rats were randomly divided into 4 groups (n=6). Rats in the 1st group were treated with lead acetate orally at dose of 100 mg/kg b.wt. Animals in 2nd group were received leaded water orally + 100 mg/kg thiamine hydrochloride intraperitoneally. 3rd group were treated only with thiamine hydrochloride. 4th group was served as the control animals. Animals were exposed to treatments once daily for 7 consecutive days. Behavioral alterations were assessed by applying neurological tests as elevated plus-maze and Morris water maze. The main neurotransmission systems as cholinergic, adrenergic, serotonergic and GAB Aergic were evaluated in brain tissue homogenate. Morphological alterations was assessed histopathologically. Results revealed that, Pb exposure caused spatial learning and memory impairment, as well as a significant increase in the content of acetylcholine, serotonin and norepinephrine while the activity of acetylcholinesterase and GABA content showed a significant decrease. Hemorrhage in brain, mild perivascular edema and perivascular cuffing were the main pb-induced morphological alterations. Simultaneous administration of thiamine markedly ameliorated Pb-induced neurotoxicity which was indicated by comparatively better behavioral performance, alleviation of the neurotransmitters disturbances and decreased the severity of histopathological lesions. In conclusion, thiamine has been found to be extremely significant in the fighting of Pb-induced neuro-manifestations.

Highlights

  • Lead (Pb) is a wide spread toxic metal found in the environment and considered a potential danger for human and animal health

  • Neurobehavioral alterations Morris water maze (MWM) test: Rats in control group, thiamine treated group and Pb+thiamine treated group solve water maze in a little time 6.75±3.20, 5.50±1.85 and 8.75±1.25 sec, respectively, while the longer time taken by Pb only exposed group (25.00±2.86 Sec) (Figure 1)

  • Rats treated by Pb + thiamine spent a relatively longer period in open arm and a shorter period in closed arm when compared with Pb only exposed animals

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Summary

Introduction

Lead (Pb) is a wide spread toxic metal found in the environment and considered a potential danger for human and animal health. It is known that Pb has detrimental effects on the central and peripheral nervous systems causing behavioral abnormalities, learning impairment, decreased hearing, and impaired cognitive functions in humans and laboratory animals (Bijoor et al, 2012). Pb encephalopathy include: damage of the endothelial cell of the blood-brain barrier leading to entry of Pb into the brain, followed by morphologic and biochemical effects such as impairment of timed programming of cell-cell connections, interferes with neurotransmitter function and disrupts calcium metabolism which is a critical component of numerous biochemical and metabolic functions in the brain (Goyer and Clarkson, 2001). N-methyl-Daspartate (NMDA) receptor (excitatory amino acid receptor play an important role in learning and memorizing) in the hippocampus region is an important target of Pb during the developmental period (Zhu et al, 2005)

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