Structural and Behavioural Changes in Rat Hippocampus Induced by Methotrexate and The potential ameliorative effect of Alpha lipoic acid.

Abstract

Background: Methotrexate (MTX) is a chemotherapy drug associated with cognitive insufficiency in cancer patients treated with chemotherapy.. Alpha lipoic acid (ALA) has been referred to as the "universal antioxidant" because of its unique antioxidant properties. Aim: To inspect the effect of MTX on the hippocampus and to correlate them with the cognition impairment and to assess the practical neuroprotective role of ALA on hippocampus. Material and Method: Thirty two male adult albino were classified into four groups: control group (Physiologic saline), ALA group: (200 mg/kg orally for three weeks), MTX group: (250 mg/ kg) as a single dose intraperitoneally injected and MTX +ALA group: rats were administrated a single dose of intraperitoneal injection of MTX (250 mg/ kg) in the fourth day and were given ALA in a dose of 200 mg/kg orally for three weeks starting from the first day. All animals were subjected to Morris Water Maze testing to assess the hippocampus functions. At the end of the experiment, all animals anesthetized, cerebrum removed and the specimen subjected to histological procedures and biochemical examination. Results: MTX caused impaired performance of Morris Water Maze of rats and biochemical changes significant decrease in oxidative enzymes and increase in malondialdehyde (MDA) tissue levels. Moreover, MTX caused histological changes in rat hippocampus in the form of degenerative and apoptotic neurons which confirmed by immnnohistochemical staining of caspase-3 and GFAP staining and morphometrical analysis of pyramidal cell layer thickness and pyramidal cell count. Co-administration of ALA with MTX significantly diminished the behavioral affection and biochemical changes in rat treated with MTX and ameliorated the histological changes of hippocampus tissue. Conclusion: Our experimental results proved the harmful effect of MTX on hippocampus tissue that explained the cognitive impairment that associated with MTX and confirm the antioxidant and the antiapoptotic properties of ALA on hippocampus tissue.

The Impact of Alpha-lipoic acid on the Monosodium Glutamate Induced Motor Coordination Dysfunction in Rats

“…3-ALA pretreated MSG-administered group (ALA pretreated) (n=10 rats): 200 mg/kg BW of ALA provided from (Chemical industries development, Giza, Egypt) was dissolved in 2 ml of (5% ethanol mixed with olive oil, ethanol/corn oil, 1:19 v/v) (7) , given orally, for three weeks. Then MSG (as in MSG group) given orally, and 2 ml of (5% ethanol mixed with olive oil, ethanol/olive oil, 1:19 v/v) given orally once daily, for another three weeks.…”

“…Due to these advantages, ALA has been proposed as a potential therapeutic agent for a number of chronic diseases with significant economic, social, and epidemiological consequences, including diabetes mellitus and its complications, hypertension, Alzheimer's disease, Down syndrome, cognitive impairment, and some types of cancer. In the medical and nutritional care of patients, ALA is suggested as a dietary supplement (7) .…”

“…It was discovered that ALA dramatically improved muscular coordination and strength, and that its capacity to lower induced lipid peroxidation by scavenging ROS was responsible for its protective impact against tardive dyskinesia (7) .…”

A comparative study of scopolamine, D-Galactose and AlCl3-induced Alzheimer’s like disease by enhancing hippocampal neurodegeneration and memory impairment in male rats

“…AD patients suffer from memory loss and other cognitive deficits due to cholinergic neurons degenerating or loss of neurons in the hippocampus and cortex (Kumar et al, 2018). The hippocampus is a section of the limbic system (Alsemeh et al, 2020). It has a very distinctive shape, composed of two areas: the dentate gyrus (DG) and the Cornu Ammonis (CA), which mainly contain the pyramidal cells and the granule cells, respectively.…”