Neuroprotective Effect of Diosmin on Arsenic Trioxide Induced Neurotoxicity in Albino Wistar Rats.

Gangireddy, K (2014) Neuroprotective Effect of Diosmin on Arsenic Trioxide Induced Neurotoxicity in Albino Wistar Rats. Masters thesis, Swamy Vivekanandha College of Pharmacy, Tiruchengode.

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Abstract

The present study the term ‘neurotoxic’ is used to describe a substance, condition or state that damages the nervous system and/or brain, usually by killing neurons. Arsenic is a semi-metalloid and exposure to As is a worldwide health problem causing various disorders and diseases in millions of people around the world. Arsenic causes various diseases such as numerous organ cancers and also patients show severe effects on their nervous system. However, the mechanisms of As neurotoxicity remain somewhat obscure while the instance of As exposure remains a prevalent human health concern.114 Diosmin is a semisynthetic flavone derivative of hesperidin occur naturally in citrus fruits. The drug is widely used in treatment of varicose veins and venous ulcers, lymphatic insuffi ciency and hemorrhoids. In these conditions, Diosmin exerts a venotonic action, decreasing venous reflux, and thereby alleviating edema and providing effective venous drainage.115 Moreover, the drug has been shown to provide better outcomes for patients with impaired cardiac function before undergoing cardiac operations that require cardiopulmonary bypass. These effects of Diosmin can be ascribed to the antiinflammatory, microcirculatory, and antioxidant effects of its flavonoid substances. In this context, Diosmin has been shown to decrease the levels of granulocyte and macrophage infi ltration into the infl amed tissues as well as leucocyte adhesion to the vascular endothelium. The decrease in release of oxygen free radicals, cytokines, and proteolytic matrix metalloproteinases from activated infl ammatory and endothelial cells, results in lower levels of inflammation, decreased microvascular permeability and decreased leukocyte-dependent endothelial damage. Diosmin decreases vascular permeability more than any of its single constituents, suggesting that the flavonoids present in its formulation have a synergistic action. The drug possesses an antioxidant effect, significantly decreasing the level of hydroxyl free radicals, increasing free SH-group concentration, and natural scavenger capacity.115 The effects of arsenic on nervous system have received considerably less attention. In this study we planned to investigate the effects of Arsenic trioxide on the oxidative stress, contents of lipids, proteins, antioxidant defence systems in various regions of the rat brain to seek contribution of arsenic, if any, in peroxidative damage and other neurochemical perturbations. Furthermore, to unravel the effects of recovery on arsenic induced neurotoxicity in various regions of the rat brain. The present study attempts to screen the arsenic poisoning particularly the role of oxidative stress in the toxic manifestation, an attempt for the treatment and a possible beneficial role of antioxidants supplementation to achieve the optimum effects in wistar rats. CONCLUSION: In summary, the results of the present study suggest that arsenic neurotoxicity in rats initiated peroxidative reactions in membrane lipids of the brain. The present study demonstrates the inhibitory effect of Diosmin pretreatment on the brain oxidative stress in an in vivo model. Histopathological evaluation revealed the neuroprotective effect of Diosmin mainly at a dose of Diosmin 100 mg/kg. Treatment with Diosmin revealed a significant amelioration in arsenic induced neurotoxicity showing its protective effect by improving the Biogenic amines in various regions of brain and the AchE levels in serum and brain. These findings derive the significance of Diosmin in ameliorating the oxidative stress and neuroinflammation which are important contributors in the pathogenesis of several neurodegenerative disorders. Furthermore, it is implicated that arsenic is a de-myelinating agent. And may alter neuronal functions followed by CNS dysfunctions. Much remains to be learned about this ancient neurotoxicant. It is planned in future to study the effects of arsenic in brain with respect to myelin structure and functions, DNA and RNA levels and to seek a correlation with oxidant stress, and to estimate the levels of antioxidant defence system enzymes.

Item Type: Thesis (Masters)
Uncontrolled Keywords: Neuroprotective Effect; Diosmin; Arsenic Trioxide Induced Neurotoxicity; Albino Wistar Rats
Subjects: PHARMACY > Pharmacology
Depositing User: Ravindran C
Date Deposited: 20 Oct 2017 07:21
Last Modified: 20 Oct 2017 07:21
URI: http://repository-tnmgrmu.ac.in/id/eprint/3731

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