Influence of Alpha Lipoic Acid on D-Galactosamine Induced Oxidative mediated DNA damage

26063746, - (2008) Influence of Alpha Lipoic Acid on D-Galactosamine Induced Oxidative mediated DNA damage. Masters thesis, Vel’s College of Pharmacy, Chennai.

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Abstract

Alpha lipoic acid is “Multi functional Antioxidant”. It protects cell membrane from free radical attack, augments the body’s entire antioxidant network including glutathione & coenzyme Q10, directly and indirectly reduces DNA damage, it improves mitochondrial antioxidant on oxidative condition, and ALA is an important antioxidant that helps to recycle other non-enzymic antioxidants (Vitamin C, E, and Reduced glutathione) to fight against fat-soluble and water-soluble free radical attacks. D-galactosamine induction had been drastically increase the serum marker enzymes levels (AST, ALT, ALP, LDH) this has been clearly shows the membrane damage in hepatocytes but in this study pre-treatment with alpha lipoic acid significantly reduce the marker enzymes levels in serum thus the hepatoprotectivity activity might be due to the membrane stabilising action of ALA. Liver is exposed to potent drugs and toxic chemical (D-galactosamine) which has been produces the free radicals very rapidly that free radical assault the lipids present in the hepatocytes and this condition instantly leads to lipid peroxidation which exhibit the byproduct called MDA. So lipid peroxidation effect is measuring by MDA levels. In our study GalN administration generating the free radicals and increase the lipid peroxidation levels but pre treatment with alpha lipoic acid significantly reduces the lipid peroxidation by scavenging the superoxide, hydroxyl, peroxyl radicals; single oxygen radicals by this mechanism ALA weaken the d-galactosamine induced lipid peroxidation. In this study GalN induced lipid peroxidation significantly decline the GSH levels because rapid production of lipid peroxidation are effectivelely counteracted by GSH but the fast generation of radicals completely reduces the GSH concentration in tissue and also reduces the enzymic antioxidant levels but pre treatment with alpha lipoic acid increase the GSH level in tissue this can be occur by increasing the cysteine availability enhancer like ALA because cysteine is rate limiting enzyme in inter cellular GSH bio synthesis. ROS are scavenged by antioxidant enzymes like SOD, CAT, GPX, and GR.ALA ultimately influence on SOD apart from increasing the GSH levels. SOD primary antioxidant enzymes which has been directly converts the singlet oxygen radicals to hydrogen peroxide in the second step CAT and GPx involved to convert the hydrogen peroxide in to water and oxygen. GR not having any specific action but its help to convert the oxidised glutathione in to reduce one. In this study GalN injection markedly reduces the enzymic antioxidant levels but pre treatment with alpha lipoic acid improving the antioxidant enzymes which clearly exemplifies the antioxidant potency of ALA. Histopathological observation reveals thus the GalN induction group shows centre lobular necrosis with severe inflammation in tissue which has been effectively reduce in ALA treatment group. In this study GalN administration cause DNA fragmentation which indicates the cell death process this is due to the generation of free radicals. Pre-treatment with alpha lipoic acid effectively reduces the DNA damage by scavenging the ROS generated by GalN. In Conclusion, the results of this study demonstrate that the administration of GalN induced extensive oxidative stress in liver, which is associated with membrane damage and hepatocytes dysfunction. ALA supplementation may reduce oxidative stress in liver of GalN treated rats by decreasing the lipid peroxidation and ROS propagation by scavenging free radicals, or by improving the actions of antioxidant enzymes. The function of ALA in the regulation of GSH and intercellular antioxidant may be significant in the restitution of redox status and it reduces the DNA damage induced by GalN administration.

Item Type: Thesis (Masters)
Additional Information: (Reg. No. 26063746)
Uncontrolled Keywords: Alpha Lipoic Acid ; D-Galactosamine ; Induced Oxidative ; mediated ; DNA damage.
Subjects: PHARMACY > Pharmaceutical Biotechnology
Depositing User: Subramani R
Date Deposited: 03 Oct 2018 15:37
Last Modified: 03 Oct 2018 15:37
URI: http://repository-tnmgrmu.ac.in/id/eprint/9653

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