Metabolomics study of carbamazepine induced oxidative stress and potential role of tocotrienol rich fraction / Mohd Ikhwan Ismail

Metabolomics study of carbamazepine induced oxidative stress and potential role of tocotrienol rich fraction / Mohd Ikhwan Ismail

Carbamazepine is mainly used in the treatment of epilepsy, bipolar disorder and trigerminal neuralgia. However, it causes severe adverse drug reactions which include Steven Johnson Syndrome and/or Toxic Epidermal Necrolysis. Mechanisms leading to the adverse effects are hypothesised to involve produ...

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Main Author: Ismail, Mohd Ikhwan
Format: Thesis
Language:English
Published: 2014
Online Access:https://ir.uitm.edu.my/id/eprint/18394/2/TM_MOHD%20IKHWAN%20ISMAIL%20PH%2014_5.pdf
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spelling my-uitm-ir.183942022-03-01T02:56:58Z Metabolomics study of carbamazepine induced oxidative stress and potential role of tocotrienol rich fraction / Mohd Ikhwan Ismail 2014 Ismail, Mohd Ikhwan Carbamazepine is mainly used in the treatment of epilepsy, bipolar disorder and trigerminal neuralgia. However, it causes severe adverse drug reactions which include Steven Johnson Syndrome and/or Toxic Epidermal Necrolysis. Mechanisms leading to the adverse effects are hypothesised to involve production of reactive metabolites which deplete the antioxidant enzymes and therefore subjecting the individuals to oxidative stress. Hence, this study aims to determine the changes in the metabolism pathways involved in CBZ therapy which changes in the metabolite profiles of rats treated with different doses of CBZ were investigated and administration of tocotrienol rich fraction (TRF) were also studied to understand the potential roles of TRF in reducing the side effects of CBZ. Thirty-six (36) SD rats were used in this study. Three (3) different doses of CBZ, one (1) dose of CBZ+TRF and one (1) control (1 mL of normal saline) were given orally to 5 groups of SD rats. All sera and organs were collected after day 7,h of treatments. All samples were subjected to biochemical assays (liver function test, lipid peroxidation and antioxidant) and metabolomic analysis using LCMS-QTOF platform. Based on the metabolite profiling and metabolic pathway analysis, CBZ treated rats showed pertubation in the metabolism of four (4) metabolic pathways which include tryptophan, glutathione, purine and arginine-proline metabolism. These four (4) metabolic pathways in the treatment of CBZ which is related to the oxidative phosphorylation or oxidant-antioxidant balance system. On the other hand, TRF was found to have effects on the CBZ treated rats by restoring the antioxidant capacities via the four (4) major metabolic pathways mentioned above. 2014 Thesis https://ir.uitm.edu.my/id/eprint/18394/ https://ir.uitm.edu.my/id/eprint/18394/2/TM_MOHD%20IKHWAN%20ISMAIL%20PH%2014_5.pdf text en public mphil masters Universiti Teknologi MARA Faculty of Pharmacy
institution Universiti Teknologi MARA
collection UiTM Institutional Repository
language English
description Carbamazepine is mainly used in the treatment of epilepsy, bipolar disorder and trigerminal neuralgia. However, it causes severe adverse drug reactions which include Steven Johnson Syndrome and/or Toxic Epidermal Necrolysis. Mechanisms leading to the adverse effects are hypothesised to involve production of reactive metabolites which deplete the antioxidant enzymes and therefore subjecting the individuals to oxidative stress. Hence, this study aims to determine the changes in the metabolism pathways involved in CBZ therapy which changes in the metabolite profiles of rats treated with different doses of CBZ were investigated and administration of tocotrienol rich fraction (TRF) were also studied to understand the potential roles of TRF in reducing the side effects of CBZ. Thirty-six (36) SD rats were used in this study. Three (3) different doses of CBZ, one (1) dose of CBZ+TRF and one (1) control (1 mL of normal saline) were given orally to 5 groups of SD rats. All sera and organs were collected after day 7,h of treatments. All samples were subjected to biochemical assays (liver function test, lipid peroxidation and antioxidant) and metabolomic analysis using LCMS-QTOF platform. Based on the metabolite profiling and metabolic pathway analysis, CBZ treated rats showed pertubation in the metabolism of four (4) metabolic pathways which include tryptophan, glutathione, purine and arginine-proline metabolism. These four (4) metabolic pathways in the treatment of CBZ which is related to the oxidative phosphorylation or oxidant-antioxidant balance system. On the other hand, TRF was found to have effects on the CBZ treated rats by restoring the antioxidant capacities via the four (4) major metabolic pathways mentioned above.
format Thesis
qualification_name Master of Philosophy (M.Phil.)
qualification_level Master's degree
author Ismail, Mohd Ikhwan
spellingShingle Ismail, Mohd Ikhwan
Metabolomics study of carbamazepine induced oxidative stress and potential role of tocotrienol rich fraction / Mohd Ikhwan Ismail
author_facet Ismail, Mohd Ikhwan
author_sort Ismail, Mohd Ikhwan
title Metabolomics study of carbamazepine induced oxidative stress and potential role of tocotrienol rich fraction / Mohd Ikhwan Ismail
title_short Metabolomics study of carbamazepine induced oxidative stress and potential role of tocotrienol rich fraction / Mohd Ikhwan Ismail
title_full Metabolomics study of carbamazepine induced oxidative stress and potential role of tocotrienol rich fraction / Mohd Ikhwan Ismail
title_fullStr Metabolomics study of carbamazepine induced oxidative stress and potential role of tocotrienol rich fraction / Mohd Ikhwan Ismail
title_full_unstemmed Metabolomics study of carbamazepine induced oxidative stress and potential role of tocotrienol rich fraction / Mohd Ikhwan Ismail
title_sort metabolomics study of carbamazepine induced oxidative stress and potential role of tocotrienol rich fraction / mohd ikhwan ismail
granting_institution Universiti Teknologi MARA
granting_department Faculty of Pharmacy
publishDate 2014
url https://ir.uitm.edu.my/id/eprint/18394/2/TM_MOHD%20IKHWAN%20ISMAIL%20PH%2014_5.pdf
_version_ 1783733672044658688

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