Effects of zamzam water on mu-opioid receptor gene expression in morphine dependent subjects
Methadone Maintenance Treatment (MMT) is introduced as a treatment program that involves the long-term prescribing of methadone as an alternative to the opioid. However, the percentage of the client dropped out of the MMT program is increasing proportional to time. Thus, it is important to take all...
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| LEADER | 06108cam a2200361 7i4500 | ||
|---|---|---|---|
| 001 | 0000094750 | ||
| 005 | 20201223090000.0 | ||
| 008 | 181001s2018 my eng | ||
| 040 | |a UniSZA | ||
| 050 | 0 | 0 | |a BP187.48 |
| 060 | 1 | 0 | |a QU 475 |b M697e 2018 |
| 090 | 0 | 0 | |a BP187.48 |b .M64 2018 |
| 100 | 0 | |a Mohamad Halim Mohamad Shariff |e author | |
| 245 | 1 | 0 | |a Effects of zamzam water on mu-opioid receptor gene expression in morphine dependent subjects |c Mohamad Halim bin Mohamad Shariff. |
| 264 | 0 | |c 2018. | |
| 300 | |a xviii, 293 leaves: |b illustrations (some colour); |c 30 cm. | ||
| 336 | |a text |2 rdacontent | ||
| 337 | |a unmediated |2 rdamedia | ||
| 338 | |a volume |2 rdacarrier | ||
| 502 | |a Thesis (Degree of Doctor of Philosophy) - Universiti Sultan Zainal Abidin, 2018 | ||
| 504 | |a Includes bibliographical references (p. 152-189) | ||
| 505 | 0 | |a 1. Introduction -- 2. Literature review -- 3. Methodology -- 4. Results and Discussion -- 5. Conclusion | |
| 520 | |a Methadone Maintenance Treatment (MMT) is introduced as a treatment program that involves the long-term prescribing of methadone as an alternative to the opioid. However, the percentage of the client dropped out of the MMT program is increasing proportional to time. Thus, it is important to take all steps needed to ensure that the client sustain in MMT Program. A series of study reponed that the endocytosis of Mu Opioid Receptor (MOR) reduce the developments of both dependence and withdrawal. Sodium (Na), which is one of the important ion has been reported has the capability to activate MOR and promote endocytosis of the MOR. Hence, zamzam water, which is known as alkaline water that contain higher Na contain as compared to others mineral water might have effects on the regulation of MOR and thus prevent the developments of both dependence and withdrawal. The current study divided into two Phase of study. In Phase I in-vitro study, the level of ion in zamzam water was determined using ion chromatography, then, the safety doses of zamzam water on opioid receptor expressing cell line (U-87 MG glioblastoma cells) was determined by using MTT assay. Then, the cAMP level, which is the marker for dependence in cell, was determined using ELISA kit. The U-87 MG cell line was incubated with morphine (25 !JVmL) for 24 h, purposely to make cell become dependent and then the cell was co-treated with difference concentration of methadone (5, 10, 25 !JM) and 3.2 mL volume of zamzam water. Meanwhile in Phase 2 ill-vivo study, ten animal withdrawal symptoms of morphine-dependent rats, which received different treatments, were observed. Then, the Ventral Tegmental Area (VTA) of rat's brain was dissected and subjected to real-time quantitative RT-PCR to determine the regulation of MOR gene expression. In this experimental study, male Sprague Dawley rats (180-220 g) were randomly divided into 5 groups of 10: namely negative control group, untreated group, methadone treated group, zamzam water treated group, and co-treatment of methadone with zamzam water. Morphine dependency was induced by intraperitoneal injection of increasing doses daily by 2 mglkg increments per day until a maximum of 68 mg/kg for 30 days was achieved. The rats were treated with methadone (2.5 mg/IOO mL), zamzam water (40 mLidaily) and co¬treatment methadone (2.5 mg/IOO mL) with zarnzarn water (40 mLl daily) for 30 days. On days one, seven, fourteen, twenty-one, thirty of treatment, the rats were placed individually into Plexiglas cages and being observed for spontaneous withdrawal symptoms. For gene expression study, rats' brains were removed and the VTA was dissected in separate groups. A quantitative RT-PCR method was used to evaluate the gene expression profile. I n Phase I study, the result indicated that the ion concentration of zamzam water significantly higher than the normal mineral water. Then, next result 3.2 mL of zamzam water or equally to 40 % volume of total medium incubation is a safety doses for this cell line while in cAMP assay, the result show that 3.2 mL of zamzarn water incubated with 10 !J1/mL of methadone prevented the overshoot of cAMP level (p<O.OS) in U-87 MG cell line after 48h incubation. In Phase 2 study, co-treatment methadone (2.5 mgllOO rnl.) and zamzam water (40 mLldaily) was significantly attenuating the spontaneous withdrawal symptoms (body weight loss, diarrhoea, wet dog shake, rare standing and sniffing) of morphine dependent rat compared to others treatment group (p<0.05) after 30 days of treatment. Besides that, zamzam water treated group also shown a decrease in the number of jumping and face grooming. A significant reduction in amount was observed when compared to untreated group in the end of treatment day. Subsequently, in gene expression assay, the data obtained indicated that zamzam water, methadone and co¬treatment of methadone and zamzam water was significantly prevented the down-regulation of MOR expression (p<0.05) in VT A area of morphine dependent rats which is explain the attenuated morphine withdrawal symptoms observed in these group. Besides that, the results also demonstrated that the co-treated rat with both methadone and Zamzam water significantly prevented the down-regulation of MOR expression compared to the rest of the treatment groups showing that Zamzam water has synergistic effects when combine together with methadone. This finding show that Zamzam water have an effects on the regulation of MOR through the down regulation of MOR and decreasing of cAMP level significantly. These effects probably due to the presence of sodium in Zamzam water which bind to MOR and promote the endocytosis of MOR. | ||
| 610 | 2 | 0 | |a Universiti Sultan Zainal Abidin -- |x Dissertations |
| 610 | 2 | 0 | |a Universiti Sultan Zainal Abidin -- |x Faculty of Medicine |
| 650 | 0 | |a Genes | |
| 650 | 0 | |a Zamzam Well (Saudi Arabia) | |
| 650 | 0 | |a Morphine | |
| 650 | 0 | |a Opioid abuse | |
| 650 | 0 | |a Morphine abuse | |
| 655 | 0 | |a Dissertations, Academic | |
| 710 | 2 | |a Universiti Sultan Zainal Abidin | |
| 999 | |a 1000174304 |b Thesis |c Reference |e Medical Thesis Collection | ||