Recirculating bioavailable nicotine metabolite using ascorbic acid: A pragmatic approach for treating nicotine dependence
Nicotine undergoes metabolism, converting into the oxidized metabolite cotinine, which can persist in the body for several weeks and potentially lead to fatal conditions, such as cancer. Conventional nicotine replacement therapy provides additional nicotine to the body, thereby increasing the chance...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Advances in Redox Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667137923000292 |
| _version_ | 1827316936142225408 |
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| author | Murugesan Arumugam Raman Lakshmi Sundaram Vishal Jayajothi Manish Arul Jerad A Suresh Sathesh Kumar Kesavan |
| author_facet | Murugesan Arumugam Raman Lakshmi Sundaram Vishal Jayajothi Manish Arul Jerad A Suresh Sathesh Kumar Kesavan |
| author_sort | Murugesan Arumugam |
| collection | DOAJ |
| description | Nicotine undergoes metabolism, converting into the oxidized metabolite cotinine, which can persist in the body for several weeks and potentially lead to fatal conditions, such as cancer. Conventional nicotine replacement therapy provides additional nicotine to the body, thereby increasing the chance of accumulating the toxic metabolite cotinine. Consequently, we proposed a hypothesis: converting cotinine back into nicotine using a suitable reducing agent, such as ascorbic acid, could be a practical approach. This conversion would allow cotinine to be reutilized for its central nervous system effects before its eventual elimination from the body. In the current study, we examined this hypothesis by using plasma samples from smokers. Volunteers (both non-smokers and smokers) were screened and recruited for this study. In the initial time- and dose-dependent studies, we incubated plasma samples from non-smokers with cotinine and ascorbic acid. Changes in cotinine and nicotine levels were quantified using HPLC-PDA. Based on the findings of these experiments, we selected a concentration of 1 µM ascorbic acid and incubated it with plasma samples from 25 smokers for 10 min. A time-dependent study revealed that nicotine was detected in non-smokers' plasma samples after a 10-minute incubation with 28.38 µM of both cotinine and ascorbic acid. In a subsequent dose-dependent study, the maximum concentration of nicotine was observed at 1 µM ascorbic acid. Among the 25 samples of smokers’ plasma, the mean nicotine concentration increased from 0.565 ± 0.196 to 1.937 ± 0.622 µM (P = 0.0081), while cotinine levels decreased from 1.278 ± 0.253 to 0.754 ± 0.137 µM (P = 0.0087). This study conclusively demonstrated that ascorbic acid, at a specified concentration, effectively converts cotinine back into nicotine in smokers' plasma. Importantly, this conversion did not occur in water or in the absence of ascorbic acid in the plasma, indicating enzyme involvement. |
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| format | Article |
| id | doaj.art-a67f3d957f664435b61ca5d1398d9acf |
| institution | Directory Open Access Journal |
| issn | 2667-1379 |
| language | English |
| last_indexed | 2024-04-24T23:22:57Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Advances in Redox Research |
| spelling | doaj.art-a67f3d957f664435b61ca5d1398d9acf2024-03-16T05:09:53ZengElsevierAdvances in Redox Research2667-13792024-04-0110100089Recirculating bioavailable nicotine metabolite using ascorbic acid: A pragmatic approach for treating nicotine dependenceMurugesan Arumugam0Raman Lakshmi Sundaram1Vishal Jayajothi2Manish Arul3Jerad A Suresh4Sathesh Kumar Kesavan5Department of Pharmacology, Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai 600116, India; Corresponding author.Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai 600116, IndiaDepartment of Pharmacology, Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai 600116, IndiaDepartment of Pharmacology, Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai 600116, IndiaSri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai 600116, IndiaDepartment of Pharmaceutics, Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai 600116, IndiaNicotine undergoes metabolism, converting into the oxidized metabolite cotinine, which can persist in the body for several weeks and potentially lead to fatal conditions, such as cancer. Conventional nicotine replacement therapy provides additional nicotine to the body, thereby increasing the chance of accumulating the toxic metabolite cotinine. Consequently, we proposed a hypothesis: converting cotinine back into nicotine using a suitable reducing agent, such as ascorbic acid, could be a practical approach. This conversion would allow cotinine to be reutilized for its central nervous system effects before its eventual elimination from the body. In the current study, we examined this hypothesis by using plasma samples from smokers. Volunteers (both non-smokers and smokers) were screened and recruited for this study. In the initial time- and dose-dependent studies, we incubated plasma samples from non-smokers with cotinine and ascorbic acid. Changes in cotinine and nicotine levels were quantified using HPLC-PDA. Based on the findings of these experiments, we selected a concentration of 1 µM ascorbic acid and incubated it with plasma samples from 25 smokers for 10 min. A time-dependent study revealed that nicotine was detected in non-smokers' plasma samples after a 10-minute incubation with 28.38 µM of both cotinine and ascorbic acid. In a subsequent dose-dependent study, the maximum concentration of nicotine was observed at 1 µM ascorbic acid. Among the 25 samples of smokers’ plasma, the mean nicotine concentration increased from 0.565 ± 0.196 to 1.937 ± 0.622 µM (P = 0.0081), while cotinine levels decreased from 1.278 ± 0.253 to 0.754 ± 0.137 µM (P = 0.0087). This study conclusively demonstrated that ascorbic acid, at a specified concentration, effectively converts cotinine back into nicotine in smokers' plasma. Importantly, this conversion did not occur in water or in the absence of ascorbic acid in the plasma, indicating enzyme involvement.http://www.sciencedirect.com/science/article/pii/S2667137923000292NicotineCotinineNicotine withdrawal effectNicotine replacement therapyAscorbic acidNicotine addiction |
| spellingShingle | Murugesan Arumugam Raman Lakshmi Sundaram Vishal Jayajothi Manish Arul Jerad A Suresh Sathesh Kumar Kesavan Recirculating bioavailable nicotine metabolite using ascorbic acid: A pragmatic approach for treating nicotine dependence Advances in Redox Research Nicotine Cotinine Nicotine withdrawal effect Nicotine replacement therapy Ascorbic acid Nicotine addiction |
| title | Recirculating bioavailable nicotine metabolite using ascorbic acid: A pragmatic approach for treating nicotine dependence |
| title_full | Recirculating bioavailable nicotine metabolite using ascorbic acid: A pragmatic approach for treating nicotine dependence |
| title_fullStr | Recirculating bioavailable nicotine metabolite using ascorbic acid: A pragmatic approach for treating nicotine dependence |
| title_full_unstemmed | Recirculating bioavailable nicotine metabolite using ascorbic acid: A pragmatic approach for treating nicotine dependence |
| title_short | Recirculating bioavailable nicotine metabolite using ascorbic acid: A pragmatic approach for treating nicotine dependence |
| title_sort | recirculating bioavailable nicotine metabolite using ascorbic acid a pragmatic approach for treating nicotine dependence |
| topic | Nicotine Cotinine Nicotine withdrawal effect Nicotine replacement therapy Ascorbic acid Nicotine addiction |
| url | http://www.sciencedirect.com/science/article/pii/S2667137923000292 |
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