Orlistat Mitigates Oxidative Stress-Linked Myocardial Damage via NF-κβ- and Caspase-Dependent Activities in Obese Rats
Oxidative stress contributes to major complications of obesity. This study intended to identify whether orlistat could mitigate myocardial damage in obese animal models. The tested rats were divided into two groups and fed either with normal chow (<i>n</i> = 6 per group) or with a high-f...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/18/10266 |
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| author | Zaidatul Akmal Othman Zaida Zakaria Joseph Bagi Suleiman Khairul Mohd Fadzli Mustaffa Nur Asyilla Che Jalil Wan Syaheedah Wan Ghazali Ninie Nadia Zulkipli Mahaneem Mohamed |
| author_facet | Zaidatul Akmal Othman Zaida Zakaria Joseph Bagi Suleiman Khairul Mohd Fadzli Mustaffa Nur Asyilla Che Jalil Wan Syaheedah Wan Ghazali Ninie Nadia Zulkipli Mahaneem Mohamed |
| author_sort | Zaidatul Akmal Othman |
| collection | DOAJ |
| description | Oxidative stress contributes to major complications of obesity. This study intended to identify whether orlistat could mitigate myocardial damage in obese animal models. The tested rats were divided into two groups and fed either with normal chow (<i>n</i> = 6 per group) or with a high-fat diet (HFD) for 6 weeks to induce obesity (<i>n</i> = 12 per group). Obese rats were further subjected to treatment either with distilled water (OB group) or orlistat 10 mg/kg/day (OB + OR group). Key indices of oxidative stress, inflammation, and apoptosis were assessed using an immunohistochemical-based technique and real-time PCR. The OB group showed significant increases of oxidative stress markers (TBARs and PCO), with significant decreases of anti-oxidant markers (Nrf2, SOD, CAT, and GPx). Furthermore, mRNA expression of pro-inflammatory markers (TNF-α and NF-κβ) and pro-apoptosis markers (Bax, Caspase-3, Caspase-8, and Caspase-9) were significantly upregulated in the OB group. Obese rats developed pathological changes of myocardial damages as evidenced by the presence of myocardial hypertrophy and inflammatory cells infiltration. Orlistat dampened the progression of myocardial damage in obese rats by ameliorating the oxidative stress, and by inhibiting NF-κβ pathway and caspase-dependent cell apoptosis. Our study proposed that orlistat could potentially mitigate oxidative stress-linked myocardial damage by mitigating inflammation and apoptosis, thus rationalizing its medical usage. |
| first_indexed | 2024-03-09T23:48:51Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:48:51Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-98b90e203294483686138f81b642d6212023-11-23T16:38:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181026610.3390/ijms231810266Orlistat Mitigates Oxidative Stress-Linked Myocardial Damage via NF-κβ- and Caspase-Dependent Activities in Obese RatsZaidatul Akmal Othman0Zaida Zakaria1Joseph Bagi Suleiman2Khairul Mohd Fadzli Mustaffa3Nur Asyilla Che Jalil4Wan Syaheedah Wan Ghazali5Ninie Nadia Zulkipli6Mahaneem Mohamed7Unit of Physiology, Faculty of Medicine, Universiti Sultan Zainal Abidin, Kuala Terengganu 20400, Terengganu, MalaysiaDepartment of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaDepartment of Science Laboratory Technology, Akanu Ibiam Federal Polytechnic, Unwana P.M.B. 1007, Afikpo, Ebonyi State, NigeriaInstitute for Research in Molecular Medicine, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaDepartment of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaDepartment of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaDepartment of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaDepartment of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaOxidative stress contributes to major complications of obesity. This study intended to identify whether orlistat could mitigate myocardial damage in obese animal models. The tested rats were divided into two groups and fed either with normal chow (<i>n</i> = 6 per group) or with a high-fat diet (HFD) for 6 weeks to induce obesity (<i>n</i> = 12 per group). Obese rats were further subjected to treatment either with distilled water (OB group) or orlistat 10 mg/kg/day (OB + OR group). Key indices of oxidative stress, inflammation, and apoptosis were assessed using an immunohistochemical-based technique and real-time PCR. The OB group showed significant increases of oxidative stress markers (TBARs and PCO), with significant decreases of anti-oxidant markers (Nrf2, SOD, CAT, and GPx). Furthermore, mRNA expression of pro-inflammatory markers (TNF-α and NF-κβ) and pro-apoptosis markers (Bax, Caspase-3, Caspase-8, and Caspase-9) were significantly upregulated in the OB group. Obese rats developed pathological changes of myocardial damages as evidenced by the presence of myocardial hypertrophy and inflammatory cells infiltration. Orlistat dampened the progression of myocardial damage in obese rats by ameliorating the oxidative stress, and by inhibiting NF-κβ pathway and caspase-dependent cell apoptosis. Our study proposed that orlistat could potentially mitigate oxidative stress-linked myocardial damage by mitigating inflammation and apoptosis, thus rationalizing its medical usage.https://www.mdpi.com/1422-0067/23/18/10266orlistatobesityoxidative stressinflammationapoptosis |
| spellingShingle | Zaidatul Akmal Othman Zaida Zakaria Joseph Bagi Suleiman Khairul Mohd Fadzli Mustaffa Nur Asyilla Che Jalil Wan Syaheedah Wan Ghazali Ninie Nadia Zulkipli Mahaneem Mohamed Orlistat Mitigates Oxidative Stress-Linked Myocardial Damage via NF-κβ- and Caspase-Dependent Activities in Obese Rats International Journal of Molecular Sciences orlistat obesity oxidative stress inflammation apoptosis |
| title | Orlistat Mitigates Oxidative Stress-Linked Myocardial Damage via NF-κβ- and Caspase-Dependent Activities in Obese Rats |
| title_full | Orlistat Mitigates Oxidative Stress-Linked Myocardial Damage via NF-κβ- and Caspase-Dependent Activities in Obese Rats |
| title_fullStr | Orlistat Mitigates Oxidative Stress-Linked Myocardial Damage via NF-κβ- and Caspase-Dependent Activities in Obese Rats |
| title_full_unstemmed | Orlistat Mitigates Oxidative Stress-Linked Myocardial Damage via NF-κβ- and Caspase-Dependent Activities in Obese Rats |
| title_short | Orlistat Mitigates Oxidative Stress-Linked Myocardial Damage via NF-κβ- and Caspase-Dependent Activities in Obese Rats |
| title_sort | orlistat mitigates oxidative stress linked myocardial damage via nf κβ and caspase dependent activities in obese rats |
| topic | orlistat obesity oxidative stress inflammation apoptosis |
| url | https://www.mdpi.com/1422-0067/23/18/10266 |
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