Effects of the CB1 receptor antagonists AM6545 and AM4113 on metabolic syndrome-induced prostatic hyperplasia in rats
Metabolic syndrome (MetS) is a combination of metabolic disorders that can predispose individuals to benign prostatic hyperplasia (BPH). The inhibition of the cannabinoid 1 (CB1) receptor has been used to treat metabolic disorders in animal models. This study reports the use of a peripherally restri...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2023-11-01
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| Series: | Biomolecules & Biomedicine |
| Subjects: | |
| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/9173 |
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| author | Basma G. Eid Thikryat Neamatallah Lenah S. Binmahfouz Amina M. Bagher Abdulmohsin J. Alamoudi Hibah Mubarak Aldawsari Abeer Hanafy Atif Hasan Hany M. El-Bassossy Ashraf B. Abdel-Naim Kiran Vemuri Alexandros Makriyannis |
| author_facet | Basma G. Eid Thikryat Neamatallah Lenah S. Binmahfouz Amina M. Bagher Abdulmohsin J. Alamoudi Hibah Mubarak Aldawsari Abeer Hanafy Atif Hasan Hany M. El-Bassossy Ashraf B. Abdel-Naim Kiran Vemuri Alexandros Makriyannis |
| author_sort | Basma G. Eid |
| collection | DOAJ |
| description | Metabolic syndrome (MetS) is a combination of metabolic disorders that can predispose individuals to benign prostatic hyperplasia (BPH). The inhibition of the cannabinoid 1 (CB1) receptor has been used to treat metabolic disorders in animal models. This study reports the use of a peripherally restricted CB1 antagonist (AM6545) and a neutral CB1 antagonist (AM4113) to improve MetS-related BPH in rats. Animals were divided into three control groups to receive either a normal rodent diet, AM6545, or AM4113. MetS was induced in the fourth, fifth, and sixth groups using a concentrated fructose solution and high-salt diet delivered as food pellets for eight weeks. The fifth and sixth groups were further given AM6545 or AM4113 for additional four weeks. Body and prostate weights were measured and prostate sections were stained with hematoxylin eosin. Cyclin D1, markers of oxidative stress and inflammation, and levels of the endocannabinoids were recorded. BPH in rats with MetS was confirmed through increased prostate weight and index, as well as histopathology. Treatment with either AM6545 or AM4113 significantly decreased prostate weight, improved prostate histology, and reduced cyclin D1 expression compared with the MetS group. Groups treated with CB1 antagonists experienced reduced lipid peroxidation, recovered glutathione depletion, restored catalase activity, and had lower inflammatory markers interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α). MetS rats treated with either AM6545 or AM4113 showed reduced concentrations of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the prostate compared with the MetS group. In conclusion, the CB1 antagonists AM6545 and AM4113 protect against MetS-induced BPH through their anti-proliferative, antioxidant, and anti-inflammatory effects.
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| first_indexed | 2024-04-24T23:40:28Z |
| format | Article |
| id | doaj.art-bf26427057b54474941cbe5c795699b5 |
| institution | Directory Open Access Journal |
| issn | 2831-0896 2831-090X |
| language | English |
| last_indexed | 2024-04-24T23:40:28Z |
| publishDate | 2023-11-01 |
| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
| record_format | Article |
| series | Biomolecules & Biomedicine |
| spelling | doaj.art-bf26427057b54474941cbe5c795699b52024-03-15T13:22:24ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2023-11-0123610.17305/bb.2023.9173Effects of the CB1 receptor antagonists AM6545 and AM4113 on metabolic syndrome-induced prostatic hyperplasia in ratsBasma G. Eid0https://orcid.org/0000-0002-8244-1242Thikryat Neamatallah1https://orcid.org/0000-0002-2762-7108Lenah S. Binmahfouz2https://orcid.org/0000-0002-5142-0588Amina M. Bagher3https://orcid.org/0000-0002-1850-5686Abdulmohsin J. Alamoudi4https://orcid.org/0000-0002-9028-8225Hibah Mubarak Aldawsari5Abeer Hanafy6Atif Hasan7Hany M. El-Bassossy8https://orcid.org/0000-0002-6838-6945Ashraf B. Abdel-Naim9https://orcid.org/0000-0002-0400-9075Kiran Vemuri10Alexandros Makriyannis11Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, EgyptDepartment of Anatomy and Embryology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaCenter for Drug Discovery, Northeastern University, Boston, MA, USACenter for Drug Discovery, Northeastern University, Boston, MA, USA; Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, MA, USAMetabolic syndrome (MetS) is a combination of metabolic disorders that can predispose individuals to benign prostatic hyperplasia (BPH). The inhibition of the cannabinoid 1 (CB1) receptor has been used to treat metabolic disorders in animal models. This study reports the use of a peripherally restricted CB1 antagonist (AM6545) and a neutral CB1 antagonist (AM4113) to improve MetS-related BPH in rats. Animals were divided into three control groups to receive either a normal rodent diet, AM6545, or AM4113. MetS was induced in the fourth, fifth, and sixth groups using a concentrated fructose solution and high-salt diet delivered as food pellets for eight weeks. The fifth and sixth groups were further given AM6545 or AM4113 for additional four weeks. Body and prostate weights were measured and prostate sections were stained with hematoxylin eosin. Cyclin D1, markers of oxidative stress and inflammation, and levels of the endocannabinoids were recorded. BPH in rats with MetS was confirmed through increased prostate weight and index, as well as histopathology. Treatment with either AM6545 or AM4113 significantly decreased prostate weight, improved prostate histology, and reduced cyclin D1 expression compared with the MetS group. Groups treated with CB1 antagonists experienced reduced lipid peroxidation, recovered glutathione depletion, restored catalase activity, and had lower inflammatory markers interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α). MetS rats treated with either AM6545 or AM4113 showed reduced concentrations of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the prostate compared with the MetS group. In conclusion, the CB1 antagonists AM6545 and AM4113 protect against MetS-induced BPH through their anti-proliferative, antioxidant, and anti-inflammatory effects. https://www.bjbms.org/ojs/index.php/bjbms/article/view/9173AM6545AM4113prostatecannabinoid antagonistmetabolic syndrome (MetS) |
| spellingShingle | Basma G. Eid Thikryat Neamatallah Lenah S. Binmahfouz Amina M. Bagher Abdulmohsin J. Alamoudi Hibah Mubarak Aldawsari Abeer Hanafy Atif Hasan Hany M. El-Bassossy Ashraf B. Abdel-Naim Kiran Vemuri Alexandros Makriyannis Effects of the CB1 receptor antagonists AM6545 and AM4113 on metabolic syndrome-induced prostatic hyperplasia in rats Biomolecules & Biomedicine AM6545 AM4113 prostate cannabinoid antagonist metabolic syndrome (MetS) |
| title | Effects of the CB1 receptor antagonists AM6545 and AM4113 on metabolic syndrome-induced prostatic hyperplasia in rats |
| title_full | Effects of the CB1 receptor antagonists AM6545 and AM4113 on metabolic syndrome-induced prostatic hyperplasia in rats |
| title_fullStr | Effects of the CB1 receptor antagonists AM6545 and AM4113 on metabolic syndrome-induced prostatic hyperplasia in rats |
| title_full_unstemmed | Effects of the CB1 receptor antagonists AM6545 and AM4113 on metabolic syndrome-induced prostatic hyperplasia in rats |
| title_short | Effects of the CB1 receptor antagonists AM6545 and AM4113 on metabolic syndrome-induced prostatic hyperplasia in rats |
| title_sort | effects of the cb1 receptor antagonists am6545 and am4113 on metabolic syndrome induced prostatic hyperplasia in rats |
| topic | AM6545 AM4113 prostate cannabinoid antagonist metabolic syndrome (MetS) |
| url | https://www.bjbms.org/ojs/index.php/bjbms/article/view/9173 |
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