Protective Effect of Galantamine against Doxorubicin-Induced Neurotoxicity
Background and aims: Doxorubicin (DOX) causes cognitive impairment (chemobrain) in patients with cancer. While DOX damages the cholinergic system, few studies have focused on the protective effects of cholinergic function on chemobrain. The acetylcholinesterase inhibitor galantamine (GAL) demonstrat...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/13/6/971 |
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| author | Rawan S. Alsikhan Maha A. Aldubayan Ibtesam S. Almami Ahmad H. Alhowail |
| author_facet | Rawan S. Alsikhan Maha A. Aldubayan Ibtesam S. Almami Ahmad H. Alhowail |
| author_sort | Rawan S. Alsikhan |
| collection | DOAJ |
| description | Background and aims: Doxorubicin (DOX) causes cognitive impairment (chemobrain) in patients with cancer. While DOX damages the cholinergic system, few studies have focused on the protective effects of cholinergic function on chemobrain. The acetylcholinesterase inhibitor galantamine (GAL) demonstrates neuroprotective properties. We investigated the mechanisms associated with DOX-induced cognitive impairments and the potential protective role of GAL in preventing chemobrain. Main methods: Female Wistar rats were divided into control, DOX, GAL, and DOX + GAL groups. The rats in the DOX group were administered DOX (5 mg/kg intraperitoneally twice weekly for two weeks), while those in the GAL group were orally administered GAL (2.5 mg/kg) via oral gavage once daily for 15 days. The combination group (DOX + GAL) received GAL (once daily) and DOX (two times per week) concurrently. The body weights and survival rates were monitored daily. The animals were subjected to behavioral tests to assess the memory function followed by the biochemical estimation of inflammatory markers, including tumor necrosis factor-α (TNF-<i>α</i>), interleukine-1β (IL-1<i>β</i>), and interleukine-6 (IL-6) in rat brain tissue and RT-qPCR. Key findings: DOX caused a reduction in the body weight and survival rate, which was alleviated by GAL concomitant treatment with DOX (DOX + GAL). These groups had reduced body weights and survival rates. DOX-treated animals exhibited an impairment of short-term spatial working memory, manifested as a behavioral alteration in the Y-maze test, the novel object recognition (NOR) test, and the elevated plus-maze (EPM) test. Concurrent treatment with GAL (DOX + GAL) showed improved memory function, as evidenced by an increase in the number of entries and time spent in the novel arm, the time spent exploring the novel object, and the transfer latency in the Y-maze, NOR test, and EPM test, respectively. These findings were also supported by biochemical observations showing the reversal of DOX-induced changes in IL-1<i>β</i>, IL-6, and TNF-<i>α</i>, as well as their relative expression of mRNA in brain tissue following concurrent GAL treatment. Conclusion: GAL appeared to be a neuroprotective agent against neuroinflammation caused by DOX by reducing inflammatory markers in the brain. |
| first_indexed | 2024-03-11T02:40:57Z |
| format | Article |
| id | doaj.art-9b5f9dbf435643bc83ec4c7fa9c0f25a |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-11T02:40:57Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-9b5f9dbf435643bc83ec4c7fa9c0f25a2023-11-18T09:37:07ZengMDPI AGBrain Sciences2076-34252023-06-0113697110.3390/brainsci13060971Protective Effect of Galantamine against Doxorubicin-Induced NeurotoxicityRawan S. Alsikhan0Maha A. Aldubayan1Ibtesam S. Almami2Ahmad H. Alhowail3Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi ArabiaDepartment of Biology, College of Science, Qassim University, Buraydah 51452, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi ArabiaBackground and aims: Doxorubicin (DOX) causes cognitive impairment (chemobrain) in patients with cancer. While DOX damages the cholinergic system, few studies have focused on the protective effects of cholinergic function on chemobrain. The acetylcholinesterase inhibitor galantamine (GAL) demonstrates neuroprotective properties. We investigated the mechanisms associated with DOX-induced cognitive impairments and the potential protective role of GAL in preventing chemobrain. Main methods: Female Wistar rats were divided into control, DOX, GAL, and DOX + GAL groups. The rats in the DOX group were administered DOX (5 mg/kg intraperitoneally twice weekly for two weeks), while those in the GAL group were orally administered GAL (2.5 mg/kg) via oral gavage once daily for 15 days. The combination group (DOX + GAL) received GAL (once daily) and DOX (two times per week) concurrently. The body weights and survival rates were monitored daily. The animals were subjected to behavioral tests to assess the memory function followed by the biochemical estimation of inflammatory markers, including tumor necrosis factor-α (TNF-<i>α</i>), interleukine-1β (IL-1<i>β</i>), and interleukine-6 (IL-6) in rat brain tissue and RT-qPCR. Key findings: DOX caused a reduction in the body weight and survival rate, which was alleviated by GAL concomitant treatment with DOX (DOX + GAL). These groups had reduced body weights and survival rates. DOX-treated animals exhibited an impairment of short-term spatial working memory, manifested as a behavioral alteration in the Y-maze test, the novel object recognition (NOR) test, and the elevated plus-maze (EPM) test. Concurrent treatment with GAL (DOX + GAL) showed improved memory function, as evidenced by an increase in the number of entries and time spent in the novel arm, the time spent exploring the novel object, and the transfer latency in the Y-maze, NOR test, and EPM test, respectively. These findings were also supported by biochemical observations showing the reversal of DOX-induced changes in IL-1<i>β</i>, IL-6, and TNF-<i>α</i>, as well as their relative expression of mRNA in brain tissue following concurrent GAL treatment. Conclusion: GAL appeared to be a neuroprotective agent against neuroinflammation caused by DOX by reducing inflammatory markers in the brain.https://www.mdpi.com/2076-3425/13/6/971doxorubicingalantamineneuroinflammationcognitive impairmentneuroprotectiveELISA |
| spellingShingle | Rawan S. Alsikhan Maha A. Aldubayan Ibtesam S. Almami Ahmad H. Alhowail Protective Effect of Galantamine against Doxorubicin-Induced Neurotoxicity Brain Sciences doxorubicin galantamine neuroinflammation cognitive impairment neuroprotective ELISA |
| title | Protective Effect of Galantamine against Doxorubicin-Induced Neurotoxicity |
| title_full | Protective Effect of Galantamine against Doxorubicin-Induced Neurotoxicity |
| title_fullStr | Protective Effect of Galantamine against Doxorubicin-Induced Neurotoxicity |
| title_full_unstemmed | Protective Effect of Galantamine against Doxorubicin-Induced Neurotoxicity |
| title_short | Protective Effect of Galantamine against Doxorubicin-Induced Neurotoxicity |
| title_sort | protective effect of galantamine against doxorubicin induced neurotoxicity |
| topic | doxorubicin galantamine neuroinflammation cognitive impairment neuroprotective ELISA |
| url | https://www.mdpi.com/2076-3425/13/6/971 |
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