Drug Repurposing of Metformin for the Treatment of Haloperidol-Related Behavior Disorders and Oxidative Stress: A Preliminary Study
A particular attribute of the brain lies in the ability to learn, acquire information from the environment, and utilize the learned information. Previous research has noted that various factors (e.g., age, stress, anxiety, pathological issues), including antipsychotic medications, affect the brain a...
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MDPI AG
2024-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/16/3/403 |
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| author | George Jîtcă Zsolt Gáll Carmen-Maria Jîtcă Mădălina-Georgiana Buț Erzsébet Májai |
| author_facet | George Jîtcă Zsolt Gáll Carmen-Maria Jîtcă Mădălina-Georgiana Buț Erzsébet Májai |
| author_sort | George Jîtcă |
| collection | DOAJ |
| description | A particular attribute of the brain lies in the ability to learn, acquire information from the environment, and utilize the learned information. Previous research has noted that various factors (e.g., age, stress, anxiety, pathological issues), including antipsychotic medications, affect the brain and memory. The current study aimed to reveal the effects of chronic metformin treatment on the cognitive performance of rats and on commonly measured markers for oxidative stress. Wistar male rats (n = 40) were randomly divided into four groups: CTR (n = 10)–control group, METF (n = 10)–animals receiving metformin 500 mg/kg, HAL (n = 10)–animals receiving haloperidol 2 mg/kg, and HALMETF (n = 10)–animals receiving haloperidol 2 mg/kg and metformin 500 mg/kg. The medication was administered daily by oral gavage for 40 days. Memory and learning were assessed using the Morris Water Maze (MWM) test. At the end of the MWM, the rodents were decapitated under anesthesia, and the brain and blood samples were assayed by liquid chromatography for markers of oxidative stress (malondialdehyde, MDA, reduced/oxidized glutathione ratio, GSH/GSSG). The quantification of brain-derived neurotrophic factor (BDNF) was performed using the conventional sandwich ELISA technique. In the HALMETF group, metformin attenuated the negative effects of haloperidol. Brain and plasma MDA levels increased in the HAL group. Brain and plasma GSH/GSSG ratios and BDNF levels did not reveal any differences between groups. In conclusion, metformin treatment limits the deleterious cognitive effects of haloperidol. The effect on oxidative stress markers may also point toward an antioxidant-like effect of metformin, but this needs further tests for confirmation. |
| first_indexed | 2024-04-24T17:54:52Z |
| format | Article |
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| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-24T17:54:52Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-3f5cd7c72a894cb38583686b2467ceeb2024-03-27T13:59:49ZengMDPI AGPharmaceutics1999-49232024-03-0116340310.3390/pharmaceutics16030403Drug Repurposing of Metformin for the Treatment of Haloperidol-Related Behavior Disorders and Oxidative Stress: A Preliminary StudyGeorge Jîtcă0Zsolt Gáll1Carmen-Maria Jîtcă2Mădălina-Georgiana Buț3Erzsébet Májai4Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540139 Târgu Mureș, RomaniaDepartment of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540139 Târgu Mureș, RomaniaDoctoral School of Medicine and Pharmacy, Institution Organizing Doctor’s Degree University Studies, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540139 Târgu Mureș, RomaniaDepartment of Biochemistry, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540139 Târgu Mureș, RomaniaDepartment of Toxicology and Biopharmacy, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540139 Târgu Mureș, RomaniaA particular attribute of the brain lies in the ability to learn, acquire information from the environment, and utilize the learned information. Previous research has noted that various factors (e.g., age, stress, anxiety, pathological issues), including antipsychotic medications, affect the brain and memory. The current study aimed to reveal the effects of chronic metformin treatment on the cognitive performance of rats and on commonly measured markers for oxidative stress. Wistar male rats (n = 40) were randomly divided into four groups: CTR (n = 10)–control group, METF (n = 10)–animals receiving metformin 500 mg/kg, HAL (n = 10)–animals receiving haloperidol 2 mg/kg, and HALMETF (n = 10)–animals receiving haloperidol 2 mg/kg and metformin 500 mg/kg. The medication was administered daily by oral gavage for 40 days. Memory and learning were assessed using the Morris Water Maze (MWM) test. At the end of the MWM, the rodents were decapitated under anesthesia, and the brain and blood samples were assayed by liquid chromatography for markers of oxidative stress (malondialdehyde, MDA, reduced/oxidized glutathione ratio, GSH/GSSG). The quantification of brain-derived neurotrophic factor (BDNF) was performed using the conventional sandwich ELISA technique. In the HALMETF group, metformin attenuated the negative effects of haloperidol. Brain and plasma MDA levels increased in the HAL group. Brain and plasma GSH/GSSG ratios and BDNF levels did not reveal any differences between groups. In conclusion, metformin treatment limits the deleterious cognitive effects of haloperidol. The effect on oxidative stress markers may also point toward an antioxidant-like effect of metformin, but this needs further tests for confirmation.https://www.mdpi.com/1999-4923/16/3/403oxidative stresscognitionmetforminmalondialdehydeglutathione |
| spellingShingle | George Jîtcă Zsolt Gáll Carmen-Maria Jîtcă Mădălina-Georgiana Buț Erzsébet Májai Drug Repurposing of Metformin for the Treatment of Haloperidol-Related Behavior Disorders and Oxidative Stress: A Preliminary Study Pharmaceutics oxidative stress cognition metformin malondialdehyde glutathione |
| title | Drug Repurposing of Metformin for the Treatment of Haloperidol-Related Behavior Disorders and Oxidative Stress: A Preliminary Study |
| title_full | Drug Repurposing of Metformin for the Treatment of Haloperidol-Related Behavior Disorders and Oxidative Stress: A Preliminary Study |
| title_fullStr | Drug Repurposing of Metformin for the Treatment of Haloperidol-Related Behavior Disorders and Oxidative Stress: A Preliminary Study |
| title_full_unstemmed | Drug Repurposing of Metformin for the Treatment of Haloperidol-Related Behavior Disorders and Oxidative Stress: A Preliminary Study |
| title_short | Drug Repurposing of Metformin for the Treatment of Haloperidol-Related Behavior Disorders and Oxidative Stress: A Preliminary Study |
| title_sort | drug repurposing of metformin for the treatment of haloperidol related behavior disorders and oxidative stress a preliminary study |
| topic | oxidative stress cognition metformin malondialdehyde glutathione |
| url | https://www.mdpi.com/1999-4923/16/3/403 |
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