Antioxidant effect of simvastatin throught oxidative imbalance caused by lisdexamfetamine dimesylate
Open accessAbstract
The present study aims to directly investigate the behavioral and antioxidant effects of simvastatin in a model of bipolar mania induced by lisdexamfetamine dimesylate. Wistar rats were treated for 30 days with simvastatin. On the 24th day after the start of treatment, each rat was administered lisdexamfetamine dimesylate for 7 days. The results suggest that simvastatin combined with lisdexamfetamine dimesylate induced a significant increased locomotion and lisdexamfetamine dimesylate administration causes an oxidative imbalance determined by an increment in lipid peroxidation, protein oxidation and alterations in the activities of antioxidant enzymes in brain areas; moreover, in the presence of simvastatin, most of these effects were prevented. These findings contribute to a better understanding of the critical roles of lisdexamfetamine dimesylate in the treatment of neuropsychiatric disorders, associated with increased oxidative stress and changes in antioxidant enzymatic defense. In view of the central role played by lisdexamfetamine dimesylate, the established antioxidant effect of simvastatin therapy is of major interest.
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Two studies have shown that the levels of these enzymes were decreased by LDX in neuropsychiatric disorder models.
“In this sense, two studies have shown that the levels of these enzymes were decreased by LDX in neuropsychiatric disorder models [225, 226].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [225]
The paper studies an LDX-induced rat model of bipolar mania. Its SOD assay discussion reports decreased CAT activity in the hippocampus and cerebral cortex and decreased SOD activity in the cerebellum. But it also reports increased SOD and GSH-Px activity in the hippocampus and cerebral cortex, so the unqualified claim that these enzymes decreased overstates its findings (page unavailable in our copy). (LLM, conf=0.88)
Experimental — accuracy not yet measuredLDX increases the thiobarbituric acid-reactive substances in the cerebellum, hippocampus and cerebral cortex, although its MoA is unknown.
“LDX increases the thiobarbituric acid-reactive substances in the cerebellum, hippocampus and cerebral cortex, although its MoA is unknown [225].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [225]
The TBARS section reports that repeated LDX exposure increased TBARS in the cerebellum, hippocampus and cerebral cortex of rats. The discussion says the mechanisms responsible for LDX-induced oxidative stress have not been fully identified, but suggests dopamine metabolism and oxidation as a possible mechanism. Calling LDX’s mode of action simply “unknown” overstates that qualification. (LLM, conf=0.85)
Experimental — accuracy not yet measuredLDX causes oxidative imbalance through increased lipid peroxidation, protein oxidation and alterations in the activity of antioxidant enzymes in some brain areas.
“LDX causes oxidative imbalance through increased lipid peroxidation, protein oxidation and alterations in the activity of antioxidant enzymes in some brain areas [225].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [225]
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“In this sense, two studies have shown that the levels of these enzymes were decreased by LDX in neuropsychiatric disorder models [225, 226].”
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- Authors
- Eger, G. A., Ferreira, V. V., Batista, C. R., Bonde, H., Lima, D. D. D., Wyse, A. T. S., Cruz, J. N. D., Rodrigues, A. F., Magro, D. D. D., & Cruz, J. G. P. D.
- Affiliations
- Universidade Regional de Blumenau (BR)
- Universidade da Região de Joinville (BR)
- Universidade Federal do Rio Grande do Sul, Brasil
- Venue
- Anais da Academia Brasileira de Ciências
- Publisher
- FapUNIFESP (SciELO)
- Published
- 2016-02-05
- Volume
- 88
- Issue
- 1
- Pages
- 335-348
- ISSN
- 0001-3765 (ISSN-L)
- 1678-2690
- OpenAlex
- W2324663504
- Cited by
- 13
- References
- 55
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2018: 1 · 2017: 2
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Anais da Academia Brasileira de Ciências (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
- Americanae (AECID Library) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Redalyc (Universidad Autónoma del Estado de México) (submittedVersion)
- Funders
- Universidade Regional de Blumenau
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- simvastatin, lisdexamfetamine dimesylate, oxidative stress, antioxidant enzymes, lipid peroxidation, protein oxidation, bipolar mania, locomotor activity, brain, statins
- MeSH terms
- Lisdexamfetamine Dimesylate, Central Nervous System Stimulants, Animals, Antioxidants, Behavior, Animal, Bipolar Disorder, Male, Lipid Peroxidation, Rats, Wistar, Oxidative Stress, Antimanic Agents, Simvastatin, Rats
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