Fatma Mostafa, Eman M Mantawy, Riham S Said, Samar S Azab, Ebtehal El-Demerdash
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引用次数: 0
Abstract
Rationale: One of the most debilitating drawbacks of cisplatin chemotherapy is neurotoxicity which elicits memory impairment and cognitive dysfunction (chemobrain). This is primarily triggered by oxidative stress and inflammation. Captopril, an angiotensin-converting enzyme inhibitor, has been reported as a neuroprotective agent owing to its antioxidant and anti-inflammatory effects.
Objective: We examined the possible neuroprotective effect of captopril against cisplatin-induced neurological and behavioral abnormalities in rats.
Methods: Chemobrain was induced in rats by cisplatin (5 mg/kg, i.p.) on the 7th and 14th days of the study while captopril was administered orally (25 mg/kg) daily for three weeks. The effects of captopril were assessed by performing behavioral tests, histological examination, and evaluation of oxidative stress and inflammatory markers.
Results: Cisplatin caused learning/memory dysfunction assessed by passive avoidance and Y-maze tests, decline in locomotion, and rotarod motor balance loss which were further verified by neurodegeneration observed in histological examination. Also, cisplatin aggravated oxidative stress by elevating lipid peroxidation (MDA) levels and diminishing catalase activity. Moreover, cisplatin upregulated the neuroinflammatory markers (TNF, IL-6, GFAP, and NF-κB). Captopril successfully ameliorated cisplatin damage on the levels of neurobehavioral and histopathological changes. Mechanistically, captopril significantly diminished MDA production and preserved catalase antioxidant activity. Captopril also counteracted neuroinflammation through inhibiting NF-κB and its downstream proinflammatory cytokines besides repressing astrocyte activity by reducing GFAP expression.
Conclusion: Our findings revealed that captopril could abrogate cisplatin neurotoxicity via reducing oxidative stress and neuroinflammation thus enhancing cognitive and behavioral performance. This could suggest the repurposing of captopril as a neuroprotective agent, especially in hypertensive cancer patients receiving cisplatin.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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