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抗生素与神经系统——抗生素治疗的真面目,是 Dr. Jekyll(神经毒性)还是 Mr. Hyde(神经保护)?

Antibiotics and the Nervous System-Which Face of Antibiotic Therapy Is Real, Dr. Jekyll (Neurotoxicity) or Mr. Hyde (Neuroprotection)?

机构信息

Department of Clinical Pharmacology, Wroclaw Medical University, 50-556 Wroclaw, Poland.

Clinical Pharmacy Service, Jan Mikulicz-Radecki University Clinical Hospital, 50-556 Wroclaw, Poland.

出版信息

Molecules. 2021 Dec 9;26(24):7456. doi: 10.3390/molecules26247456.

Abstract

Antibiotics as antibacterial drugs have saved many lives, but have also become a victim of their own success. Their widespread abuse reduces their anti-infective effectiveness and causes the development of bacterial resistance. Moreover, irrational antibiotic therapy contributes to gastrointestinal dysbiosis, that increases the risk of the development of many diseases, including neurological and psychiatric. One of the potential options for restoring homeostasis is the use of oral antibiotics that are poorly absorbed from the gastrointestinal tract (e.g., rifaximin alfa). Thus, antibiotic therapy may exert neurological or psychiatric adverse drug reactions which are often considered to be overlooked and undervalued issues. Drug-induced neurotoxicity is mostly observed after beta-lactams and quinolones. Penicillin may produce a wide range of neurological dysfunctions, including encephalopathy, behavioral changes, myoclonus or seizures. Their pathomechanism results from the disturbances of gamma-aminobutyric acid-GABA transmission (due to the molecular similarities between the structure of the β-lactam ring and GABA molecule) and impairment of the functioning of benzodiazepine receptors (BZD). However, on the other hand, antibiotics have also been studied for their neuroprotective properties in the treatment of neurodegenerative and neuroinflammatory processes (e.g., Alzheimer's or Parkinson's diseases). Antibiotics may, therefore, become promising elements of multi-targeted therapy for these entities.

摘要

抗生素作为抗菌药物挽救了许多生命,但也成为了自身成功的受害者。它们的广泛滥用降低了它们的抗感染效果,并导致细菌耐药性的发展。此外,不合理的抗生素治疗会导致胃肠道菌群失调,从而增加许多疾病(包括神经和精神疾病)的发病风险。恢复体内平衡的潜在选择之一是使用口服抗生素,这些抗生素从胃肠道吸收不良(例如,利福昔明阿尔法)。因此,抗生素治疗可能会引起神经或精神不良反应药物反应,这些反应通常被认为是被忽视和低估的问题。药物引起的神经毒性主要发生在β-内酰胺类和喹诺酮类之后。青霉素可能产生广泛的神经功能障碍,包括脑病、行为改变、肌阵挛或癫痫发作。它们的发病机制是由于γ-氨基丁酸-GABA 传递的紊乱(由于β-内酰胺环和 GABA 分子的结构之间存在分子相似性)和苯二氮䓬受体(BZD)功能障碍。然而,另一方面,抗生素也因其在治疗神经退行性和神经炎症过程中的神经保护特性而受到研究(例如,阿尔茨海默病或帕金森病)。因此,抗生素可能成为这些疾病多靶点治疗的有希望的元素。

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