Agomelatine confers neuroprotection against cisplatin-induced hippocampal neurotoxicity
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ORIGINAL ARTICLE
Agomelatine confers neuroprotection against cisplatin-induced hippocampal neurotoxicity Fatma Nihan Cankara 1 & Caner Günaydın 2 Yalçın Erzurumlu 4 & Kanat Gülle 5
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Zülfinaz Betül Çelik 3
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Yasemin Şahin 1
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Şakir Pekgöz 1 &
Received: 7 August 2020 / Accepted: 14 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Neurotoxicity caused by cisplatin is a major obstacle during chemotherapy. Oxidative stress and inflammation are considered the primary mechanism behind neuronal damage which affects the continuing chemotherapy regimen. Agomelatine was recently described as a neuroprotective compound against toxic insults in the nervous systems. It is an analog of the well-known antioxidant and anti-inflammatory compound melatonin and currently used for depression and sleep disturbances. In the current study, we investigated the possible neuroprotective role of agomelatine against cisplatin-induced oxidative, inflammatory, and behavioral alterations in male rats. Our results show that agomelatine prevented cisplatin-induced neurotoxicity in the HT-22 mouse hippocampal neuronal cell line. Additionally, agomelatine treatment inhibited cisplatin-induced behavioral deficits and neuronal integrity in vivo. For the evaluation of the effect of agomelatine on oxidative stress and inflammation, GSH, MDA, TNF, and IL-6 levels were analyzed in HT-22 cells and hippocampal tissues. Agomelatine significantly attenuated oxidative stress and inflammation due to the cisplatin insult in vitro and in vivo. Also, agomelatine treatment ameliorated the neuronal pathology in the hippocampus, which is strongly related to cognition and memory. Taken together, our results indicate that in males, the neuroprotective effect of agomelatine is mediated through its antioxidant and anti-inflammatory actions abrogating functional deficits. Keywords Agomelatine . Cisplatin . Neurotoxicity . Hippocampus . HT-22 cell line . Wistar-albino rat
Introduction Cisplatin is a platinum-based chemotherapeutic agent that was developed in the 1970s. It has been widely used for the treatment of several solid tumors including lung,
* Fatma Nihan Cankara [email protected] 1
Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Isparta 32260, Turkey
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Department of Pharmacology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey
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Department of Medical Biology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey
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Department of Biochemistry, Faculty of Pharmacy, Suleyman Demirel University, Isparta, Turkey
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Department of Histology and Embryology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
testis, skin, ovarian, colorectal, and bladder cancer (Zhu et al. 2016). Nevertheless, cisplatin-induced neurotoxicity in the form of peripheral neuropathy, impaired recognition, tremor, and ataxia are well-defined dose-limiting adverse effects that limit its clinical usefulness. Production of pro-inflammatory cytokines, oxidative stress
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