SİSPLATİN'İN NÖROTOKSİK ETKİSİNE BAĞLI GELİŞEN HİPOKAMPAL NÖRON HASARINA KARŞI MELATONİN NÖROPROTEKTİF ETKİNLİĞİNİN ARAŞTIRILMASI

Year 2021, Volume: 4 Issue: 1, 87 - 93, 30.05.2021

Ümit Ali Malçok , Başak Büyük

https://doi.org/10.52538/iduhes.926453

Cited By: 2

Abstract

Sisplatin yaygın kullanılan ancak yaşam kalitesini düşüren etkileri olan bir antineoplastiktir. Özellikle nörotoksik etkileri, hastaların %70’inde tedavi esnasında veya sonrasında bilişsel bozulmalara yol açmaktadır. Bu çalışmada melatoninin siplatin toksistesini azaltıcı etkinliği araştırıldı. Denek olarak 24 yetişkin erkek Wistar Albino ırkı sıçan kullanılarak 4 grup oluşturuldu. Sıçanlara 1. 5. 9. ve 13. günlerde ve 4 mg/kg dozunda intraperitoneal (ip) sisplatin verilerek nörotoksisite oluşturuldu. Tedavi grubuna ise 13 gün 10 mg/kg/gün dozunda ip melatonin uygulanarak gruplar karşılaştırıldı. 14. günde yapılan sakrifikasyon sonrası hipokampus dokuları alındı. Piknozis ve ödem skorları hesaplanarak sisplatin toksisitesi ve melatoninin etkinliği analiz edildi. Sham grubu ile Mel ve Cisp+Mel grupları arasında piknosis açısından anlamlı fark olmadığı ancak sisplatin verilen grupta belirgin düzeyde piknotik nöron artışı olduğu görüldü (p<0.01). Sisplatin verilen ratlarda hipokampus dokusundaki ödemin belirgin düzeyde arttığı buna karşın melatonin verildiğinde ödem skorlarının istatistiksel olarak anlamlı seviyede düştüğü izlendi (p<0.01). Sisplatin ve melatonin benzer oksidatif ve apoptotik süreçleri zıt yönlerde etkilemektedir. Biz de çalışmamızda melatoninin sisplatin toksisitesi üzerine olan etkilerini inceledik ve melatoninin sisplatinin nörotoksik etkilerine karşı koruyucu etki gösterdiği sonucuna ulaştık. Ulaştığımız bu sonuç yaygın kullanılan bir kemoteropatik olan sisplatin, melatonin ile kombine edilerek kullanıldığında kanser hastalarının daha az nörotoksik yan etkilere maruz kalmasını sağlayacaktır.

Keywords

Sisplatin, melatonin, nörotoksisite, hipokampüs

INVESTIGATION OF THE NEUROPROTECTIVE EFFECT OF MELATONIN ON HIPPOCAMPAL NEURON INJURY DEVELOPING DUE TO THE NEUROTOXIC EFFECT OF CISPLATIN

Abstract

Cisplatin is a widely used antineoplastic agent, but it has side effects that decrease quality of life. Its neurotoxic effects lead to cognitive disorders during or after treatment in 70% of the patients. In this study, the efficiency of melatonin to reduce cisplatin-induced toxicity was investigated. Four subject groups were established using 24 adult male Wistar Albino rats. Neurotoxicity was produced by administering intraperitoneal (ip) cisplatin on the 1st, 5th, 9th and 13th day at a dose of 4 mg/kg. Intraperitoneal melatonin was applied to the treatment group for 13 days at a dose of 10 mg/kg/day and the groups were compared. Following sacrification on the 14th day, hippocampal tissues were excised. Cisplatin toxicity and melatonin efficiency were analyzed by calculating pyknosis and edema scores. It was observed that there was no significant difference between the Sham, Mel and Cisp+Mel groups in terms of pyknosis, but a marked increase in pyknotic neurons occurred in the group which was given cisplatin (p<0.01). It was found that edema in the hippocampal tissue increased markedly in the rats which were given cisplatin, but edema scores statistically significantly decreased when melatonin was given (p<0.01). Cisplatin and melatonin influence the same oxidative and apoptotic processes in opposite directions. In our study, we examined the effects of melatonin on cisplatin-induced toxicity and concluded that melatonin showed protective action against cisplatin-induced neurotoxic effects. Our conclusion indicated that cancer patients would be exposed to fewer neurotoxic side effects when cisplatin, a widely used chemotherapeutic drug, is used in combination with melatonin.

Keywords

Cisplatin, melatonin, neurotoxicity, hippocampus

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