Ezgi Eroglu1, Cigdem Cengelli Unel2, Nusin Harmanci2, Kevser Erol3, Neziha Senem Ari4, Orhan Ozatik5. 1. Department of Pharmacology, Faculty of Pharmacy, Lokman Hekim University, Ankara, Turkey; Department of Medical Pharmacology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey. Electronic address: ezgbzkrt@gmail.com. 2. Department of Medical Pharmacology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey. 3. Department of Medical Pharmacology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey; Department of Medical Pharmacology, Faculty of Medicine, Bahcesehir University, Istanbul, Turkey. 4. Department of Histology and Embryology, Evliya Celebi Education and Research Hospital, Kutahya Health Sciences University, Kutahya, Turkey. 5. Department of Histology and Embryology, Faculty of Medicine, Kutahya Health Sciences University, Kutahya, Turkey.
Abstract
AIM OF THE STUDY: Cisplatin is a platinum-derived chemotherapeutic agent commonly used in the treatment of various tumors. Ototoxicity, nephrotoxicity, and peripheral neuropathy are the most common side effects of this drug. 2-Aminoethoxydiphenyl borate (2-APB), boron- containing compound, has some protective effects against various tissue damage. The present study aimed to investigate the potential protective effects of 2-APB on in vitro and in vivo cisplatin-induced neurotoxicity. MATERIALS AND METHODS: MTT assay was used to determine cell viability in DRG cells. Peripheral neuropathy was induced in forty male Sprague-Dawley rats (200-250g) by administering cisplatin (3 mg/kg/week) intraperitoneally (i.p) for five weeks. 2-APB (2, 4, and 8 mg/kg, i.p) was administered. Mechanical allodynia, thermal hyperalgesia, cold allodynia, mechanical stimuli, motor coordination, and locomotor activity tests were performed. DRG cells and sciatic nerves were analyzed histologically. NGF, BDNF, TNF-α, GSH, MDA, and LDH levels were investigated in rat DRG tissue homogenates. RESULTS: Our results revealed that 2-APB ameliorated cisplatin-induced neurotoxicity by improving mechanical and cold allodynia and motor coordination impairment. It also reduced cisplatin-induced structural toxicity in peripheral tissues. CONCLUSION: These findings demonstrated that 2-APB could be considered as a potential therapeutic strategy for the treatment of cisplatin-induced peripheral neuropathy.
AIM OF THE STUDY: Cisplatin is a platinum-derived chemotherapeutic agent commonly used in the treatment of various tumors. Ototoxicity, nephrotoxicity, and peripheral neuropathy are the most common side effects of this drug. 2-Aminoethoxydiphenyl borate (2-APB), boron- containing compound, has some protective effects against various tissue damage. The present study aimed to investigate the potential protective effects of 2-APB on in vitro and in vivo cisplatin-induced neurotoxicity. MATERIALS AND METHODS: MTT assay was used to determine cell viability in DRG cells. Peripheral neuropathy was induced in forty male Sprague-Dawley rats (200-250g) by administering cisplatin (3 mg/kg/week) intraperitoneally (i.p) for five weeks. 2-APB (2, 4, and 8 mg/kg, i.p) was administered. Mechanical allodynia, thermal hyperalgesia, cold allodynia, mechanical stimuli, motor coordination, and locomotor activity tests were performed. DRG cells and sciatic nerves were analyzed histologically. NGF, BDNF, TNF-α, GSH, MDA, and LDH levels were investigated in rat DRG tissue homogenates. RESULTS: Our results revealed that 2-APB ameliorated cisplatin-induced neurotoxicity by improving mechanical and cold allodynia and motor coordination impairment. It also reduced cisplatin-induced structural toxicity in peripheral tissues. CONCLUSION: These findings demonstrated that 2-APB could be considered as a potential therapeutic strategy for the treatment of cisplatin-induced peripheral neuropathy.
Authors: Rocío Fernández-Serra; Emma Martínez-Alonso; Alberto Alcázar; Mourad Chioua; José Marco-Contelles; Ricardo Martínez-Murillo; Milagros Ramos; Gustavo V Guinea; Daniel González-Nieto Journal: Int J Mol Sci Date: 2022-07-04 Impact factor: 6.208