Effect of elamipretide and methylprednisolone treatment on optic nerve, retina and brain damage in a methanol poisoning model: biochemical and histopathological evaluation.

IF 1.6 4区 医学 Q3 OPHTHALMOLOGY Cutaneous and Ocular Toxicology Pub Date : 2024-11-27 DOI:10.1080/15569527.2024.2430241
Ozlem Bulbul, Renad Mammadov, Bahadır Suleyman, Ali Kulaber, Yunus Karaca, Huseyin Yaman, Engin Yenilmez, Aynur Sahin, Vildan Ozer
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Abstract

Purpose: This study aimed to biochemically and histopathologically evaluate the protective and therapeutic effects of elamipretide and methylprednisolone on methanol poisoning-induced brain, optic nerve, and retinal toxicity.

Method: In this study, 40 male Wistar Albino rats were divided into six groups: healthy control (HC), methotrexate (MTX, 0.3 mg/kg/d for 7 d), methotrexate + methanol (MTX-M, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8), methotrexate + methanol + methylprednisolone (MTX-M-MPZ, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + MPZ 1 mg/kg/d for 3 d), methotrexate + methanol + elamipretide (MTX-M-E, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + elamipretide 5 mg/kg/d for 3 d), and methotrexate + methanol + methylprednisolone + elamipretide (MTX-M-MPZ-E, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + MPZ 1 mg/kg/d + Elamipretide 5 mg/kg/d for 3 d). The rats were euthanized 8 h after the last drug administration. Histopathological and biochemical evaluations were performed on serum, caudatoputamen, and ocular tissues. Retinal degeneration was assessed using a scoring system where higher scores indicate less degeneration, with a score of 5 representing normal structure and 1 reflecting severe degeneration.

Results: In the MTX-M-MPZ-E group, the retinal degeneration score was higher than in MTX-M group (p = 0.002). The apoptosis index in the retina was highest in MTX-M group, while it was lower in MTX-M-MPZ-E group compared to MTX-M group (p = 0.018). In addition, the apoptosis index in the caudatoputamen was lower in MTX-M-MPZ-E group compared to MTX-M group (p = 0.009).

Conclusion: Combined elamipretide and methylprednisolone treatment improved optic nerve and retinal degeneration, reduced neuronal degeneration in the caudatoputamen, decreased oxidative stress and lipid peroxidation, and reduced apoptosis in the retina and caudatoputamen.

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乙胺嘧啶和甲基强的松龙治疗对甲醇中毒模型视神经、视网膜和脑损伤的影响:生化和组织病理学评估。
目的:本研究旨在从生化和组织病理学角度评估艾拉米雷特和甲基强的松龙对甲醇中毒所致脑、视神经和视网膜毒性的保护和治疗作用:本研究将 40 只雄性 Wistar Albino 大鼠分为 6 组:健康对照组(HC)、甲氨蝶呤组(MTX,0.3 mg/kg/d,7 d)、甲氨蝶呤+甲醇组(MTX-M,0.3 mg/kg/d, 7 d + 第 8 天甲醇 3 g/kg), 甲氨蝶呤 + 甲醇 + 甲基强的松龙(MTX-M-MPZ, 0.3 mg/kg/d, 7 d + 第 8 天甲醇 3 g/kg + MPZ 1 mg/kg/d, 3 d), 甲氨蝶呤 + 甲醇 + 艾拉米格雷(MTX-M-E, 0.3毫克/千克/天,持续7天+第8天甲醇3克/千克+艾拉米布雷特5毫克/千克/天,持续3天),以及甲氨蝶呤+甲醇+甲基强的松龙+艾拉米布雷特(MTX-M-MPZ-E,0.3毫克/千克/天,持续7天+第8天甲醇3克/千克+MPZ 1毫克/千克/天+艾拉米布雷特5毫克/千克/天,持续3天)。大鼠在最后一次给药后 8 小时安乐死。对血清、尾状核和眼组织进行组织病理学和生物化学评估。视网膜变性采用评分法进行评估,分数越高,变性程度越轻,5 分代表结构正常,1 分代表变性严重:结果:MTX-M-MPZ-E 组视网膜变性评分高于 MTX-M 组(P = 0.002)。MTX-M组视网膜凋亡指数最高,而MTX-M-MPZ-E组低于MTX-M组(p = 0.018)。此外,与 MTX-M 组相比,MTX-M-MPZ-E 组尾状突触的凋亡指数较低(p = 0.009):埃拉米雷特和甲基强的松龙联合治疗可改善视神经和视网膜变性,减少尾状突起神经元变性,降低氧化应激和脂质过氧化,减少视网膜和尾状突起的细胞凋亡。
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来源期刊
CiteScore
3.30
自引率
6.20%
发文量
40
审稿时长
1 months
期刊介绍: Cutaneous and Ocular Toxicology is an international, peer-reviewed journal that covers all types of harm to cutaneous and ocular systems. Areas of particular interest include pharmaceutical and medical products; consumer, personal care, and household products; and issues in environmental and occupational exposures. In addition to original research papers, reviews and short communications are invited, as well as concise, relevant, and critical reviews of topics of contemporary significance.
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