Melatonin and Metformin Mitigate Doxorubicin-Induced Alveolar Bone Toxicity.

Journal of dental research Pub Date : 2024-08-01 Epub Date: 2024-08-05 DOI:10.1177/00220345241261980
B Srivichit, C Thonusin, R Aeimlapa, A Arinno, T Chunchai, N Charoenphandhu, N Chattipakorn, S C Chattipakorn
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Abstract

Evidence concerning the osteotoxic effects of chemotherapy (doxorubicin) has been previously described. Periodontitis also progressively increases in patients receiving chemotherapy; however, the beneficial effects of melatonin and metformin on the alleviation of doxorubicin-induced osteotoxicity have never been investigated. Therefore, we investigated the negative impact of doxorubicin on alveolar bone homeostasis and the benefits of melatonin and metformin on the attenuation of doxorubicin-induced alveolar bone toxicity. Male Wistar rats were divided into 4 groups to receive either 1 mL of normal saline solution as a control group, 3 mg/kg of doxorubicin, 3 mg/kg of doxorubicin plus 10 mg/kg of melatonin, or 3 mg/kg of doxorubicin plus 250 mg/kg of metformin. Doxorubicin treatment was given on days 0, 4, 8, 15, 22, and 29, while interventions were given daily on days 0 to 29. Following euthanasia, blood and alveolar bones were collected for evaluation of oxidative stress, bone remodeling, inflammation, microarchitecture, and periodontal condition. We found that doxorubicin increased systemic oxidative stress, decreased antioxidative capacity, increased inflammation, decreased bone formation, increased bone reabsorption, impaired microarchitecture, and impaired periodontal condition of the alveolar bone. Although cotreatment with melatonin or metformin resulted in some improvement in these parameters, cotreatment with melatonin was more effective than cotreatment with metformin in terms of decreasing oxidative stress, reducing bone resorption, and improving microarchitecture and periodontal condition. All of these findings highlight the potential for antioxidants, especially melatonin, to ameliorate doxorubicin-induced alveolar bone toxicity.

褪黑素和二甲双胍可减轻多柔比星诱发的肺泡骨毒性
化疗(多柔比星)对骨毒性的影响已有相关证据。然而,褪黑素和二甲双胍对缓解多柔比星引起的骨毒性的有益作用却从未被研究过。因此,我们研究了多柔比星对牙槽骨稳态的负面影响,以及褪黑素和二甲双胍对减轻多柔比星诱导的牙槽骨毒性的益处。雄性 Wistar 大鼠被分为 4 组,分别接受 1 mL 生理盐水作为对照组、3 mg/kg 多柔比星、3 mg/kg 多柔比星加 10 mg/kg 褪黑激素或 3 mg/kg 多柔比星加 250 mg/kg 二甲双胍。多柔比星治疗在第0、4、8、15、22和29天进行,而干预则在第0至29天每天进行。安乐死后,收集血液和牙槽骨以评估氧化应激、骨重塑、炎症、微结构和牙周状况。我们发现,多柔比星增加了全身氧化应激,降低了抗氧化能力,增加了炎症,减少了骨形成,增加了骨再吸收,损害了微结构,损害了牙槽骨的牙周状况。虽然褪黑素或二甲双胍联合治疗可在一定程度上改善这些参数,但在降低氧化应激、减少骨吸收、改善微结构和牙周状况方面,褪黑素联合治疗比二甲双胍联合治疗更有效。所有这些发现都凸显了抗氧化剂,尤其是褪黑素在改善多柔比星诱导的牙槽骨毒性方面的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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