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.

中文翻译：

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褪黑激素和二甲双胍减轻阿霉素引起的牙槽骨毒性


有关化疗（阿霉素）骨毒性作用的证据先前已有描述。在接受化疗的患者中，牙周炎也会逐渐增加；然而，褪黑激素和二甲双胍对减轻阿霉素引起的骨毒性的有益作用从未被研究过。因此，我们研究了阿霉素对牙槽骨稳态的负面影响以及褪黑激素和二甲双胍对减弱阿霉素引起的牙槽骨毒性的益处。将雄性 Wistar 大鼠分为 4 组，分别接受 1 mL 生理盐水溶液作为对照组、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。在第 0、4、8、15、22 和 29 天进行阿霉素治疗，在第 0 至 29 天每天进行干预。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。我们发现阿霉素会增加全身氧化应激，降低抗氧化能力，增加炎症，减少骨形成，增加骨重吸收，损害牙槽骨的微结构和牙周状况。尽管与褪黑激素或二甲双胍联合治疗导致这些参数有所改善，但在减少氧化应激、减少骨吸收、改善微结构和牙周状况方面，与二甲双胍联合治疗相比，与褪黑激素联合治疗更有效。所有这些发现都强调了抗氧化剂（尤其是褪黑激素）改善阿霉素引起的牙槽骨毒性的潜力。