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己酮可可碱和α-生育酚对大鼠拔牙前后药物相关性颌骨坏死的影响。

Effect of pentoxifylline and α-tocopherol on medication-related osteonecrosis of the jaw in rats: Before and after dental extraction.

作者信息

Delfrate Gabrielle, Mroczek Tayline, Mecca Leomar Emanuel Almeida, Andreis Jéssica Daniela, Fernandes Daniel, Lipinski Leandro Cavalcante, Claudino Marcela, Franco Gilson Cesar Nobre

机构信息

Department of Dentistry, State University of Ponta Grossa (UEPG), General Carlos Cavalcanti, 4748 - Uvaranas, Ponta Grossa, PR 84030-900, Brazil.

Department of Pharmacology, Federal University of Santa Catarina (UFSC), University Campus, Block D - Trindade, Florianopolis, SC 88049-900, Brazil.

出版信息

Arch Oral Biol. 2022 May;137:105397. doi: 10.1016/j.archoralbio.2022.105397. Epub 2022 Mar 11.

Abstract

OBJECTIVE

Evaluate the effect of pentoxifylline and α-tocopherol administration in the prevention or treatment of medication-related jaw osteonecrosis (MRONJ).

METHODOLOGY

Sixty Wistar rats were divided into three prevention (C-prev, BP-prev and BP/PT-prev) and three treatment groups (C-treat, BP-treat and BP/PT-treat), n = 10. The animals in the BP-prev, BP/PT-prev, BP-treat and BP/PT-treat groups received zoledronic acid (0.1 mg/kg) for 12 weeks, while the animals in the C-prev and C-treat groups received saline solution. At week 6, all animals underwent tooth extraction. Between week 5 and week 12, the BP/PT-prev group was treated with pentoxifylline (50 mg/kg/day) and α-tocopherol (80 mg/kg/day), with euthanasia at the end of week 12. The BP/PT-treat group received the same drug protocol, but it was performed between week 12 and week 16, with euthanasia at the end of week 16. Afterwards, the presence of osteonecrosis was evaluated by clinical analysis, radiographic and histological.

RESULTS

BP/PT-treat group showed a reduction in the histological incidence of osteonecrosis by 50%, decrease the percentage of empty osteocyte gaps and the necrotic area, decrease the presence of bone sequestration and increase the number of osteocytes and alveolar blood flow (p < 0.05). However, BP/PT-prev group showed only a reduction in the necrotic area percentage when compared to BP-prev (p < 0.05).

CONCLUSIONS

Pentoxifylline and α-tocopherol administration before tooth extraction was not effective in preventing MRONJ. However, this drug protocol was able to reduce MRONJ manifestation when administrate after discontinuation of bisphosphonate, thus it can be considered as a viable strategy for the treatment of this pathological condition.

摘要

目的

评估己酮可可碱和α-生育酚给药在预防或治疗药物相关性颌骨坏死(MRONJ)中的作用。

方法

将60只Wistar大鼠分为三个预防组(C-prev、BP-prev和BP/PT-prev)和三个治疗组(C-treat、BP-treat和BP/PT-treat),每组n = 10。BP-prev、BP/PT-prev、BP-treat和BP/PT-treat组的动物接受唑来膦酸(0.1 mg/kg)治疗12周,而C-prev和C-treat组的动物接受生理盐水。在第6周时,所有动物均接受拔牙。在第5周和第12周之间,BP/PT-prev组用己酮可可碱(50 mg/kg/天)和α-生育酚(80 mg/kg/天)治疗,在第12周结束时实施安乐死。BP/PT-treat组接受相同的药物方案,但在第12周和第16周之间进行,在第16周结束时实施安乐死。之后,通过临床分析、影像学和组织学评估骨坏死的存在情况。

结果

BP/PT-treat组骨坏死的组织学发生率降低了50%,空骨细胞间隙百分比和坏死面积减少,骨分离现象减少,骨细胞数量和牙槽血流量增加(p < 0.05)。然而,与BP-prev组相比,BP/PT-prev组仅坏死面积百分比有所降低(p < 0.05)。

结论

拔牙前给予己酮可可碱和α-生育酚对预防MRONJ无效。然而,在停用双膦酸盐后给予该药物方案能够减轻MRONJ的表现,因此可被视为治疗这种病理状况的一种可行策略。

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