The parotid glands are damaged by oxidative stress and a series of pathophysiological changes after irradiation. Rosmarinic acid (RA) is a natural antioxidant that provides a radioprotective effect against harmful damage from ionizing radiation. The present study aims to explore the protective effects of RA on radiation-induced parotid gland injury and its underlying mechanism. Sprague-Dawley rats were irradiated with 15 Gy X-ray and treated with different concentrations of RA (30, 60, and 120 mg/kg) or amifostine (AMI, 250 mg/kg). Saliva secretion function, oxidative stress, apoptosis, the inflammatory response, and fibrosis were determined by the measurement of the salivary flow rate, enzyme-linked immunosorbent assay, transferase-mediated DUTP Nick end labeling, Western blot, quantitative real time polymerase chain reaction, and hematoxylin and eosin staining. Here, we show that RA treatment significantly attenuated reactive oxygen species by a direct hindrance effect and the indirect activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nicotinamide adenine dinucleotide phosphate oxidase 4 signaling. Rosmarinic acid not only reduced apoptosis by inhibiting p53/jun N-terminal kinase activation but also reduced parotid gland tissue fibrosis by downregulating inflammatory factor levels. Compared to AMI, RA has the obvious advantages of late efficacy and convenient usage. Moreover, 60 mg/kg is the minimum effective dose of RA. Therefore, RA can potentially be applied as a therapeutic radioprotective agent to treat radiation-induced parotid gland injury in the future.

中文翻译：

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迷迭香酸对放射线致腮腺损伤的保护作用及其作用机制。

腮腺受到氧化应激和放射后一系列病理生理变化的损害。迷迭香酸（RA）是一种天然抗氧化剂，可提供防辐射作用，防止电离辐射造成有害损害。本研究旨在探讨类风湿关节炎对辐射引起的腮腺损伤的保护作用及其潜在机制。用15 Gy X射线照射Sprague-Dawley大鼠，并用不同浓度的RA（30、60和120 mg / kg）或氨磷汀（AMI，250 mg / kg）处理。通过测量唾液流速，酶联免疫吸附测定，转移酶介导的DUTP Nick末端标记，Western印迹，定量实时聚合酶链反应确定唾液分泌功能，氧化应激，细胞凋亡，炎症反应和纤维化 以及苏木精和曙红染色。在这里，我们显示RA治疗通过直接的阻碍作用和过氧化物酶体增殖物激活受体γ辅激活物1-α/烟酰胺腺嘌呤二核苷酸磷酸氧化酶4信号的间接激活显着减弱了活性氧。迷迭香酸不仅通过抑制p53 / jun N末端激酶的活化来减少细胞凋亡，还可以通过下调炎症因子的水平来减少腮腺组织纤维化。与AMI相比，RA具有后期疗效好，使用方便的明显优点。此外，60 mg / kg是RA的最低有效剂量。因此，RA将来有可能被用作治疗性放射防护剂，以治疗辐射诱发的腮腺损伤。我们显示，RA治疗通过直接阻碍作用和过氧化物酶体增殖物激活受体γ辅激活物1-α/烟酰胺腺嘌呤二核苷酸磷酸氧化酶4信号的间接激活显着减弱了活性氧。迷迭香酸不仅通过抑制p53 / jun N末端激酶的活化来减少细胞凋亡，还可以通过下调炎症因子的水平来减少腮腺组织纤维化。与AMI相比，RA具有后期疗效好，使用方便的明显优点。此外，60 mg / kg是RA的最低有效剂量。因此，RA将来有可能被用作治疗性放射防护剂，以治疗辐射诱发的腮腺损伤。我们显示，RA治疗通过直接阻碍作用和过氧化物酶体增殖物激活受体γ辅激活物1-α/烟酰胺腺嘌呤二核苷酸磷酸氧化酶4信号的间接激活显着减弱了活性氧。迷迭香酸不仅通过抑制p53 / jun N末端激酶的活化来减少细胞凋亡，还可以通过下调炎症因子的水平来减少腮腺组织纤维化。与AMI相比，RA具有后期疗效好，使用方便的明显优点。此外，60 mg / kg是RA的最低有效剂量。因此，RA将来有可能被用作治疗性放射防护剂，以治疗辐射诱发的腮腺损伤。