Salidroside Ameliorates Radiation Damage by Reducing Mitochondrial Oxidative Stress in the Submandibular Gland

Abstract

Radiotherapy for patients with head and neck cancer inevitably causes radiation damage to salivary glands (SGs). Overproduction of reactive oxygen species (ROS) leads to mitochondrial damage and is critical in the pathophysiology of SG radiation damage. However, mitochondrial-targeted treatment is unavailable. Herein, both in vitro and in vivo models of radiation-damaged rat submandibular glands (SMGs) were used to investigate the potential role of salidroside in protecting irradiated SGs. Cell morphology was observed with an inverted phase-contrast microscope. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), mitochondrial ROS, mitochondrial membrane potential (MMP), and ATP were measured using relevant kits. The mitochondrial ultrastructure was observed under transmission electron microscopy. Cell apoptosis was determined by Western blot and TUNEL assays. Saliva was measured from Wharton’s duct. We found that salidroside protected SMG cells and tissues against radiation and improved the secretion function. Moreover, salidroside enhanced the antioxidant defense by decreasing MDA, increasing SOD, CAT, and GSH, and scavenging mitochondrial ROS. Furthermore, salidroside rescued the mitochondrial ultrastructure, preserved MMP and ATP, suppressed cytosolic cytochrome c and cleaved caspase 3 expression, and inhibited cell apoptosis. Together, these findings first identify salidroside as a mitochondrial-targeted antioxidant for preventing SG radiation damage.

Functional Polyphenol-Based Nanoparticles Boosted the Neuroprotective Effect of Riluzole for Acute Spinal Cord Injury

“…Furthermore, intracellular antioxidative mechanisms were also detected to assess the protective effects (riluzole, EGCG, and Ri@EGCG-2 NPs, 40 μg/mL). 48 Consistent with Collectively, these results demonstrated the great intracellular protective effects against oxidative stress.…”

“…In addition, a 2′,7′-dichlorofluorescein diacetate (DCFH-DA) fluorescent probe was utilized to detect ROS levels of HT 22 cells treated by H 2 O 2 (400 μM), and the results showed that both Ri@EGCG-2 NPs and EGCG significantly decreased the ROS levels compared with only the H 2 O 2 stimulation group (PC) and riluzole group (Figure E,F). Furthermore, intracellular antioxidative mechanisms were also detected to assess the protective effects (riluzole, EGCG, and Ri@EGCG-2 NPs, 40 μg/mL) . Consistent with the results of DCFH-DA assays, Ri@EGCG-2 NPs and EGCG significantly upregulated the levels of glutathione (GSH)/glutathione disulfide (GSSG) and superoxide dismutase (SOD) and downregulated the levels of malondialdehyde (MDA) compared with PC and riluzole groups (Figure G–I).…”

Advances in Antioxidant Applications for Combating 131I Side Effects in Thyroid Cancer Treatment

“…At the same time, the re-functionalization of red blood cell-based nanomaterials to enhance the targeted drug delivery strategy at the site of oxidative stress injury can also be considered as a key reference [ 125 ]. In addition, salidroside has been identified as a mitochondria-targeted antioxidant to prevent salivary gland damage caused by X-ray radiation [ 126 ]. The development of drugs that target 131 I-damaged organs and tissues may provide an alternative solution to the side effects associated with high doses of traditional antioxidants.…”