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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. [ABSTRACT FROM AUTHOR]

Purpose: The impairment of the salivary glands is a permanent side effect of 131I ablation therapy for patients with differentiated thyroid cancer. Effective and safe treatments for protecting the salivary glands against 131I are currently not available. Mitochondria are susceptible to ionizing radiation, but alterations after 131I exposure are unknown. Here, we investigated the mechanisms of 131I damage in submandibular glands (SMGs) and evaluated the cytoprotective effect of phenylephrine (PE) against mitochondrial radiation damage.Methods and Materials: Rats were randomly divided into 4 groups: control, PE alone, 131I alone, and 131I with PE pretreatment. The mitochondrial structure of SMGs was observed under transmission electron microscopy. Apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Cytochrome c, cleaved-caspase 3, SIRT1, NAMPT, and PGC-1α protein levels were determined with Western blot and immunohistochemistry. Levels of mitochondrial membrane potential, nicotinamide adenine dinucleotide (NAD), and adenosine triphosphate (ATP) were measured with relevant kits.Results: After exposing rat SMGs to 131I, the mitochondrial membrane structures were destroyed, the mitochondrial membrane potential decreased, the release of cytochrome c increased, and cleaved-caspase 3 and cell apoptosis were activated. Moreover, the expression of SIRT1, NAMPT, and PGC-1α was downregulated, and the levels of NAD and ATP decreased. In contrast, PE alleviated the 131I-induced mitochondrial damages and upregulated the expression of SIRT1/NAMPT/PGC-1α and the levels of NAD and ATP.Conclusions: These findings demonstrate that 131I impairs the salivary glands via the downregulation of SIRT1/NAMPT/PGC-1α signal pathways, which disturbs mitochondrial homeostasis. PE alleviated the 131I damage in SMGs at the mitochondrial level, suggesting that PE could be used as a potential radioprotector for patients with differentiated thyroid cancer with radiation sialadenitis. [ABSTRACT FROM AUTHOR]

• Treatment with albiflorin protected the mitochondrial dynamics in APP/PS1 mice. • Treatment with albiflorin reduced β-Amyloid accumulation in APP/PS1 mice. • Treatment with albiflorin ameliorated memory deficits in APP/PS1 mice. Albiflorin, the main component of Radix Paeoniae Alba, has been shown to ameliorate injury in cell models of Alzheimer's disease induced by amyloid-β (Aβ), but the mechanism is unclear. We used 7-month-old APP/PS1 mice to determine whether albiflorin is capable of protecting against Alzheimer's disease. We found that four weeks of intragastric administration of albiflorin (20 mg/kg/d and 40 mg/kg/d) ameliorated memory deficits in APP/PS1 mice. Albiflorin conferred synaptic protection by decreasing Aβ levels and increasing PSD-95, synaptophysin and synapsin 1 levels in the brains of APP/PS1 mice. Albiflorin played an antioxidative role by reducing reactive oxygen species (ROS) levels and elevating Mn-SOD activity in the brain. Albiflorin also reduced the level of Drp1, increased the levels of Mfn1, Mfn2 and Opa1 and improved mitochondrial morphology in APP/PS1 mice. Albiflorin inhibited the mitochondrial pathway of apoptosis by increasing the levels of Bcl-2 and Bcl-xl and decreasing the levels of Bax, caspase-3 and cytochrome c in both the hippocampus and the cortex and by reducing the number of apoptotic cells in the anterior parietal cortex of the APP/PS1 mice. In conclusion, treatment with albiflorin improved mitochondrial function, reduced Aβ deposition in the brain and ameliorated memory deficits in APP/PS1 mice. These findings indicate that albiflorin may serve as a potential antidementia drug. [ABSTRACT FROM AUTHOR]