Effect of ischemic preconditioning on radiation damage to the submandibular gland in rats

Abstract

To investigate the effects of radiation on rat submandibular glands and the possible protective effects of ischemic preconditioning, the submandibular glands of Wistar rats were subjected to in situ radiation after ischemic preconditioning. The glands were exposed to X-radiation at a single dose of 20 Gy. Ischemic preconditioning was achieved by three min of ischemia and three min of reperfusion, repeated three times before irradiation. Salivary secretion, histological changes, alterations in tight junctions, and the levels of oxidative stress, pro-inflammatory cytokines, and water secretion proteins mediated by the muscarinic acetylcholine M3 subtype receptor were determined at 1 and 12 weeks post-irradiation. In glands subjected to irradiation only, the secretion, superoxide dismutase activity, tight junction width, acinar cell number, and M3 receptor and aquaporin-5 levels were lower at 1 and 12 weeks than seen in the ischemically preconditioned irradiated glands. In contrast, tumor necrosis factor-α, malondialdehyde, myeloperoxidase activity, and the expression of the tight junction protein claudin-4 were significantly higher in the irradiated only glands. Our study revealed that radiation caused a series of injury-stress responses, especially damage to the water secretion pathway mediated by the M3 receptor that ultimately led to hyposecretion, which might play an important role in the dysfunction of the irradiated only glands. Ischemic preconditioning reduced the radiation-induced injury to submandibular glands and ameliorated salivary hyposecretion.

Effect of Infliximab on Radiation-Induced Submandibular Gland Dysfunction in Rats

“…The irradiation and IFX groups (IRD + IFX) were exposed to radiation with IFX and sacrificed at 1, 6, and 12 weeks postirradiation. After an intraperitoneal injection of 10% chloral hydrate (350 mg/kg), the right SMG was irradiated with a single dose of 20 Gy ( 22 , 23 ). The portal was about 2.0 cm × 1.5 cm, and the rest was covered using a 3-mm thick-lead shield.…”

Insights into the Function of Aquaporins in Gastrointestinal Fluid Absorption and Secretion in Health and Disease

“…Reduced or loss of AQP5 expression [84,85] and/or altered AQP5 translocation [86] may participate to xerostomia in patients with head and neck cancer treated with ionizing radiation therapy. In addition, decreased AQP5 expression and saliva secretion were also detected following irradiation of the neck area in mice and rats [87][88][89][90][91] and could be reverted in rats by administration of pilocarpine, a muscarinic receptor agonist [92].…”

The role and mechanism of tight junctions in the regulation of salivary gland secretion

“…In addition to pilocarpine treatment, potential protective effect of ischemic preconditioning against radiation‐induced hyposalivation is also explored. In a rat radiation model, ischemic preconditioning (3 min of ischemia and 3 min of reperfusion, repeated three times before irradiation) reduces radiation‐induced injury, decreases claudin‐4 level, and ameliorates hyposecretion (Wu et al, 2021). These studies indicate that epithelial TJs are targets of radiation.…”