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Alpha-Lipoic Acid Ameliorates Radiation-Induced Salivary Gland Injury by Preserving Parasympathetic Innervation in Rats.

ABSTRACT: Radiation therapy is a standard treatment for patients with head and neck cancer. However, radiation exposure to the head and neck induces salivary gland (SG) dysfunction. Alpha lipoic acid (ALA) has been reported to reduce radiation-induced toxicity in normal tissues. In this study, we investigated the effect of ALA on radiation-induced SG dysfunction. Male Sprague-Dawley rats were assigned to the following treatment groups: control, ALA only (100 mg/kg, intraperitoneally), irradiation only, and ALA administration 24 h or 30 min prior to irradiation. The neck area, including SGs, was irradiated evenly at 2 Gy/min (total dose, 18 Gy) using a photon 6 MV linear accelerator. The rats were sacrificed at 2, 6, 8, and 12 weeks after irradiation. Radiation decreased SG weight, saliva secretion, AQP5 expression, parasympathetic innervation (GFR?2 and AchE expression), regeneration potentials (Shh and Ptch expression), salivary trophic factor levels (brain-derived neurotrophic factor and neurturin), and stem cell expression (Sca-1). These features were restored by treatment with ALA. This study demonstrated that ALA can rescue radiation-induced hyposalivation by preserving parasympathetic innervation and regenerative potentials.

SUBMITTER: Kim JH

PROVIDER: S-EPMC7178006 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Alpha-Lipoic Acid Ameliorates Radiation-Induced Salivary Gland Injury by Preserving Parasympathetic Innervation in Rats.

Kim Jin Hyun JH Jeong Bae Kwon BK Jang Si Jung SJ Yun Jeong Won JW Jung Myeong Hee MH Kang Ki Mun KM Kim Tae Gyu TG Woo Seung Hoon SH

International journal of molecular sciences 20200325 7

Radiation therapy is a standard treatment for patients with head and neck cancer. However, radiation exposure to the head and neck induces salivary gland (SG) dysfunction. Alpha lipoic acid (ALA) has been reported to reduce radiation-induced toxicity in normal tissues. In this study, we investigated the effect of ALA on radiation-induced SG dysfunction. Male Sprague-Dawley rats were assigned to the following treatment groups: control, ALA only (100 mg/kg, intraperitoneally), irradiation only, an ...[more]

PMID: 32218158

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Project description:It has been shown that removal of parasympathetic innervation to the lacrimal gland (LG) leads to rapid reduction in tear flow. Additionally, removal of the neural input resulted in disorganization of LG structure and changes in the expression of genes associated with the secretory pathway and inflammation. The goal of this study was to investigate the change in pro-inflammatory and pro-apoptotic gene expression in the rat LG following parasympathetic denervation. Male Long-Evans rats underwent unilateral sectioning of the greater superficial petrosal nerve and were sacrificed 7 days or 2.5 months later. cDNA was synthesized from LG RNA from the contralateral control (Ctla) and parasympathectomized (Px) glands and comparative real-time PCR was performed. Mean threshold cycles (MC(T)) for the Ctla and Px LG genes were normalized to 18S rRNA MC(T) values, and the relative fold change was calculated for each gene using the 2(-DeltaDeltaC)(T) method. The expression of nuclear factor kappa B1, caspase 1, eotaxin, leukocyte antigen MRC-OX44, allograft inflammatory factor-1, MHC class II molecules RT.1B and RT.1D, IgG receptor FcRn, and macrophage metalloelastase was increased and remained elevated in the Px LG, compared with the Ctla LG. Increased expression of the initiator of apoptosis gene, caspase 2, was confirmed, but expression of the executor gene, caspase 6, was not elevated in the Px LG. Reduced expression of genes associated with post-translational protein processing-furin convertase, protein disulfide isomerase, and UDP-gal transporter isozyme 1-was noted in the Px LG. No significant changes in the expression of genes associated with lysosomal and non-lysosomal-mediated protein degradation were found. Removal of parasympathetic input may lead to decreased capacity for protein synthesis and elevated immune responses in the Px LG. These changes occur without increases in expression of the muscarinic acetylcholine receptor subtype 3, and may suggest the early changes in LG acinar cells and the pathophysiology of autoimmune responses.

Dataset Information

Alpha-Lipoic Acid Ameliorates Radiation-Induced Salivary Gland Injury by Preserving Parasympathetic Innervation in Rats.

Publications

Alpha-Lipoic Acid Ameliorates Radiation-Induced Salivary Gland Injury by Preserving Parasympathetic Innervation in Rats.

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