Radioprotective effects of pyrroloquinoline quinone on parotid glands in C57BL/6J mice

Huang,Yuanqing; Chen,Ning; Miao,Dengshun

doi:10.3892/etm.2016.3843

Radioprotective effects of pyrroloquinoline quinone on parotid glands in C57BL/6J mice

Authors:
- Yuanqing Huang
- Ning Chen
- Dengshun Miao
View Affiliations

Affiliations: Department of Stomatology, Hunan University of Medicine, Huaihua, Hunan 418000, P.R. China, Institute of Stomatology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, State Key Laboratory of Reproductive Medicine, The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: October 26, 2016 https://doi.org/10.3892/etm.2016.3843
Pages: 3685-3693
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to investigate whether pyrroloquinoline quinine (PQQ) serve a radioprotective role in parotid gland damage induced by total body irradiation (TBI) in C57BL/6J mice. A total of 15 female 8‑week‑old C57BL/6J mice were randomly assigned into three treatment groups: i) Untreated control (no irradiation); ii) 4 gray (Gy) X-ray irradiation; iii) 4 Gy X‑ray irradiation with additional dietary PQQ (4 mg PQQ/kg in normal diet). Each group included five mice. After 4 weeks, all animals were collected for evaluating the phenotype, body weight, pathological and biochemical parameters. The results indicated that PQQ had biological effects on total body phenotype. PQQ could partially rescue TBI‑induced damage to parotid glands. In addition, PQQ served radioprotective effects on parotid glands via multiple mechanisms, such as promoting proliferation, inhibiting apoptosis and senescence, upregulating antioxidant ability, scavenging reactive oxygen species and reducing DNA damage. The results of the present study demonstrate that PQQ serves a radioprotective role in parotid gland damage induced by TBI, possibly via inhibiting oxidative stress and participating in DNA damage repair. The study provides experimental and theoretical knowledge for the development of radioprotective clinical drugs.

View Figures

View References

1	Mizoe JE, Hasegawa A, Jingu K, Takagi R, Bessyo H, Morikawa T, Tonoki M, Tsuji H, Kamada T, Tsujii H and Okamoto Y: Organizing Committee for the Working Group for Head Neck Cancer: Results of carbon ion radiotherapy for head and neck cancer. Radiother Oncol. 103:32–37. 2012. View Article : Google Scholar : PubMed/NCBI
2	Hamlet S, Faull J, Klein B, Aref A, Fontanesi J, Stachler R, Shamsa F, Jones L and Simpson M: Mastication and swallowing in patients with postirradiation xerostomia. Int J Radiat Oncol Biol Phys. 37:789–796. 1997. View Article : Google Scholar : PubMed/NCBI
3	Logemann JA, Pauloski BR, Rademaker AW, Lazarus CL, Mittal B, Gaziano J, Stachowiak L, MacCracken E and Newman LA: Xerostomia: 12-month changes in saliva production and its relationship to perception and performance of swallow function, oral intake, and diet after chemoradiation. Head Neck. 25:432–437. 2003. View Article : Google Scholar : PubMed/NCBI
4	Nunez MI, McMillan TJ, Valenzuela MT, de Almodóvar JM Ruiz and Pedraza V: Relationship between DNA damage, rejoining and cell killing by radiation in mammalian cells. Radiother Oncol. 39:155–165. 1996. View Article : Google Scholar : PubMed/NCBI
5	Di Pietro C, Piro S, Tabbi G, Ragusa M, Di Pietro V, Zimmitti V, Cuda F, Anello M, Consoli U, Salinaro ET, et al: Cellular and molecular effects of protons: Apoptosis induction and potential implications for cancer therapy. Apoptosis. 11:57–66. 2006. View Article : Google Scholar : PubMed/NCBI
6	Wang Y, Liu L, Pazhanisamy SK, Li H, Meng A and Zhou D: Total body irradiation causes residual bone marrow injury by induction of persistent oxidative stress in murine hematopoietic stem cells. Free Radic Biol Med. 48:348–356. 2010. View Article : Google Scholar : PubMed/NCBI
7	Hauge JG: Glucose dehydrogenase of bacterium anitratum: An enzyme with a novel prosthetic group. J Biol Chem. 239:3630–3639. 1964.PubMed/NCBI
8	Duine JA: Cofactor diversity in biological oxidations: Implications and applications. Chem Rec. 1:74–83. 2001. View Article : Google Scholar : PubMed/NCBI
9	Mitchell AE, Jones AD, Mercer RS and Rucker RB: Characterization of pyrroloquinoline quinone amino acid derivatives by electrospray ionization mass spectrometry and detection in human milk. Anal Biochem. 269:317–325. 1999. View Article : Google Scholar : PubMed/NCBI
10	Kumazawa T, Sato K, Seno H, Ishii A and Suzuki O: Levels of pyrroloquinoline quinone in various foods. Biochem J. 307:331–333. 1995. View Article : Google Scholar : PubMed/NCBI
11	Stites TE, Mitchell AE and Rucker RB: Physiological importance of quinoenzymes and the O-quinone family of cofactors. J Nutr. 130:719–727. 2000.PubMed/NCBI
12	Steinberg FM, Gershwin ME and Rucker RB: Dietary pyrroloquinoline quinone: Grono irradiationh and immune response in BALB/c mice. J Nutr. 124:744–753. 1994.PubMed/NCBI
13	Steinberg F, Stites TE, Anderson P, Storms D, Chan I, Eghbali S and Rucker R: Pyrroloquinoline quinone improves grono irradiationh and reproductive performance in mice fed chemically defined diets. Exp Biol Med (Maywood). 228:160–166. 2003.PubMed/NCBI
14	Zhang Y, Feustel PJ and Kimelberg HK: Neuroprotection by pyrroloquinoline quinone (PQQ) in reversible middle cerebral artery occlusion in the adult rat. Brain Res. 1094:200–206. 2006. View Article : Google Scholar : PubMed/NCBI
15	Zhang Y and Rosenberg PA: The essential nutrient pyrroloquinoline quinone may act as a neuroprotectant by suppressing peroxynitrite formation. Eur J Neurosci. 16:1015–1024. 2002. View Article : Google Scholar : PubMed/NCBI
16	Zhu BQ, Simonis U, Cecchini G, Zhou HZ, Li L, Teerlink JR and Karliner JS: Comparison of pyrroloquinoline quinone and/or metoprolol on myocardial infarct size and mitochondrial damage in a rat model of ischemia/reperfusion injury. J Cardiovasc Pharmacol Ther. 11:119–128. 2006. View Article : Google Scholar : PubMed/NCBI
17	Ohwada K, Takeda H, Yamazaki M, Isogai H, Nakano M, Shimomura M, Fukui K and Urano S: Pyrroloquinoline Quinone (PQQ) prevents cognitive deficit caused by oxidative stress in rats. J Clin Biochem Nutr. 42:29–34. 2008. View Article : Google Scholar : PubMed/NCBI
18	Shankar BS, Pandey R, Amin P, Misra HS and Sainis KB: Role of glutathione in augmenting the anticancer activity of pyrroloquinoline quinone (PQQ). Redox Rep. 15:146–154. 2010. View Article : Google Scholar : PubMed/NCBI
19	Ouchi A, Nakano M, Nagaoka S and Mukai K: Kinetic study of the antioxidant activity of pyrroloquinolinequinol (PQQH(2), a reduced form of pyrroloquinolinequinone) in micellar solution. J Agric Food Chem. 57:450–456. 2009. View Article : Google Scholar : PubMed/NCBI
20	Stites T, Storms D, Bauerly K, Mah J, Harris C, Fascetti A, Rogers Q, Tchaparian E, Satre M and Rucker RB: Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice. J Nutr. 136:390–396. 2006.PubMed/NCBI
21	Ishii T, Akagawa M, Naito Y, Handa O, Takagi T, Mori T, Kumazawa S, Yoshikawa T and Nakayama T: Pro-oxidant action of pyrroloquinoline quinone: Characterization of protein oxidative modifications. Biosci Biotechnol Biochem. 74:663–666. 2010. View Article : Google Scholar : PubMed/NCBI
22	Tao R, Karliner JS, Simonis U, Zheng J, Zhang J, Honbo N and Alano CC: Pyrroloquinoline quinone preserves mitochondrial function and prevents oxidative injury in adult rat cardiac myocytes. Biochem Biophys Res Commun. 363:257–262. 2007. View Article : Google Scholar : PubMed/NCBI
23	Misra HS, Khairnar NP, Barik A, Priyadarsini K Indira, Mohan H and Apte SK: Pyrroloquinoline-quinone: A reactive oxygen species scavenger in bacteria. FEBS Lett. 578:26–30. 2004. View Article : Google Scholar : PubMed/NCBI
24	Bauerly K, Harris C, Chowanadisai W, Graham J, Havel PJ, Tchaparian E, Satre M, Karliner JS and Rucker RB: Altering pyrroloquinoline quinone nutritional status modulates mitochondrial, lipid, and energy metabolism in rats. PLoS One. 6:e217792011. View Article : Google Scholar : PubMed/NCBI
25	Liu H, Guo J, Wang L, Chen N, Karaplis A, Goltzman D and Miao D: Distinctive anabolic roles of 1,25-dihydroxyvitamin D(3) and parathyroid hormone in teeth and mandible versus long bones. J Endocrinol. 203:203–213. 2009. View Article : Google Scholar : PubMed/NCBI
26	Kressel M and Groscurth P: Distinction of apoptotic and necrotic cell death by in situ labelling of fragmented DNA. Cell Tissue Res. 278:549–556. 1994. View Article : Google Scholar : PubMed/NCBI
27	Xue Y, Karaplis AC, Hendy GN, Goltzman D and Miao D: Genetic models show that parathyroid hormone and 1,25-dihydroxyvitamin D3 play distinct and synergistic roles in postnatal mineral ion homeostasis and skeletal development. Hum Mol Genet. 14:1515–1528. 2005. View Article : Google Scholar : PubMed/NCBI
28	Zamzami N, Marchetti P, Castedo M, Decaudin D, Macho A, Hirsch T, Susin SA, Petit PX, Mignotte B and Kroemer G: Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death. J Exp Med. 182:367–377. 1995. View Article : Google Scholar : PubMed/NCBI
29	Franke RM, Herdly J and Phillipe E: Acquired dental defects and salivary gland lesions after irradiation for carcinoma. J Am Dent Assoc. 70:868–883. 1965. View Article : Google Scholar : PubMed/NCBI
30	Cherry CP and Gluckman A: Injury and repair following irradiation of salivary glands in male rats. Br J Radiol. 32:596–608. 1959. View Article : Google Scholar : PubMed/NCBI
31	Phillipe RM: X-ray-induced changes in function and structure of the rat parotid gland. J Oral Surg. 28:432–437. 1970.PubMed/NCBI
32	Sholley MM, Sodicoff M and Pratt NE: Early radiation injury in the rat parotid gland. Reaction of acinar cells and vascular endothelium. Lab Invest. 31:340–354. 1974.PubMed/NCBI
33	Dirix P, Nuyts S and Van den Bogaert W: Radiation-induced xerostomia in patients with head and neck cancer: A literature review. Cancer. 107:2525–2534. 2006. View Article : Google Scholar : PubMed/NCBI
34	Nuñez MI, McMillan TJ, Valenzuela MT, de Almodóvar JM Ruiz and Pedraza V: Relationship between DNA damage, rejoining and cell killing by radiation in mammalian cells. Radiother Oncol. 39:155–165. 1996. View Article : Google Scholar : PubMed/NCBI
35	Umegaki K, Aoki S and Esashi T: Whole body X-ray irradiation to mice decreases ascorbic acid concentration in bone marrow: Comparison between ascorbic acid and vitamin E. Free Radic Biol Med. 19:493–497. 1995. View Article : Google Scholar : PubMed/NCBI
36	Umegaki K and Ichikawa T: Decrease in vitamin E levels in the bone marrow of mice receiving whole-body X-ray irradiation. Free Radic Biol Med. 17:439–444. 1994. View Article : Google Scholar : PubMed/NCBI
37	Liem IH, Olmos RA, Balm AJ, Keus RB, van Tinteren H, Takes RP, Muller SH, Bruce AM, Hoefnagel CA and Hilgers FJ: Evidence for early and persistent impairment of salivary gland excretion after irradiation of head and neck tumours. Eur J Nucl Med. 23:1485–1490. 1996. View Article : Google Scholar : PubMed/NCBI
38	Taylor SE and Miller EG: Preemptive pharmacologic intervention in radiation-induced salivary dysfunction. Proc Soc Exp Biol Med. 221:14–26. 1999. View Article : Google Scholar : PubMed/NCBI
39	Nagler RM: The enigmatic mechanism of irradiation-induced damage to the major salivary glands. Oral Dis. 8:141–146. 2002. View Article : Google Scholar : PubMed/NCBI
40	Nagler RM, Baum BJ and Fox PC: Acute effects of X irradiation on the function of rat salivary glands. Radiat Res. 136:42–47. 1993. View Article : Google Scholar : PubMed/NCBI
41	Pontual ML, Tuji FM, Barros SP, Bóscolo FN, Novaes PD and de Almeida SM: Ultrastructural evaluation of the radioprotective effect of sodium selenite on submandibular glands in rats. J Appl Oral Sci. 15:162–168. 2007. View Article : Google Scholar : PubMed/NCBI
42	Medina VA, Prestifilippo JP, Croci M, Carabajal E, Bergoc RM, Elverdin JC and Rivera ES: Histamine prevents functional and morphological alterations of submandibular glands induced by ionising radiation. Int J Radiat Biol. 87:284–292. 2011. View Article : Google Scholar : PubMed/NCBI
43	Cotrim AP, Hyodo F, Matsumoto K, Sowers AL, Cook JA, Baum BJ, Krishna MC and Mitchell JB: Differential radiation protection of salivary glands versus tumor by Tempol with accompanying tissue assessment of Tempol by magnetic resonance imaging. Clin Cancer Res. 13:4928–4933. 2007. View Article : Google Scholar : PubMed/NCBI