DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20171236

The effects of astaxanthin on salivary gland damage caused by cisplatin in the rat

Suat Terzi, Abdulkadir Özgür, Tolga Mercantepe, Metin Çeliker, Levent Tümkaya, Engin Dursun

Abstract


Background: Cisplatin is a potent antineoplastic agent widely used for a variety of malignancies. However, it has many dose-limiting side effects such as neurotoxicity, cytotoxicity and ototoxicity. The aim of our study was to determine the effectiveness of astaxanthin (ASX) as a cytoprotective agent against cisplatin-induced cytotoxicity in the submandibular glands of rats.

Methods: Thirty-six adult male Wistar albino rats were divided into six groups as follows: group I: saline control; group II: 75 mg/kg/day ASX; group III: 16 mg/kg cisplatin; group IV: 25 mg/kg/day ASX + cisplatin; group V: 75 mg/kg/day ASX + cisplatin; group VI: olive oil + cisplatin. In all groups, submandibular gland histopathological and histochemical investigations were done using a light microscope. Every rat section was semi-quantitatively scored. Neutrophil infiltration density, myoepithelial cell density in the degeneration area, degenerative granular duct cell density, degenerative seromucous acinus cell density, and changes in the content of the secretory granules of seromucous acini and granular ducts of the parenchyma and stroma were calculated.

Results: The results of the analysis of the mean acinus area of the submandibular gland revealed that there was a significant decrease in cisplatin group rats when compared to control rats (p<0.05, p=0.00). However, there was no significant difference between-group IV, V and control group in terms of mean acinus area. (p=0.541, p=0.773). The results of the analysis of the mean ducts area of the submandibular gland also showed that there were significant increased group III compared to control rats (p<0.05, p=0.031). There was no significant difference between-group IV, V and control group in terms of mean ducts area (p>0.05, p=0.921). Similarities were observed in the mean ducts area with the group IV and the group V (p>0.05, p=0.571).

Conclusions: These results suggest the possibility that the clinical use of ASX could reduce or prevent damage to the salivary gland of patients receiving cisplatin chemotherapy.

Keywords


Astaxanthin, Cisplatin, Protective effect, Submandibular gland

Full Text:

PDF

References


Sonis ST. Oral mucositis in cancer therapy. J Support Oncol. 2004;2 (Suppl. 3):3-8.

Kitashima S. Morphological alterations of submandibular glands caused by cisplatin in the rat. Kurume med J. 2005;52:29-38.

Ozel O, Ayçiçek A, Kenar F, Aktepe F, Sargın R, Yılmaz M, et al. Histopathologic changes in the rabbit submandibular gland after 5-fluorouracil chemotherapy. Turk J Med Sci. 2010;40(2):213-20.

Mittal BB, Pauloski BR, Rademaker AW, Discekici-Harris M, Helenowski IB, Mellot A, et al. Effect of induction chemotherapy on swallow physiology and saliva production in patients with head and neck cancer: a pilot study. Head Neck. 2015;37(4):567-72.

Hamers FPT, Brakkee JH, Cavalletti E. Reduced glutathione protects against cisplatin-induced neurotoxicity in rats. Cancer Res. 1993;53:544-9.

Rybak LP, Ravi R, Somani SM. Mechanism of protection by diethyldithiocarbamate against cisplatin ototoxicity: antioxidant system. Fund Appl Toxicol. 1995;26:293-300.

Ravi R, Somani SM, Rybak LP. Mechanism of cisplatin ototoxicity: antioxidant system. Pharmacol Toxicol. 1995;76:386-94.

Ghlissi Z, Hakim A, Sila A, Mnif H, Zeghal K, Rebai T, Bougatef A, Sahnoun Z.Evaluation of efficacy of natural astaxanthin and vitamin E in prevention of colistin-induced nephrotoxicity in the rat model. Environ Toxicol Pharmacol. 2014;37(3):960-6.

Pashkow FJ, Watumull DG, Campbell CL. Astaxanthin: a novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Am J Cardiol. 2008;101(10A):58D-68D.

Chew BP, Park JS, Wong MW, Wong TS. A comparison of the anticancer activities of dietary beta-carotene, canthaxanthin and astaxanthin in mice in vivo. Anticancer Res. 1999;19:1849-53.

Ohgami K, Shiratori K, Kotake S, Nishida T, Mizuki N, Yazawa K, et al. Effects of astaxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo. Invest Ophthalmol Vis Sci. 2003;44:2694-701.

Uchiyama K, Naito Y, Hasegawa G, Nakamura N, Takahashi J, Yoshikawa T. Astaxanthin protects beta-cells against glucose toxicity in diabetic db/db mice. Redox Rep. 2002;7:290-3.

Kang JO, Kim SJ, Kim H. Effect of astaxanthin on the hepatotoxicity, lipid peroxidation and antioxidative enzymes in the liver of CCl4-treated rats. Methods Find Exp Clin Pharmacol. 2001;23:79-84.

Demiroz Abakay C, Şahintürk K, Türk A, Özkan L, Özmen A. Our results of postoperative radiation therapy in patients with salivary gland cancer. Kulak Burun Bogaz Ihtis Derg. 2014;24(6):316-23.

Hey J, Setz J, Gerlach R, Vordermark D, Gernhardt CR, Kuhnt T. Effect of Cisplatin on parotid gland function in concomitant radiochemotherapy. Int J Radiat Oncol Biol Phys. 2009;75(5):1475-80.

Yamamoto T, Staples J, Wataha J. Protective effects of EGCG on salivary gland cells treated with gamma-radiation or cis-platinum(II)diammine dichloride. Anticancer Res. 2004;24:3065-73.

Kosuda S, Satoh M, Yamamoto F, Uematsu M, Kusano S. As- sessment of salivary gland dysfunction following chemoradio- therapy using quantitative salivary gland scintigraphy. Int J Radiat Oncol Biol Phys. 1999;45:379-84.