Effect of hesperetin derivatives on the development of selenite‑induced cataracts in rats

Nakazawa,Yosuke; Pauze,Martin; Fukuyama,Kazuya; Nagai,Noriaki; Funakoshi‑Tago,Megumi; Sugai,Takeshi; Tamura,Hiroomi

doi:10.3892/mmr.2018.9045

Effect of hesperetin derivatives on the development of selenite‑induced cataracts in rats

Authors:
- Yosuke Nakazawa
- Martin Pauze
- Kazuya Fukuyama
- Noriaki Nagai
- Megumi Funakoshi‑Tago
- Takeshi Sugai
- Hiroomi Tamura
View Affiliations

Affiliations: Faculty of Pharmacy, Keio University, Tokyo 105‑8512, Japan, Faculty of Pharmacy, Kindai University, Osaka 577‑8502, Japan
Published online on: May 22, 2018 https://doi.org/10.3892/mmr.2018.9045
Pages: 1043-1050

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

Cataracts are a major cause of blindness worldwide. As anti‑cataract pharmaceutical therapies require long‑term treatment, identifying anti‑cataract compounds that are ubiquitous in the human diet, have no adverse effects and are affordable, is of paramount importance. The present study focused on hesperetin and its derived compounds, hesperetin stearic acid ester (Hes‑S) and hesperetin oleic acid ester (Hes‑O), in order to investigate their therapeutic potential to treat cataracts in a selenite animal model. Thirteen‑day‑old Sprague Dawley rats were divided into 12 groups. Animals in groups 1 and 7 were subcutaneously injected with vehicle, those in groups 2 and 8 were administered hesperetin, those in groups 3 and 9 received stearic acid, those in groups 4 and 10 were injected with oleic acid, those in groups 5 and 11 were administered Hes‑S, and those in groups 6 and 12 received Hes‑O (10 nmol/kg body weight on days 0, 1 and 2). Animals in groups 7 to 12 were treated with sodium selenite (20 µmol/kg body weight given 4 h following the test compound treatment on day 0) to induce cataract. On day 6, rats had less severe central opacities and lower stage cataracts than rats in the selenite treatment‑only control groups. The levels of glutathione (GSH) and ascorbic acid (AsA) in lenses with selenite‑induced cataracts declined to one‑third of that of controls, and the reduction in GSH and AsA levels was rescued following hesperetin, Hes‑S or Hes‑O treatment, with concentrations remaining to 70‑80% of that of controls. However, there were no changes in the plasma levels of GSH and AsA following treatments. Administration of either hesperetin or hesperetin‑derived compounds prevented the reduction of chaperone activity in the lens, and rats treated with Hes‑S or Hes‑O treatment had significantly greater chaperone activity than hesperetin‑treated rats. Collectively, these results suggested that hesperetin and hesperetin‑derived compounds may be novel drug compounds that have the potential to prevent or delay the onset of cataracts.

View Figures

View References

1	Khairallah M, Kahloun R, Bourne R, Limburg H, Flaxman SR, Jonas JB, Keeffe J, Leasher J, Naidoo K, Pesudovs K, et al: Number of people blind or visually impaired by cataract worldwide and in world regions, 1990 to 2010. Invest Ophthalmol Vis Sci. 56:6762–6769. 2015. View Article : Google Scholar : PubMed/NCBI
2	Liu YC, Wilkins M, Kim T, Malyugin B and Mehta JS: Cataract. Lancet. 390:600–612. 2017. View Article : Google Scholar : PubMed/NCBI
3	Bergamini CM, Gambetti S, Dondi A and Cervellati C: Oxygen, reactive oxygen species and tissue damage. Curr Pharm Des. 10:1611–1626. 2004. View Article : Google Scholar : PubMed/NCBI
4	Pau H, Graf P and Sies H: Glutathione levels in human lens: Regional distribution in different forms of cataract. Exp Eye Res. 50:17–20. 1990. View Article : Google Scholar : PubMed/NCBI
5	Kamei A: Glutathione levels of the human crystalline lens in aging and its antioxidant effect against the oxidation of lens proteins. Biol Pharm Bull. 16:870–875. 1993. View Article : Google Scholar : PubMed/NCBI
6	Nakazawa Y, Oka M, Bando M, Inoue T and Takehana M: The role of ascorbic acid transporter in the lens of streptozotocin-induced diabetic rat. Biomed Prev Nutr. 1:43–48. 2011. View Article : Google Scholar
7	Grey AC, Demarais NJ, West BJ and Donaldson PJ: A quantitative map of glutathione in the aging human lens. Int J Mass Spectrom. (In press).
8	Nakazawa Y, Oka M, Bando M and Takehana M: Hesperetin prevents selenite-induced cataract in rats. Mol Vis. 21:804–810. 2015.PubMed/NCBI
9	Nakazawa Y, Oka M, Tamura H and Takehana M: Effect of hesperetin on chaperone activity in selenite-induced cataract. Open Med (Wars). 11:183–189. 2016.PubMed/NCBI
10	Jeong TS, Kim EE, Lee CH, Oh JH, Moon SS, Lee WS, Oh GT, Lee S and Bok SH: Hypocholesterolemic activity of hesperetin derivatives. Bioorg Med Chem Lett. 13:2663–2665. 2003. View Article : Google Scholar : PubMed/NCBI
11	Ishimori N, Oguchi J, Nakazawa Y, Kobata K, Funakoshi-Tago M and Tamura H: Roasting enhances the anti-cataract effect of coffee beans: Ameliorating Selenite-induced cataracts in rats. Curr Eye Res. 42:864–870. 2017. View Article : Google Scholar : PubMed/NCBI
12	Sedlak J and Lindsay RH: Estimation of total, protein-bound and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 25:192–205. 1968. View Article : Google Scholar : PubMed/NCBI
13	Nakazawa Y, Nagai N, Ishimori N, Oguchi J and Tamura H: Administration of antioxidant compounds affects the lens chaperone activity and prevents the onset of cataracts. Biomed Pharmacother. 95:137–143. 2017. View Article : Google Scholar : PubMed/NCBI
14	Manikandan R, Thiagarajan R, Beulaja S, Sudhandiran G and Arumugam M: Effect of curcumin on selenite-induced cataractogenesis in Wistar rat pups. Curr Eye Res. 35:122–129. 2010. View Article : Google Scholar : PubMed/NCBI
15	Aydemir O, Güler M, Kaya MK, Deniz N and Üstündağ B: Protective effects of ebselen on sodium-selenite-induced experimental cataract in rats. J Cataract Refract Surg. 38:2160–2166. 2012. View Article : Google Scholar : PubMed/NCBI
16	Hwang SL and Yen GC: Effect of hesperetin against oxidative stress via ER- and TrkA-mediated actions in PC12 cells. J Agric Food Chem. 59:5779–5785. 2011. View Article : Google Scholar : PubMed/NCBI
17	St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jäger S, Handschin C, Zheng K, Lin J, Yang W, et al: Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell. 127:397–408. 2006. View Article : Google Scholar : PubMed/NCBI
18	Lu X, Kambe F, Cao X, Kozaki Y, Kaji T, Ishii T and Seo H: 3beta-Hydroxysteroid-delta24 reductase is a hydrogen peroxide scavenger, protecting cells from oxidative stress-induced apoptosis. Endocrinology. 149:3267–3273. 2008. View Article : Google Scholar : PubMed/NCBI
19	Effros RM and Mason GR: Measurements of pulmonary epithelial permeability in vivo. Am Rev Respir Dis. 127:S59–S65. 1983.PubMed/NCBI
20	Schneeberger EE: Airway and alveolar epithelia cell junctionsThe lung: Scientific foundations. Crystal RG, West JB, Barnes PJ, Cherniack NS and Weibel ER: Raven Press; New York: pp. 205–214. 1991
21	Ohtsuki K, Abe A, Mitsuzuwi H, Kondo M, Uemura K, Iwasaki Y and Kondo Y: Effects of long-term administration of hesperidin and glucosyl hesperidin to spontaneously hypertensive rats. J Nutr Sci Vitaminol (Tokyo). 48:420–422. 2002. View Article : Google Scholar : PubMed/NCBI
22	Miwa Y, Mitsuzumi H, Sunayama T, Yamada M, Okada K, Kubota M, Chaen H, Mishima Y and Kibata M: Glucosyl hesperidin lowers serum triglyceride level in hypertriglyceridemic subjects through the improvement of very low-density lipoprotein metabolic abnormality. J Nutr Sci Vitaminol (Tokyo). 51:460–470. 2005. View Article : Google Scholar : PubMed/NCBI
23	Parhiz H, Roohbakhsh A, Soltani F, Rezaee R and Iranshahi M: Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: An updated review of their molecular mechanisms and experimental models. Phytother Res. 29:323–331. 2015. View Article : Google Scholar : PubMed/NCBI