Protective Effects of Grape Molasses and Resveratrol Against DMBA Induced Oxidative Stress in Rat Ovarian Tissues

Year 2019, Volume: 5 Issue: 2, 151 - 159, 28.08.2019

Tuğba Raika Kıran , Onder Otlu , Ercan Karabulut Aysun Bay Karabulut

https://doi.org/10.19127/mbsjohs.595016

Cited By: 1

Abstract

Objective:
The polyphenolic compound, resveratrol (3, 4’, 5-trihydroxystilbene),
trans-resveratrol is a natural phytoalexin that exists in many different foods
such as grape peel and seed, peanut, mulberry and blueberry. Molasses is a
natural food obtained by boiling and concentrating fruit juices known to be
rich in minerals such as iron, phosphorus, potassium, sodium, calcium and
magnesium, and phosphoric acid, formic acid, organic acids and some vitamins.
Polyphenolic compounds are natural antioxidants and are known to have
protective effects against tissue damage caused by reactive oxygen species
(ROS). In this study, we aimed to investigate the protective effects of grape
molasses and resveratrol on ovarian damage induced by 7, 12-dimethylbenz [a]
anthracene (DMBA).

Methods:
A total of 42 old female Wistar Albino rats, aged 18 weeks were divided into
six groups. 10 mg/kg DMBA was injected in the rats in DMBA group subcutaneously
on day 0 and day 7 while grape molasses feed with 20% grape molasses was given
along with DMBA application to the rats in DMBA + grape molasses group.
Resveratrol was administered by subcutaneous injection at 10 mg/kg/day to the
DMBA + Resveratrol group, while only feed with 20% grape molasses was given to
the grape molasses group. Resveratrol was administered by subcutaneous
injection at 10 mg/kg/day to the resveratrol group.

Results:
GSH activity between the control group and molasses group,
DMBA and DMBA + molasses groups and the control group and the DMBA + grape
molasses groups was found statistically significant. Regarding the NO activity,
the difference between the DMBA and resveratrol groups, DMBA and DMBA +
resveratrol groups and the grape molasses and resveratrol groups was found
statistically significant. MDA activity between DMBA + resveratrol and DMBA +
grape molasses groups, and DMBA + grape molasses and grape molasses groups was
found statistically significant.

Conclusion:
Molasses as one of the most important nutrient sources of
Eastern and Central Anatolia was observed to decrease ovarian tissue oxidative
damage induced with DMBA compared to resveratrol.

Keywords

DMBA, resveratrol, grape molasses, oxidative stress, ovarian

References

• Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y. Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Research. 2004; 24: 2783-2840.
• Al Fatease A, Shah V, Nguyen DX, Cote B, LeBlanc N, Rao DA, Alani AW. Chemosensitization and mitigation of Adriamycin-induced cardiotoxicity using combinational polymeric micelles for co-delivery of quercetin/resveratrol and resveratrol/curcumin in ovarian cancer. Nanomedicine. 2019; 19: 39-48.
• Armstrong BG, Hutchinson E, Unwin J, Fletcher T. Lung Cancer Risk after Exposure to Polycyclic Aromatic Hydrocarbons: A Review and Meta-Analysis. Environ Health Perspect. 2004; 112: 970-978.
• Batu A, Kucuk E, Cimen M. Determination of the Physicochemical and Biochemical Values of Flower Honeys Obtained from Eastern Anatolia and Eastern Black Sea Regions. The Association of Food Technology. 2013; 8: 52-62.
• Chanvitayapongs S, Draczynska - Lusiak B, Sun AY. Amelioration of oxidative stress by antioxidants and resveratrol in PC12 cells. Neuro Report. 1997; 8: 1499-1502.
• Chen HY, Lin PH, Shih YH, Wang KL, Hong YH, Shieh TM, et al. Natural Antioxidant Resveratrol Suppresses Uterine Fibroid Cell Growth and Extracellular Matrix Formation In Vitro and In Vivo. Antioxidants (Basel). 2019; 8: 99.
• Cortas NK, Wakid NW. Determination of inorganic nitrate in serum and urine by a kinetic cadmium reduction method. Clin Chem. 1990; 36: 1440-1443.
• David H. Phillips. Polycyclic aromatic hydrocarbons in the diet. Mutation Research. 1999; 443:139-147.
• De-la-Lastra CA, Villegas I. Resveratrol as an anti-inflammatory and anti-aging agent: Mechanisms and clinical implications. Molecular Nutrition & Food Research. 2005; 49: 405-430.
• De La Lastra CA, Villages I. Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications. Biochemsoc trans. 2007; 35:1156-1160.
• Ebeler SE, Brenneman CA, Kim GS, Jewell WT, Webb MR, Leticia CR, et al. Dietary catechin delays tumor onset in a transgenic mouse model. American Journal of Clinical Nutrition. 2002; 76: 865-872.
• Eng ET, Ye J, Williams D, Phung S, Moore RE, Young MK, et al. Suppression of estrogen biosynthesis by procyanidin dimers in red wine and grape seeds. Cancer Res. 2003; 63: 8516-8522.
• Francischi JN, Frade TIC, Almeida MPA, Queiroz BFG, Bakhle YS. “Ketamine-xylazine anaesthesia and orofacial administration of substance P: a lethal combination in rats,” Neuropeptides. 2017; 62: 21–26.
• Gao J, Lauer FT, Mitchell LA, Burchiel SW. Microsomal Expoxide Hydrolase Is Required for 7,12-Dimethylbenz[a]anthracene (DMBA)–Induced Immunotoxicity in Mice. Toxicological Sciences. 2007; 98: 137-144.
• Garvin S, Ollinger K, Dabrosin C. Resveratrol induces apoptosis and inhibits angiogenesis in human breast cancer xenografts in vivo. Cancer Letters. 2006; 231: 113-122.
• Giovanni DJ, Juchau MR. Biotransformation and bioactivation of 7, 12 dimethylbenz (a) anthracene (7,12-DMBA). Drug Metab. 1980; 11: 61-101.
• Im J, Kim H, Kim B, Yun J, Lee J, Lee C. A study on the characteristics of pollutant release and transfer registers (PRTRs) and cancer incidence rates in Korea. Environ Sci Pollut Res Int. 2019; 26: 17080-17090.
• Jung KJ, Wallig MA, Singletary KW. Purple grape juice inhibits 7, 12- dimethylbenz [a] anthracene (DMBA)-induced rat mammary tumorigenesis and in vivo DMBA-DNA adduct formation. Cancer Lett. 2006; 233:279-288.
• Katiyar SK. Grape seed proanthocyanidins and skin cancer prevention: inhibition of oxidative stress and protection of immune system. Molecular Nutrition and Food Research. 2008; 52: 71-76.
• Kijima I, Phung S, Hur G, Kwok SL, Chen S. Grape seed extract is an aromatase inhibitor and a suppressor of aromatase expression. Cancer Res. 2006; 66: 5960-5967.
• Kim H, Hall P, Smith M, Kirk M, Prasain JK, Barnes S, et al. Chemoprevention by Grape Seed Extract and Genistein in Carcinogen induced Mammary Cancer in Rats Is Diet Dependent. International Research Conference on Food, Nutrition and Cancer J Nutr. 2004; 134: 3445-3452.
• Krishna PL, Pezzuto B, Pezzuto JM. Cancer Chemopreventive Activity of Resveratrol. Annals New York Academy Science. 2002; 957:210-229.
• Leonard SS, Xia C, Jiang BH, Stinefelt B, Klandorf H, Harris GK, Shi X. Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem Biophys Res Commun. 2003; 309:1017–1026.
• Lopez-Oliva ME, Agis-Torres A, Goni I, Munoz – Martinez E. Grape antioxidant dietary fibre reduced apoptosis and induced a pro-reducing shift in the glutathione redox state of the rat proximal colonic mucosa. British Journal of Nutrition. 2010; 103: 1110-1117.
• Pacheco de Jesus GP, Ribeiro FAP, Gomes de Moura CF, Gollucke APB, Oshima CTF, Ribeiro DA. Anti-tumor activity of grape juice concentrate in the rat tongue two-stage initiation–promotion protocol induced by 4-nitroquinoline 1-oxide. Toxicol Mech Methods. 2014; 24: 276.
• Park YK, Park E, Kim JS, Kang MH. Daily grape juice consumption reduces oxidative DNA damage and plasma free radical levels in healthy Koreans. Mutation Research. 2013; 529: 77-86.
• Pharm RPB, Sahni JK, Ali J, Sharma S, Baboota S. Resveratrol: review on the rapeutic potential and recent advances in drug delivery. Expert Opin Drug Deliv.2014; 11: 1285-1298.
• Santos AC, Pereira I, Magalhães M, Pereira-Silva M, Caldas M, Ferreira L, Figueiras A, Ribeiro AJ, Veiga F. Targeting Cancer Via Resveratrol-Loaded Nanoparticles Administration: Focusing on In Vivo Evidence. The AAPS Journal. 2019; 21: 57. Schlachterman A, Valle F, Wall KM, Azios NG, Castillo L, Morell L et al. Combined resveratrol, quercetin, and catechin treatment reduces breast tumor growth in a nude mouse model. Translational Oncology. 2008; 1: 19-27.
• Shafiee M, Carbonneau MA, Urban N, Descomps B, Leger CL. Grape and grape seed extract capacities at protecting LDL against oxidation generated by Cu2+, AAPH or SIN1 and at decreasing superoxide THP-1 cell production. A comparison to other extracts or compounds. Free Radical Research. 2003; 37: 573-584.
• Singh T, Sharma SD, Katiyar SK. Grape proanthocyanidins induce apoptosis by loss of mitochondrial membrane potential of human non-small cell lung cancer cells in vitro and in vivo. Plos One. 2011; 6: e27444
• Souza CF, Baldissera MD, Descovi SN, Zeppenfeld CC, Verdi CM, Santos RCV, et al. Grape pomace flour alleviates Pseudomonas aeruginosa-induced hepatic oxidative stress in grass carp by improving antioxidant defense. Microb Pathog. 2019;129:271-276.
• Sun Q, Prasad R, Rosenthal E, Katiyar SK. Grape seed proanthocyanidins inhibit the invasive potential of head and neck cutaneous squamous cell carcinoma cells by targeting EGFR expression and epithelial-to-mesenchymal transition. BMC Complementary and Alternative Medicine. 2011; 11: 134.
• Tietze F, Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem. 1969; 27: 502-522.
• Truong VL, Jun M, Jeong WS. Role of resveratrol in regulation of cellular defense systems against oxidative stress. BioFactors. 2018; 44: 36–49.
• Uchiyama M, Mihara M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978; 86: 271-278.
• Ustun MS, Tosun I. The Composition of Pekmez. The JOurnal of Foodç 1997; 22: 417-423.
• Yu Z, Xu W, Wang H. Resveratrol treatment inhibits acute pharyngitis in the mice model through inhibition of PGE2/COX-2 expression. Saudi J Biol Sci. 2018; 25: 1468-1472. Zadi Heydarabad M, Nikasa M, Vatanmakanian M, Azimi A, Farshdousti Hagh M. Regulatory effect of resveratrol and prednisolone on MDR1 gene expression in acute lymphoblastic leukemia cell line (CCRF-CEM): An epigenetic perspective. J Cell Biochem. 2018; 119: 4890-4896.
• Zeweil MM, Sadek KM, Taha NM, El-Sayed Y, Menshawy S. Graviola attenuates DMBA-induced breast cancer possibly through augmenting apoptosis and antioxidant pathway and downregulating estrogen receptors. Environ Sci Pollut Res Int. 2019; 26: 150209-150217.
• Zhao J, Wang J, Chen Y, Agarwal R. Anti-tumor-promoting activity of a polyphenolic fraction isolated from grape seeds in the Mouse skin two-stage initiation-promotion protocol and identification of procyanidin B5-3ʹ -gallate as the most effective antioxidant constituent. Carcinogenesis. 1999; 20: 1737-1745.
• Zheng X, Jia B, Song X, Kong QY, Wu ML, Qiu ZW, Li H, Liu J. Preventive Potential of Resveratrol in Carcinogen-Induced Rat Thyroid Tumorigenesis. Nutrients. 2018; 10: 279.
• Zhou Y, Jin Y, Yu H, Shan A, Shen J, Zhou C, et al. Resveratrol inhibits aflatoxin B1-induced oxidative stress and apoptosis in bovine mammary epithelial cells and is involved the Nrf2 signaling pathway. Toxicon. 2019; 164: 10-15.