Grape Seed Proanthocyanidin Alleviates Oxidative Stress and Apoptosis Involved in Liver of Hyperthyroid Mice

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Maha Abdulrahman Aldubayan


Objectives: Thyroid hormones control the basal metabolic pace of hepatocytes, and can make oxidative harm hepatic frameworks. The reason for this investigation was to investigate how hyperthyroidism-prompted liver danger, oxidative pressure and apoptosis changes could be alleviated with Grape seed proanthocyanidin extract (GSPE). This investigation assessed some biochemical, histological and immunohistochemical changes in post pubertal hyperthyroidism and its effect on liver capacity and structures. Notwithstanding the enhancing job of Grape seed proanthocyanidin remove (GSPE) supplementation was analyzed.

Materials and Methods: Fifty male Swiss albino mice were randomly divided into 5 groups (G1, Control; G2, GSPE; G3, Eltroxin-induced hyperthyroid mice; G4, Post treated hyperthyroid with GSPE; G5, Self-treated hyperthyroid mice).

Results: Our results revealed that, a significant increase in serum T3, T4, ALT, AST, ALP, liver MDA, P53 levels, injury and P53 expression in hyperthyroid mice when compared to control and GSPE. In contrast; serum albumin, liver catalase, GSH, SOD and Bcl2 were decrease in hyperthyroid mice. Treatment of hyperthyroid mice with GSPE advantages in improving the adverse effect of hyperthyroidism and moreover the histopathological and P53 expression result approves this finding.

Conclusions: GSPE can be used in hyperthyroidism treatment to help propylthiouracil or carbimazole or methimazole therapy.

Hyperthyroidism, grape seed proanthocyanidin, hepatic dysfunction, oxidative stress, liver injury and PCNA

Article Details

How to Cite
Aldubayan, M. A. (2019). Grape Seed Proanthocyanidin Alleviates Oxidative Stress and Apoptosis Involved in Liver of Hyperthyroid Mice. Annual Research & Review in Biology, 33(6), 1-11.
Original Research Article


Joeimon JL, Mohanraj K, Karthikeyan R, et al. Thyroid dysfunction in patients with liver cirrhosis. Journal of Dental and Medical Sciences 2017; 16(4):18-22.

Beltagy D, Mohamed T, El Said A, Tousson E. Beneficial role of ascorbic and folic acids antioxidants against thyroxin-induced testicular dysfunction in hyperthyroid rats. Environmental Science and Pollution Research. 2016;23(17): 17246-54.

Salama A, Tousson E, Ebrahim W, Elwan M. Ameliorating role of folic acid in eltroxine induced hyperthyroid and oxidative stress in rat cortex, hypoth-alamus and hippocampus. Alexandria Journal of Veterinary Sciences 2017;55(1): 210-216.

Tousson E, Ali EM, Ibrahim W, Mansour MA. Proliferating cell nuclear antigen as a molecular biomarker for spermatogenesis in PTU-induced hypothyroidism of rats. Reprod Sci. 2011;18:679-686.

Tousson E, Ali EM, Ibrahim W, Mansour MA. Treatment with folic acid ameliorated the histopathological alterations caused by propylthiouracil-induced hypothyroid rat testes. Toxicology and Industrial Health. 2012;28:566–576.

Tousson E, Ali EM, Ibrahim W, Ashraf RM. Histopathological and immunohisto chemical alterations in rat heart after thyroidectomy and the role of hemin and ketoconazole in treatment. Biomedicine & Pharmacotherapy. 2012;66:627–632.

Tousson E, Hafez E, Massoud A, Sweef O, Atta N. Protective role of folic acid in thyroxine-induced cardiac hypertrophy in hyperthyroid rat. Biomedicine & Aging Pathology. 2013;3:89–95.

Tousson E, Hafez E, Zaki S, Gad A. P53, Bcl-2 and CD68 expression in response to amethopterin-induced lung injury and ameliorating role of l-carnitine. Biomedicine & Pharmacotherapy. 2014;8(5):631–639.

Tousson E, Hafez E, Zaki S, Gad A. The cardioprotective effects of L-carnitine on rat cardiac injury, apoptosis and oxidative stress caused by amethopterin. Environ Sci Pollut Res. 2016;23:20600–20608.

Kim D. et al. Subclinical hypothyroidism and low-normal thyroid function are associated with nonalcoholic steatohe-patitis and fibrosis. Clin. Gastroenterol. Hepatol. 2018;16:123–131.

Aydemir S, Bayraktaroglu T, Demircan N, Sert M, Açikgoz S, Tekin IO, et al . Effect of hyperthyroidism and propylthiouracil treatment on liver biochemical tests. Int J Clin Pract. 2005;59(11):1304-1308.

Mansourian AR. A review of literatures on the adverse effects of thyroid abnormalities and liver disorders: An overview on liver dysfunction and hyperthyroidism. P J Biological Science. 2013;16: 1641-1652.

Bolkiny Y, Tousson E, El-Atrsh A, Akela M, Farg E. Costus root extract alleviates blood biochemical derangements of experi-mentally induced hypo- and hyperthyro-idism in mice. Annual Research & Review in Biology. 2019;31(5):1-0.

Sinha RA, Yen PM. Thyroid hormone-mediated autophagy and mitochondrial turnover in NAFLD. Cell Biosci. 2016;6:46.

Khemichian S, Ling Fong T. Hepatic Dysfunction in Hyperthyroidism. Gastro enterol Hepatol. 2011;7(5):337–339.

Bagchi D, Swaroop A, Preuss HG, Bagchi M. Free radical scavenging, antioxidant and cancer chemoprevention by grape seed proanthocyanidin: An overview. Mutat Res. 2014;768:69-73.

Li SG, Ding YS, Niu Q, Xu SZ, Pang LJ, Ma RL, Jing MX, Feng GL, Liu JM, Guo SX. Grape seed proanthocyanidin extract alleviates arsenic-induced oxidative reproductive toxicity in male mice. Biomed Environ Sci. 2015;28:272–280.

Schelz Z, Ocsovszki I, Bózsity N, Hohmann J, Zupko I. Antiproliferative effects of various furanoacridones isolated from Ruta graveolens on human breast cancer cell lines. Anticancer Res. 2016;36: 2751–2758.

Sarshar S, Brandt S, Asadi Karam MR, Habibib M, Bouzari S, Lechtenberg M, Dobrindt U, Qin X, Goycoolea FM, Hensel A. Aqueous extract from Orthosiphon stamineus leaves prevents bladder and kidney infection in mice. Phytomedicine 2017;28:1–9

Zhou K, Raffoul JJ. Potential anticancer properties of grape antioxidants. J Oncol 2015;80:3294.

Al-Rasheed NM, El-Masry TA, Tousson E, Hassan H, Al-Ghadeer A. Protective potential of grape seed proanthocyandins extract against glivec (Imatinib Mesylate) induced liver toxicity and oxidative stress in male rats. Annual Research & Review in Biology. 2017;20(6):1-9.

Zhu FM, Du B, Li J. Effect of ultrafine grinding on physicochemical and anti-oxidant properties of dietary fiber from wine grape pomace. Food Sci Technol Int. 2014;20:55–62.

El-Atrash A, Zaki S, Tousson E, Shoir M. Protective potential of grape seed extract against monosodium glutamate induced liver toxicity and oxidative stress in young rats. Journal of Advanced Trends in Basic and Applied Science. 2017;1(3):257-262.

Al-Naely A, Shattnan D. Effect of grape seed extract on biochemical factor and histological changes in liver and the kidney in albino rat infected hypo- hyperthyroidism induced laboratory by carbimazole and l-thyroxine. Journal of Global Pharma Technology. 2017;9(9):174-181

Thakur C, Saikia TC, Yadav RN. Total serum levels of triiodothyronine (T3) thyroxine (T4) and thyrotropine (TSH) in school going children of Dibrugarh district: an endemic goitre region of Assam. Indian J Physiol Pharmacol. 1997;41(2):167-70.

Ibrahim W, Tousson E, Ali EM, Mansour MA. Folic acid alleviates oxidative stress and hyperhomocysteinemia involved in testicular dysfunction of hypothyroid rats. General and comparative endocrinology. 2011 Nov 1;174(2):143-9.

Ibrahim W, Tousson E, El-Masry T, Arafa N, Akela M. The effect of folic acid as an antioxidant on the hypothalamic monoamines in experimentally induced hypothyroid rat. Toxicology and industrial health. 2012;28(3):253-61.

El-Moghazy M, Zedan NS, El-Atrsh AM, El-Gogary M, Tousson E. The possible effect of diets containing fish oil (omega-3) on hematological, biochemical and histopathogical alterations of rabbit liver and kidney. Biomedicine & Preventive Nutrition. 2014 Jul 1;4(3):371-7.

Doumas BT, Watson WA, Biggs HG. Albumin standards and the measurement of serum albumin with bromocresol green. Clin Chim Acta. 1977;31:87–96.

Moss DW, Henderson AR. Clinical enzymology CA Burtis, ER Ashwood (Eds.). Tietz Textbook of Clinical Chemistry (3rd Ed) 1999. W.B Saunders Company, Philadelphia. 1999;617- 721.

Moustafa AH, Ali EM, Moselhey SS, Tousson E, El-Said KS. Effect of coriander on thioacetamide-induced hepatotoxicity in rats. Toxicology and industrial health. 2014;30(7):621-9.

Saggu S, Sakeran MI, Zidan N, Tousson E, Mohan A, Rehman H. Ameliorating effect of chicory (Chichorium intybus L.) fruit extract against 4-tert-octylphenol induced liver injury and oxidative stress in male rats. Food and chemical toxicology. 2014;72:138-146.

Misra HP, Fridovich I. The role of superoxide anion in the auto-oxidation of epinephrine and a simple assay for super oxidedismutase. Jornal of Biológica Chemsitry. 1972;247: 3170- 3175.

Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J. Lab. Clin. Med. 1963;61: 882–888.

Tousson E, Rafat BM, Hessien M, El Barbary AA, Sami A. P53 and Bcl2 apoptosis proteins in meso-2, 3-dimercaptosuccinic acid treated lead-intoxicated rabbits. Toxicology and Industrial Health. 2011;27(3):271-8.

Tousson E. Histopathological alterations after a growth promoter boldenone injection in rabbits. Toxicology and Industrial Health 2016;32(2):299-305.

Abd Eldaim MA, Tousson E, El Sayed IE, Awd WM. Ameliorative effects of Saussurea lappa root aqueous extract against Ethephon‐induced reproductive toxicity in male rats. Environmental Toxicology. 2019;34(2):150-9.

Giannini EG, Testa R and Savarino V. Liver enzyme alteration: A guide to clinicians. MAJ. 2005;172(3):367-79.

Hull K, Horenstein R, Naglieri R, Munir K, Ghany M, Celi FS. Two cases of thyroid storm associated cholestatic jaundice. Endocr Pract. 2007;13:476-480.

Biscoveanu M, Hasinski S. Abnormal results of liver function test in patients with Grave’s disease. Endocr Pract. 2000;6: 367-369.

Wang R, Tan J, Zhang G, Zheng W, Li C. Risk factors of hepatic dysfunction in patients with Graves’ hyperthyroidism and the efficacy of 131iodine treatment. Medicine. 2017;96:5(6035).

Upadhyay G, Singh R, Kumar A, Kumar S, Kapoor A, God bole MM. Severe hyperthyroidism induces mitochondria mediated apoptosis in rat liver. Hepatology. 2004;39(4):1120-1130.

Tousson E, Elgharabawy RM, Elmasry TA. Grape seed proanthocyanidin ameliorates cardiac toxicity induced by boldenone undecylenate through inhibition of nadph oxidase and reduction in the expression of NOX2 and NOX4. Oxidative Medicine and Cellular Longevity. 2018;9434385.

Kandemir FM, Benzer F, Ozkaraca M, Ceribasi S, Yildirim NC, Ozdemir N. Protective antioxidant effects of grape seed extract in a cisplatin-induced hepatotoxicity model in rabbits. Revue Méd. 2012;163(11):539-545.

Sahoo D, Roy A, Bhanja S, Chainy G. Hypothyroidism impairs antioxidant defence system and testicular physiology during development and maturation. General Comp Endocrinol. 2008;156:63–70.

Das K, Chainy GN. Modulation of rat liver mitochondrial antioxidant defence system by thyroid hormone. Biochim Biophys Acta. 2001;1537:1-13.

Kumar A, Sinha RA, Tiwari M , Singh R, Koji T, Manhas N, Rastogi L, Pal L, Shrivastava A, Sahu RP, Godbole MM. Hyperthyroidism induces apoptosis in rat liver through activation of death receptor-mediated pathwaysq. Journal of Hepatology. 2007;46:888–898.

Asayama K, Kato K. Oxidative muscular injury and its relevance to hyperthyroidism. Free Radic Biol Med. 1990;8:293-303.

Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray SD, Kuszynski CA, Joshi SS, Pruess HG. Free radicals and grape seed proanthocyanidin extract: Importance in human health and disease prevention. Toxicology. 2000;148:187–197.

Davies KJ. Oxidative stress, antioxidant defenses and damage removal, repair, and replacement systems. IUBMB Life. 2000; 50:279-289.

Chattopadhyay S, Sahoo DK, Subudhi U, Chainy GB. Differential expression profiles of antioxidant enzymes and glutathione redox status in hyperthyroid rats: A temporal analysis. Comp. Biochem. Physiol C Pharmacol Toxicol Endocrinol. 2007;146:383-391.

Long M, Yang S, Han J, Li P, Zhang Y, Dong S. The protective effect of grape-seed proanthocyanidin extract on oxidative damage induced by zearalenone in kunming mice liver. Int J Mol Sci. 2016;17(6):808.

Diebold J, Baretton G, Felchner M, Meier W, Dopper K, Schmidt M, Lohrs U. Bcl-2 expression, p53 accumulation, and apoptosis in ovaria carcinomas. Am J Clin Patho.l 1996;105:341–334.

Eldaim MA, Tousson E, El Sayed IE, El AE, Elsharkawy HN. Grape seeds proanthocyanidin extract ameliorates Ehrlich solid tumor induced renal tissue and DNA damage in mice. Biomedicine & Pharmacotherapy. 2019;115:108908.

Tousson E, Hafez E, Massoud A, Sweef O, Atta N. Protective role of folic acid in thyroxine-induced cardiac hypertrophy in hyperthyroid rat. Biomedicine & Aging Pathology. 2013;3:89–95.