Protective Effects of Cydonia oblonga Mill. Fruit on Carbon Tetrachloride-induced Hepatotoxicity Mediated through Mitochondria and Restoration of Cellular Energy Content

Document Type : Research article

Authors

1 Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.

2 School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.

Abstract

Quince (Cydonia oblonga Mill.) is one of the medicinal plant with a broad range of pharmacological activities such as hepatoprotective effect. The present study was conducted to evaluate the effect of aqueous extract of Cydonia oblonga Mill. fruit (ACOF) against carbon tetrachloride (CCl4)-induced liver damage in rats. Hepatotoxicity was induced by CCl4 and all tested group animals were treated with the plant extract at a dose of 75, 150, and 300 mg/kg orally for 5 days. Blood was collected for the assessment of serum marker enzymes (alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH)). Adenosine triphosphate (ATP) of liver mitochondria was also measured using a validated high performance liquid chromatography (HPLC) method. The antioxidant capacity of the extract resulted in the reduction of MDA and the restoration of GSH in the liver (P < 0.05). Free radical scavenging activity of the extract was evaluated by DPPH method and the IC50 value was found to be 568 μg/mL. Our results indicated that bioenergetic depletion occurred in the intoxicated rats as a consequence of mitochondrial dysfunction and ATP production collapse. ACOF markedly restored ATP contents that is a key step in liver regeneration. It can be concluded that the role of ACOF to improve liver function on CCl4-hepatoxicity could be attributed, at least partially, to its action at mitochondira by preventing the loss of ATP content.

Graphical Abstract

Protective Effects of Cydonia oblonga Mill. Fruit on Carbon Tetrachloride-induced Hepatotoxicity Mediated through Mitochondria and Restoration of Cellular Energy Content

Keywords


  • Wills PJ and Asha VV. Protective effect of Lygodium flexuosum (L.) Sw. extract against carbon tetrachloride-induced acute liver injury in rats. Ethnopharmacol. (2006) 108: 320-6.
  • Chandan BK, Saxena AK, Shukla S, Sharma N, Gupta DK, Suri KA, Suri J, Bhadauria M and Singh B. Hepatoprotective potential of Aloe barbadensis Mill. against carbon tetrachloride induced hepatotoxicity. Ethnopharmacol. (2007) 111: 560-6.
  • Singh B, Saxena AK, Chandan BK, Bhardwaj V, Gupta VN, Suri OP and Handa SS. Hepatoprotective activity of indigtone--a bioactive fraction from Indigofera tinctoria Linn. Res. (2001) 15: 294-7.
  • Joshi PP, Patil SD, Silawat N and Deshmukh PT. Effect of Tridax procumbens (Linn.) on bile duct ligation-induced liver fibrosis in rats. Prod. Res. (2011) 25: 1975-81.
  • Jain S, Dixit VK, Malviya N and Ambawatia V. Antioxidant and hepatoprotective activity of ethanolic and aqueous extracts of Amorphophallus campanulatus Roxb. tubers. Acta Pol. Pharm. (2009) 66: 423-8.
  • Fattouch S, Caboni P, Coroneo V, Tuberoso CI, Angioni A, Dessi S, Marzouki N and Cabras P. Antimicrobial activity of Tunisian quince (Cydonia oblonga Miller) pulp and peel polyphenolic extracts. Agric. Food Chem. (2007) 55: 963-9.
  • Pacifico S, Gallicchio M, Fiorentino A, Fischer A, Meyer U and Stintzing FC. Antioxidant properties and cytotoxic effects on human cancer cell lines of aqueous fermented and lipophilic quince (Cydonia oblonga) preparations. Food Chem. Toxicol. (2012) 50: 4130-5.
  • Zhou W, Abdusalam E, Abliz P, Reyim N, Tian S, Aji Q, Issak M, Iskandar G, Moore N and Umar A. Effect of Cydonia oblonga fruit and leaf extracts on blood pressure and blood rheology in renal hypertensive rats. J. Ethnopharmacol. (2014) 152: 464-9.
  • Zhou W, Abdurahman A, Umar A, Iskander G, Abdusalam E, Berké B, Bégaud B and Moore N. Effects of Cydonia oblonga Miller extracts on blood hemostasis, coagulation and fibrinolysis in mice, and experimental thrombosis in rats. Ethnopharmacol. (2014) 154: 163-9.
  • Minaiyan M, Ghannadi A, Etemad M and Mahzouni P. A study of the effects of Cydonia oblonga Miller (Quince) on TNBS-induced ulcerative colitis in rats. Pharm. Sci. (2012) 7: 103-10.
  • Huber R, Stintzing FC, Briemle D, Beckmann C, Meyer U and Gründemann C. In-vitro antiallergic effects of aqueous fermented preparations from Citrus and Cydonia fruits. Planta Med. (2012) 78: 334-40.
  • Ghafourian M, Tamri P and Hemmati A. Enhancement of human skin fibroblasts proliferation as a result of treating with quince seed mucilage. Jundishapur J. Nat. Pharm. Prod. (2015) 10: e18820.
  • Aslan M, Orhan N, Orhan DD and Ergun F. Hypoglycemic activity and antioxidant potential of some medicinal plants traditionally used in Turkey for diabetes. J Ethnopharmacol. (2010) 128: 384-9.
  • Gholami S, Hosseini MJ, Jafari L, Omidvar F, Kamalinejad M, Mashayekhi V, Hosseini SH, Kardan A, Pourahmad J and Eskandari MR. Mitochondria as a Target for the Cardioprotective Effects of Cydonia oblonga and Ficus carica L. in Doxorubicin-Induced Cardiotoxicity. Drug Res (Stuttg) (2017) 67: 358-65.
  • Khademi F, Danesh B, Mohammad Nejad D and Soleimani Rad J. The comparative effects of atorvastatin and quince leaf extract on atherosclerosis. Red Crescent Med. J. (2013) 15: 639-43.
  • Mirmohammadlu M, Hosseini SH, Kamalinejad M, Esmaeili Gavgani M, Noubarani M and Eskandari MR. Hypolipidemic, hepatoprotective and renoprotective effects of Cydonia oblonga fruit in streptozotocin-induced diabetic Rats. Iran. J. Pharm. Res. (2015) 14: 1207-14.
  • Adiban H, Shirazi FH, Gholami S, Kamalinejad M, Hosseini SH, Noubarani M and Eskandari MR. Chemopreventive effect of quince (Cydonia oblonga) fruit extract on hepatocellular carcinoma induced by diethylnitrosamine in rats. Int. Pharm. Acta (2019) 2: 233-43.
  • Aliasl F, Toliyat T, Mohammadi A, Minaee B, Samadi N, Aliasl J and Sadeghpour O. Medicinal properties of Cydonia oblonga mill fruit (pulp and peel) in Iranian traditional medicine and modern phytothrapy. Integr. Med. (2016) 1: 122-8.
  • Hernández-Muñoz R, Díaz-Muñoz M,Suárez-Cuenca JA, Trejo-Solís C, López V, Sánchez-Sevilla L, Yáñez L and De Sánchez VC. Adenosine reverses a preestablished CCl4 induced micronodular cirrhosis through enhancing collagenolytic activity and stimulating hepatocyte cell proliferation in rats. Hepatology (2001) 34: 677-87.
  • Blainski A, Lopes GC and Pallazo . Application and analysis of the folin ciocalteu method for the determination of the total phenolic content from Limonium brasiliense Molecules (2013) 18: 6852-65.
  • Chang C, Yang M, Wen H and Chern J. Estimation of total flavonoid content in propolis by two complementary colorimetric methods. Food Drug Anal. (2002) 10: 178–82.
  • Wang, M, Li J, Rangarajan M, Shao Y, Lavoie E, Huang T and Ho CT. Antioxidative phenolic compounds from sage (Salvia officinalis). Agric. Food Chem. (1998) 46: 4869–73.
  • Noubarani M, Khayat SA, Mafinezhad R, Mohebbi S, Mohammad K, Andalib S, Kardan A and Eskandari MR. Protective effect of Cydonia oblonga fruit on carbon tetrachloride-induced hepatotoxicity. Planta Med. (2016) 81: S1-S381.
  • Lambowitz AM. Preparation and analysis of mitochondrial ribosomes. Methods Enzymol. (1979) 59: 421-33.
  • Smith MT, Thor H, Hartizell P and Orrenius S. The measurement of lipid peroxidation in isolated hepatocytes. Biochem. Pharmacol. (1982) 31: 19-26.
  • Riener C, Kada G and Gruber HJ. Quick measurement of protein sulfhydryls with Ellman’s reagent and with 4,4-dithiodipyridine. Bioanal. Chem. (2002) 373: 266–76.
  • Nieminen AL, Qian T, Trost LC, Elmore SP, Nishimura Y, Crowe RA, Cascio WE, Bradham CA, Brenner DA and Herman B. The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Biophys. Acta (1998) 1366: 177-96.
  • Mehendale HM. Role of hepatocellular regeneration and hepatolobular healing in the final outcome of liver injury — a two-stage model of toxicity. Pharmacol. (1991) 42: 1155-62.
  • Asha VV. Preliminary studies on the hepatoprotective activity of Mamordica subangulata and Naragamia alata. Indian J. Pharmacol. (2001) 33: 276-9.
  • Ploa, GL and Hewitt WR. Detection and evaluation of chemically induced liver injury. In: Wallace Hayes A. (ed.). Principles and Methods of Toxicology. 2nd ed. Raven Press, New York (1989) 399-628.
  • Boll M, Weber LW, Becker E and Stampfl A. Mechanism of carbon tetrachloride-induced hepatotoxicity. Hepatocellular damage by reactive carbon tetrachloride metabolites. Naturforsch. C. J. Biosci. (2001) 56: 649-59.
  • Shih PH, Hsu CL and Yen GC. Hepatoprotection of tea seed oil (Camellia oleifera Abel.) against CCl4-induced oxidative damage in rats. Food Chem. Toxicol. (2007) 45: 888-95.
  • Srivastava A and Shivanandappa T. Hepatoprotective effect of the aqueous extract of the roots of Decalepis hamiltonii against ethanol-induced oxidative stress in rats. Res. (2006) 35: 267-75.
  • Jain A, Soni M, Deb L, Jain A, Rout SP, Gupta VB and Krishna KL. Antioxidant and hepatoprotective activity of ethanolic and aqueous extracts of Momordica dioica leaves. J. Ethnopharmacol. (2008) 115: 61-6.
  • Silva BM, Andrade PB, Ferreres F, Domingues AL, Seabra RM and Ferreira MA. Phenolic profile of quince fruit (Cydonia oblonga) (pulp and peel). J. Agric. Food Chem. (2002) 50: 4615-8.