Hepatoprotective activity of aerial parts of Otostegia persica against carbon tetrachloride-induced liver damage in rats

Document Type: Original Research Article

Authors

1 Social Determinants of Health Research Center, Yasuj University of Medical Sciences, Yasuj, Iran

2 Student Research Committee, Yasuj University of Medical Sciences, Yasuj, Iran

3 Cellular and Molecular Research Center, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran

4 Department of Pharmacology, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran

5 Student Research Committee, Yasuj University of Medical Sciences, Yasuj, Iran

Abstract

Objective: To evaluate the hepatoprotective properties of Otostegia persica (O. persica) ethanol extract on carbon tetrachlo‌‌ride-induced liver damage in rats.
Materials and Methods: Fifty adult male Wistar rats were randomly divided into five groups. Group I served as normal control and was given only olive oil intraperitoneally (i.p.). Group II, III, IV, and V were administered CCl4 mixed with olive oil 1:1 (1 ml/kg) i.p., twice a week for 8 weeks. Group II was maintained as CCl4-intoxicated control (hepatotoxic group). Group III, IV, and V received O. persica extract at a dose of 40, 80, and 120 mg/kg for 8 weeks every 48 h orally, respectively. Biochemical parameters including aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TB), albumin (ALB), total protein (TP), and lipid peroxidation marker (Malonaldialdehyde, (MDA) were determined in serum. After 8 weeks, animals were sacrificed, livers dissected out, and evaluated for histomorphological changes.
Results: The administration of CCl4 increased AST, ALT, ALP, TB, and MDA in serum but it decreased TP , and ALB compared with normal control. Treatment with O. persica extract at three doses resulted in decreased enzyme markers, bilirubin levels, and lipid peroxidation marker (MDA) and increased TP and ALB compared with CCl4 group. The results of pathological study also support the hepatoprotective effects which were observed at doses of 80 and 120 mg/kg.
Conclusion: The results of the present study indicate that ethanol extract of O. persica may have hepatoprotective effect which is probably due to its antioxidant property.

Keywords

Main Subjects


Aniya Y, Koyama T, Miyagi C, Miyahira M, Inomata C, Kinoshita S, Ichiba T. 2005. Free radical scavenging and hepatoprotective actions of the medicinal herb, Crassocephalum crepidioides from the Okinawa Islands. Biol Pharm Bull, 28:19-23.

Asghari G, Nourallahi H, Havaie SA. 2006. Antimicrobial activity of Otostegia persica Boiss extracts. Res Pharm Sci, 1: 53-58.

Ayatollahi SA, Kobarfard F, Asgarpanah J, Ahmed Z. 2007. Chemical constituents from Otostegia persica. J Chem Soc Pakistan, 29: 61-63.

Ayatollahi SA,  Kobarfard F, Asgarpanah J, Rahmati Roodsari M, Fanai Gh, Iqbal Choudhary M. 2009. Diterpenoids of Otostegia persica (Burm.) Boiss. DARU, 17: 290-293.

Balderas RI, Camacho CMR, Carranza RP, Lozano GHG, Castillo ND, Alvarez M. 2007. Hepatoprotective effect of Leucophyllum frutescens on wistar albino rats intoxicated with carbon tetrachloride. Ann Hepatol, 6: 251-254.

Coşkun O, Kanter M, Armutçu F, Çetin K, Kaybolmaz B, Yazgan O. 2004. Protective effects of quercetin, Aa flavnoid antioxidant, in absolute -induced acut gastric ulcer. Eur J Gen Med, 1: 37-42.

Cullen JM.  2005. Mechanistic Classification of Liver Injury. Toxicolo  Pathol, 33:6–8.

Ebrahimpour MR, Khaksar Z, Noorafshan A. 2009. Antidiabetic effect of Otostegia persica oral extract on streptozotocin-diabetic rats. Res J Biol Sci, 4: 1227-1229.

Ghahraman A. 1996. Color atlas of Iranian flora. Research Institute of Forests and Rangelands Publishing, Tehran.

Hajhashemi V, Rabbani M, Asghari G, Saravi Z. 2004. Effects of Otostegia persica on morphine withdrawal syndrome in mice.  Iran J Pharm Res, 3: 171-175.

Hedayati M, Pouraboli I, Mirtajaddini M. 2011. The effect of methanolic extract of Otostegia persica on serum levels of glucose and liver function enzymes in streptozotocin-induced diabetic male rats. J Rafsanjan Univ Med Sci, 10: 84-93.

Hedayati M, Pouraboli I, Pouraboli B. 2010. Effect of methanolic extract of Otostegia persica on serum levels of glucose and lipids in type I diabetic male rats. Iran J Endocrinol Metab, 12: 435-442.

Hedayati M, Pouraboli I, Pouraboli B, Dabiri SH, Javadi A. 2012. Effect of Otostegia persica extract on serum level of glucose and morphology of pancreas in diabetic rats. Koomesh, 13: 201-208.

Hedge IC. 1986. Labiatae of South-west Asia: diversity, distribution and endemism. Proceedings of the Royal Society of Edinburgh. Section B.  Biol Sci, 89: 23-35.

Houzi D, Lekehal M, Moreau A, Moulis C, Feldmann G, Robin MA, Letteron P, Fau D, Pessayre MD. 2000. Cytochrome P450–generated reactive metabolites cause mitochondrial permeability transition, caspase activation, and apoptosis in rat hepatocytes. Hepatol, 32: 303-311.

Hoyland DV, Taylor AJ. 1991. A review of the methodology of the 2-thiobarbituric acid test. Food Chem, 40: 271-291.

Hui ML, Hsien CT, Chau W, Jin L, Chia L, Fen PC. 2008. Hepatoprotective effects of Solanum nigrum Linn extract against CCl4-induced oxidative damage in rats. Chem-Biol Interact, 171: 283-293.

Joshi UJ, Gadge AS, D’Mello P, Sinha R, Srivastava S,  Govil G. 2011. Anti-inflammatory, antioxidant and anticancer activity of Quercetin and its analogues. Int J Res in Pharma and Biomed Sci,  2: 1756-1766.

Lee HS, Jung KH, Hong SW, Park IS, Lee C, Han HK, Lee DH, Hong SS. 2008. Morin protects acute liver damage by carbon tetrachloride (CCl4) in rat.  Arch Pharm Res, 31: 1160-1165.

Leopoldini M, Russo N, Chiodo S, Toscano M. 2006. Iron Chelation by the Powerful Antioxidant Flavonoid Quercetin. J Agric Food Chem, 54: 6343-6351.

Liu H, Zhang L, Lu S. 2012. Evaluation of Antioxidant and Immunity Activities of Quercetin in Isoproterenol-Treated Rats. Molecules, 17: 4281-4291

Luper SND. 1998. A review of plants used in the treatment of liver disease: part 1. Altern Med Rev, 3: 410-421.

Lutz WD, Meinrad B, Andrease S. 2003. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol, 33: 105-136.

McCay PB, Lai EK, Poyer JL, DuBose CM,Janzen EG. 1984. Oxygen- and Carbon-centered Free Radical Formation during Carbon Tetrachloride Metabolism "Observation of  lipid radicals in vivo and in vitro".   J Biol Chem, 259: 2135-2143,

Naghibi F, Mosaddegh M,  Motamed SM,  Ghorbani A.  2005.  Labiatae Family in folk Medicine in Iran: from Ethnobotany to Pharmacology. Iran J Pharm Res, 2: 63-79

Nasiri Bezenjani S, Pouraboli I, Malekpour Afshar R, Mohammadi Gh. 2012.  Hepatoprotective Effect of Otostegia persica Boiss. Shoot Extract on Carbon Tetrachloride-Induced Acute Liver Damage in Rats.  Iran J Pharm Res,  11: 1235-1241

Neetu S, Sangeeta S. 2011. Hepatoprotective potential of aqueous extract of Butea monosperma against CCl4 induced damage in rats. Exp Toxicol Pathol, 63: 671-676.

Nicotera P, Bellomo G, Orrenius S. 1992. Calcium-mediated mechanisms in chemically induced cell death. Annu Rev Pharmacol, 32: 449-470.

OECD, 2001. OECD Guidelines for Testing of Chemicals. No 423:  Acute Oral Toxicity-fixed Dose Method. Organisation for Economic Co-operation and Development, Paris.

Omolola AA, Ebenezer OF. 2010. Hepatoprotective effects of Vernonia amygdalina (astereaceae) in rats treated with carbon tetrachloride. Exp Toxicol Pathol, 62: 197-206.

Pramod K, Deval Rao G, Lakshmayya S, Ramachandra SS. 2008. Antioxidant and hepatoprotective activity of tubers of Momordica tuberosa Cogn. against CCl4 induced liver injury in rats. Indian J Exp Biol, 46: 510-513.

Recknagel RO. 1983. Carbon tetrachloride hepatotoxicity: status quo and future prospects. Trends Pharmacol Sci, 4: 129-131.

Recknagel RO, Glende EA, Dolak JA, Waller RL. 1989. Mechanisms of carbon tetrachloride toxicity. Pharmacol Therapeut, 43: 139-154.

Reynolds ES. 1963. Liver parenchymal cell injury I. Initial alterations of the cell following poisoning with carbon tetrachloride. J Cell Biol, 19: 139-157.

Rubinstein D. 1962. Epinephrine release and liver glycogen levels after carbon tetrachloride administration. Am J Physiol, 203: 1033-1037.

Sadeghi H, Yazdanparast R. 2003.  Effect of Dendrostellera lessertii on the intracellular alkaline phosphatase activity of four human cancer cell lines. J Ethnopharmacol,  86:  11–14

Sadeghi H, Nikbakht  M, Ghaitasi I, Sabzali S. 2008. Hepatoprotective effect of Cichorium intybus on CCl4-induced liver damage in rats.  Afr  J Bioch Res, 2: 141–144

Sadeghi Z, Akaberi A,  Valizadeh J. 2014.  Otostegia persica (Lamiaceae): A review on its ethnopharmacology, phytochemistry, and pharmacology. Avicenna J Phytomed, 4: 79-88.

Sheweita SA, El-Gabar MA, Bastawy M. 2001. Carbon tetrachloride changes the activity of cytochrome P450 system in the liver of male rats: role of antioxidants. Toxicol, 169: 83-92.

Shrififar F, Yassa F, Shafiee A. 2003. Antioxidant activity of Otostegia persica (Labiatae) and its constituents. Iran J Pharm Res, 2: 235-239.

Sreedharan V, Venkatachalam, KK, Namasivayam N. 2009. Effect of morin on tissue lipid peroxidation and antioxidant status in 1, 2-dimethylhydrazine induced experimental colon carcinogenesis. Invest New Drugs, 27:21–30

Subash S, Subramanian P. 2009. Morin a flavonoid exerts antioxidant potential in chronic hyperammonemic rats: a biochemical and histopathological study. Mol Cell Biochem,  327: 153–161

Tofighi Z,  Alipour F,  Yassa N,  Hadjiakhoondi A , Hadavinia H, Goodarzy S,  Golestani R. 2009Chemical composition and antioxidant activity of Otostegia persica essential oil from Iran. Int  J Essen Oil Ther, 3: 45-48

Ulican O, Greksak M, Vancova O,  Zlatos L, Galbavy S, Bozek P, Nakano M. 2003. Hepatoprotective effect of Rooibos tea (Aspalathus linearis) on CCl4 –induced liver damage in rats. Physiol Res, 52:  461-466.

Wagner H, Diesel P, Seitz M. 1974. The chemistry and analysis of silymarin from Silybum marianum Gaertn].  Arznei-Forschung, 24: 466-471.

Yassa N, Sharififar F,  Shafiee  A.  2005. Otostegia persica. as a Source of Natural Antioxidants.  Pharm  Biol, 43: 33-38.

Zhang ZF, Liu Y, Lu LY, Luo P. 2014.   Hepatoprotective activity of Gentiana veitchiorum Hemsl. against carbon tetrachloride-induced hepatotoxicity in mice. Chin J Nat Med,12: 0488 - 0494.