Effect of Cadmium on the Liver and Amelioration by Aqueous Extracts of Fenugreek Seeds, Rosemary, and Cinnamon in Guinea pigs: Histological and Biochemical Study
Cell Biology
Volume 2, Issue 2, March 2014, Pages: 7-17
Received: May 31, 2014; Accepted: Jun. 13, 2014; Published: Jun. 30, 2014
Views 3432      Downloads 298
Mohamed Omer Albasha, Department of Zoology, Alejelat Faculty of Science, Zawia University, Libya
Azab El-Saied Azab, Department of Zoology, Alejelat Faculty of Science, Zawia University, Libya
Article Tools
Follow on us
Hepatotoxic agents can react with the basic cellular components and consequently induce almost all types of liver lesions. Objective: The present work aimed to evaluate effectiveness of fenugreek seeds, rosemary and cinnamon against cadmium induced hepatotoxicity in guinea pigs from the histological and biochemical aspects. Materials and methods: 48 guinea pigs were used for this study and divided into 8 groups. The first 4 groups were control groups, the 5th group was the experimental and administered oral cadmium chloride at a dose of 5 mg/kg. body weight./day for 28 days, the 6th, 7th, and 8th groups co-administered cadmium with aqueous extracts of fenugreek seeds, rosemary and cinnamon at a dose of 150 mg, 220 mg, and 200 mg/ kg body weight /day, respectively. The livers were dissected out, weighted and specimens were taken and processed for light microscopic examinations. Blood samples were obtained for assessment of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ- glutamyltransferase activities, and serum total and direct bilirubin. Results: In cadmium treated animals, there were severe structural damage in the liver. Most of hepatocytes appeared fused together forming eosinophilic syncytial masses. The hepatocytes appeared irregularly arranged with disorganization of hepatic architecture. The hepatocytes appeared large with light and foamy cytoplasm filled with numerous vacuole-like spaces. The nuclei appeared with pyknotic nuclei. The central vein appeared dilated and congested with massive hemorrhage extending to the nearby cells. Mild periductal fibrosis around bile duct in the portal area were observed. Also, there were focal degenerative and necrotic changes along with inflammatory cell infiltration. Decrease in body weight and increase in liver weight were observed. Biochemically, the serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase), and γ- glutamyltransferase activities, serum total and direct bilirubin were elevated. Co-adminstration of fenugreek, rosemary and cinnamon significantly improved the structural changes in the liver and also all the above mentioned biochemical parameters were significantly declined. Conclusion: It can be concluded that, the cadmium had adverse effects on the liver. Aqueous extracts of different natural materials as Fenugreek, rosemary and cinnamon were able to attenuate these effects. So, the populations of high risk to cadmium should be advised to take one of these materials.
Cadmium, Hepatotoxicity, Serum Enzymes Activities (ALT, AST, ALP, γ-GT), Serum Bilirubin, Histology, Fenugreek Seeds, Rosemary, Cinnamon
To cite this article
Mohamed Omer Albasha, Azab El-Saied Azab, Effect of Cadmium on the Liver and Amelioration by Aqueous Extracts of Fenugreek Seeds, Rosemary, and Cinnamon in Guinea pigs: Histological and Biochemical Study, Cell Biology. Vol. 2, No. 2, 2014, pp. 7-17. doi: 10.11648/j.cb.20140202.11
Grattagliano I, Bonfrate L, Catia VD, Wang HH, Wang DQH and Portincasa P: Biochemical me-chanisms in drug-induced liver injury. World J Gastroenterol 2009;5: 4865-4876
World Health Organization (WHO): Cadmium: Air Quality Guidelines, 2nd ed., World Health Organization, Copenhagen, Denmark, 2000
Jarup L: Hazards of heavy metal contamination. Br Med Bull 2003; 68: 167-182
Renugadevi J and Prabu, SM: Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin. Exp Toxicol Pathol 2010;62: 171-181
Heeba GH, and Abd-Elghany MI: Effect of combined administration of ginger (Zingiber officinale roscoe) and otorvastatin on the liver of rats. Phytomedicine 2010;17:1076-1081
Ho C, Ferrara T, Chin Q, Rosen R and Huang M: Phytochemicals in teas and rosemary and their cancer preventive properties in: food phytochemicals for cancer prevention. American Chemical Society, Washington, DC, 1994, pp.2-19
Flammang AM, Cifone MA, Ereson GL and Stankowskci LF: Genotoxicity testing of fenugreek extract. J Food Chem Toxicol 2004;42: 205-208
Basch E, Ulbricht C, Kuo G, Szapary P and Smith M: Therapeutic application of fenugreek. Altern Med Rev 2003; 8(1): 20-27
Aruoma O, Halliwell B, Aeschbach R, Loligers J: Antioxidant and pro-oxidant properties of active rosemary constituents: carnosol and carnosic acid. Xenobiotica 1992;22: 257-268
Moselhy SS and Ali HKH: Hepatoprotective effect of Cinnamon extracts against carbon tetra-chloride induced oxidative stress and liver injury in rats. Biol Res 2009;42: 93-98
Eidi A, Mortazavi P, Bazargan M, and Zaringhalam J: Hepatoprotective activity of cinnamon ethanolic extract against CCl4 -induced liver injury in rats. Excli J 2012;11:495-507.
Kassim, H M: Effect of fenugreek seeds extract on liver cells and en-zymes of male albino mice. Iraqi J Sci 2012;53(1): 62-67
Amin A and Hamza AA: Hepato-protective effects of hibiscus, rosemarinus and salvia on azathioprine-induced toxicity in rats. Life Sci J 2005;77: 266-278
Hasanein MA, Abdel Gawad SH and Abd El-Megeid AA: Effect of water extract prepared from green tea, black tea and cinnamon on obese rats suffering from di-abetes.World Appl Sci J 2012; 20(7): 976-987
Rajasekaran A and Periasamy M : Hepato-protective effect of ethanolic leaf extract of Calycopteris floribunda L on cadmium induced hepa-totoxicity in rats. Res J Pharmacol Biol Chem Sci 2012;3(3): 382-390
Dorman HJ, Peltoke-to , Hiltunen R and Tikkanen MJ: Characterization of the antioxidants properties of de-odourised aqueous extracts from selected lamiaceae herbs. Food Chem 2003;83: 255-262
Sakr SA and Lamfon HA: Protective effect of rosemary (Rosmarinus officinalis) leaves extracts on carbon tetrachloride-induced nephrotoxicity in albino rats. Life Sci J 2012;9(1): 779-785
Flecknell PA: Laboratory Animal Anaesthesia. An Introduction for research workers and technicians. Aca-demic Press, New York, 1996
Ross MH, Reith EJ and Romrell LJ: Histology, A Text Atlas (2nd ed.) Baltimore. Williams &Wilkins ,1989, pp.51- 84
Reitman S, and Frankel A: Colo-rimetric method for determination of serum glutamate oxaloaectate and glutamic pyruvate transaminase. Amer J Clin Pathol 1957; 28: 56-58
Kind PRN, King EJ, Varley H, Gowenlock AH, Bell M: Method of practical clinical biochemistry. Heinman, London, 1980, pp. 899-900
Dangerfield WG and Finlayson R: Estimation of bilirubin in serum. J Clin Pathol 1953;6(3):173-177
Szas G: Reaction rate method for gamma glutamyl transferase activity in serum. Clin Chem 1976;22: 2031-2055
EL-Sokkary GH, Nafady AA, and Shabash EH: Melatonin administration ameliorates cadmium-induced oxidative stress and morphological changes in the liver of rat. Ecotoxicol Environ Safe 2010;73(3): 456-463
Lakshmi GD, Kumar PR, Bharavi K, Annapurna P, Rajendar B, Patel PT, Kumar CSVS, and Rao GS: Protective ef-fect of Tribulus terrestris L on liver and kidney in cadmium intoxicated rats. Indian J Exper Biol 2012;50: 141-146
Adikwu E, Deo O, and Geoffrey, OBP: Hepatotoxicity of cadmium and roles of mitigating agents. Br J Pharmacol Toxicol, 2013;4(6): 222-231
Zhai Q, Wang G, Zhao J, Liu X, Tian F, Zhang H, Chen W: Protective effects of Lactobacillus plantarum CCFM8610 against acute cadmium toxicity in mice. Appl Environ Micro 2013;79(5): 1508–1515
Mahran AA, Osman HEH, Abd El-Mawla AMA,and Attia AM: Protective effect of zinc (Zn) on the histology and histochemistry of liver and kidney of albino rat treated with cadmium. J Cytol Histol 2011;2 (4): 2-9
Gathwan KH, Al Ameri QMA, Zaidan HK, Al Saadi AH, and Ewadh MJ: Heavy metals induce apoptosis in liver of mice. Inter J Appl Biol Pharmacol Technol 2012; 3(2): 146-150
Robbins SL, and Angell M: Basic Pathology.2nd ed. W.B. Saunders Company, Phildelphia, London, 1976
Muller L : Consequences of cadmium tox-icity in rat hepatocytes: Mitochondrial dysfunction and lipid peroxidation. Toxicol 1986;40: 285-295
Koyu A, Gokcimen A, Ozguner F, Bayram DS, and Kocak A : Evaluation of the ef-fects of cadmium on rat liver. Mol Cell Biochem 2006;284: 81-85
Liu J, Qu W, and Kadiiska MB: Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicol Appl Pharmacol 2009;238: 209-214
Packer, L and Cadenas E: Oxidative Stress and Disease. In: Cadenas, E. and L. Packer (Ed.), Handbook of Antioxidants. 2nd Edn., Marcel Dekker Inc., New York, Basel, USA, 2002, pp. 5-8.
Rikans LE,and Yamano T: Mechanisms of cadmium mediated acute hepatotoxicity. J Biochem Mol Toxicol 2000; 14: 110-117
Waisberg M, Joseph P, Hale B and Beyersmann D: Molecular and cellular mechanisms of cadmium carcinogenesis: a review. Toxicol 2003;192: 95-117
Ahmad F, and Tabassum N: Experimental models used for the study of antihepatotoxic agents. J Acute Disease 2012: 85-89
Pillai A, and Gupta S: Anti-oxidant enzyme activity and lipid peroxidation in liver of female rats co-exposed to lead and cad-mium: Effects of vitamin E and Mn 2+. Free Radic Res 2005;39: 707-712
Jurczuk, M, Brzoska MM, Moniuszko-Jakoniuk J, Galazyn-Sidorczuk M, and Kulikowska-Karpinska E: Antioxi-dant enzymes activity and lipid peroxidation in liver and kidney of rats exposed to cadmium and ethanol. Food Chem Toxicol 2004;42: 429-438
Dudley RE, Svoboda DJ, and Klaassen CD: Time course of cadmium-induced ultrastructural changes in rat liver. Toxicol Appl Pharmacol 1984;76: 150-160
Wong LT, Whitehouse LW, Solemonraj G, and Paul CJ: Pathways of ace-taminophen conjugation in the mouse. Toxicit Lett 1981;9: 145-151
Savides MC, and Oehne FW: Acetaminophen and its toxicity. J App Toxicol 1983;3: 95-111
Bertin G, and Averback D: Cadmium: Cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences. Biochim 2006;8: 2549-1559
Kaplan MM: Primary biliary cirrhosis. N Engl J Med 1987;316(9): 521- 528
Adebajo AC, Iwalewa EO, Obuotor EM, Ibi-kunle GF, Omisore NO, and Adewunmi CO: Pharmacological properties of the extract and some isolated compounds of Clausena lansium stem bark: anti-trichomonal, antidiabetic, an-ti-inflammatory, hepatoprotective and antioxidant effects. J Ethnopharmacol 2009;122(1): 10-19
Singh VK, Dixit P, and Saxena PN: Cybil induced hepato-biochemical changes in wistar rats. J Environ Biol 2005;26(4): 725-727
Jaramillo-Jurez F, Rodrguez-Vzquez ML, Rincn-Snchez AR, Consolacin Martnez M, Ortiz GG, and Llamas J: Acute renal failure induced by carbon tetrachloride in rats with hepatic cirrhosis. Ann Hepatol. 2008;7(4): 331-338
Bishop LM, Fody, PE and Schoe, HL: Clinical Chemistry Principles, Procedures Correlations 5th ed. Lippincott Williams and Wilkins, Philadelphia, Hong Kong, 2005, pp.220-253
Naik P: Biochemistry, 3rd ed, Jaypee Publishers Ltd. Panama, 2010, pp.138-141, 565.
Liss G, Greenberg RA, and Tamburro CH: Use of serum bile acids in the identification of vinyl chloride hepatotoxicity. Am J Med 1985;78:68-73
Prabu SM, Selva-rajan N, Hemalatha S,and Kumar RT: Hepatoprotective effect of Andrographis paniculata on cad-mium induced toxicity in male wistar rats. Toxicol Int 2008;15: 21- 25
Prabu MS, Muthu-mani M and Shagirtha K: Protective effect of piper betle leaf extract against cadmium-induced oxidative stress and hepatic dysfunction in rats. Saudi J Biol Sci 2012;19: 229-239
Yamano T , Shimizu M, and Noda T: Comparative effects of repeated administration of cadmium on kidney, spleen, thymus, and bone marrow in 2-, 4-, and 8-month-old male Wistar rats. Toxicol Sci 1998;46: 393-402
Kaltreider RC, Davis AM, Lariviere JP, and Hamilton JW: Arsenic alters the func-tion of the glucocorticoid receptor as a transcription factor. Environ Health Perspect 2001;109: 245-251
Osawa T, and Kato Y: Protective role of antioxidative food factors in oxidative stress caused by hyperglycemia. Ann N Y Acad Sci 2005;1043: 440-451
Botsoglou N, Tait-zoglou I, Zervos I, Botsoglou E, Tsantarliotou M,and Chatzopoulou PS: Potential of long-term die-tary administration of rosemary in improving the antioxidant status of rat tissues following carbon tetrachloride intoxication. Food Chem Toxicol 2010;48: 944-950
Das, S: Hepatoprotective activity of methanol extract of fenugreek seeds on rats. Int J Pharmacol Sci Res 2014;5(4): 1506-1513
Kumar P, and Bhandari U: Protective effect of Trigonella foenum-graecum Linn. on monosodium glutamate-induced dyslipidemia and oxidative stress in rats. Indian J Pharmacol 2013;45:136-140
AL-Shaikh MN: Histological and histochemical changes in diabetic male rat liver and intestine and protective effect of cinnamon oil. J Fac Med Baghdad 2010;52(3): 366-371
Kaviarasan S, Ramamurti N, Gunasekaran P, Varalaksmi E, Anuradha CV: Fenu-greek (Trigonella foenum-graecum) seed extract prevents etanol-induced toxicity and apoptosis in chang liver cells, Alcohol Alcohol 2006;41 (3): 267-273
Hoefler C, Fleurentier J, Mortier F, Pelt J, and Guillemain J: Comparative choleretic and hepatoprotective properties of young sprouts and total plant extracts of Rosemarinus officinalis in rats. J Ethnopharmacol 1987;19: 133 - 143
Sotelo-Felix J, Martinez-Fong D, and Mureil De la Torre, P: Protective effect of car-nosol on CCl4-induced acute liver damage in rats. Europ J Gastroenterol Hepatol 2002;14: 1001-1006
Joyeux M, Roland A, Fleurentin J, Mortier F, and Dorfman P: Tert-Butyl hy-droperoxide induced injury isolated rat hepatocytes: a model for studying anti-hepatotoxoxic crude drugs. Plant Med 1990;56:171-174
Del Bano MJ, Castillo J, Garcia OB, Lorente, J, Martin- Gil R, Acevado C, and Alcaraz M: Radio-protective- antimutagenic effects of rosemary phenolics against chromosomal damage induced in human lymphocytes by gamma-rays. J Agric Food Chem 2006;54(6): 2064-2068
Fahim F, Esmat A, Fadel H and Hassan K: Allied studies on the effect of Rosemarinus officinalis L. on experimental hepatotoxicity and mutagenesis. Inter J Food Sci Nutr 1999;50: 413-427
Lamaison J, Petitjean-Freytet C, and Carnat A: Rosema-rinic acid, total hydroxycinnamic derivatives and antioxidant activity of Apiaceae, Borranginaceae and Lamiceae medicinals. Annal Pharmacol Fran 1990;48: 103-108
Haraguchi H, Saito T, Okamura N, and Yagi, A: Inhibition of lipid peroxidation and superoxide generation by diterpenoids from Rosemarinus officinalis. Plant Med 1995;61: 333-336
Munne-Bosch S, Schwarz K, and Alegre L: Enhanced Formation of alpha-tecopherol and highly oxidized abietane diterpenes in water-stressed rosemary plants. Plant Physiol 1999;121: 1047-1052
Debersac P, Verne-vaut M, Amiot MJ, Suschetet M, and Siess MH: Effect of a water soluble extract of rosemary and its purified component rosemarinic acid on xenobiotic- metabolizing enzymes in rat liver. Food Chem Toxicol 2001;39: 109-117
Shihabudeen MS, Priscilla H, and Thirumurugan K: Cin-namon extract inhibits α-glucosidase activity and dampens postprandial glucose excursion in di-abetic rats. Nutr Metab 2011;8:1-11
Baek NL, Kim YS, Kyung JS,and Park KH: Isolation of anti-hepatotoxic agents from the roots of Astralagus membranaceous. Korean J Pharmacol 1996;27:111-116
Xiong X, Chen W, Cui J, Yi S, Zhang Z, and Li K: Effects of ursolic acid on liver protection and bile secretion. Zhong Yao Cai 2003;26: 578-581
Tran QI, Adnyana IK, Tezuka Y, Nagaoka T, Tran QK,and Kadota S: Triterpene saponins from Vietnamese ginseng (Panax vietnamensis) and their hepatocyte protective activity. J Nat Prod 2001; 64: 456-61
Vijayan P, Prashanth HC, Dhanraj SA, Badami S, and Suresh B: Hepatoprotective effect of total alkaloid fraction of Solanum pseudocapsicum leaves. Pharmaceut Biol 2003;41: 443-448
Tattini M, Galardi C, Pinelli P, Massai R, Remorini D,and Agati G: Differential ac-cumulation of flavonoids and hydroxyl cinnamates in leaves of Ligustrum vulgare under excess light and drought stress. New Phytol 2004;163: 547-561
Gould KS, and Lister C: Flavonoid functions in plants. In: Andersen OM, Markham KR (eds.): Flavonoids: chemistry, biochemistry and applications. London: CRC Press, 2006, pp. 397-440
Heim KE, Tagliaferro AR, and Bobilya DJ: Flavonoid antioxidants: chemistry, metabolism and structure activity relationships. J Nutr Bio-chem 2002;10:572-584
Science Publishing Group
1 Rockefeller Plaza,
10th and 11th Floors,
New York, NY 10020
Tel: (001)347-983-5186