• MANOGARAN MANJU Department of Zoology, Annamalai University, Annamalai Nagar, Chidambaram, Tamil Nadu, India.
  • GANESAN JAGASEESAN Department of Zoology, Annamalai University, Annamalai Nagar, Chidambaram, Tamil Nadu, India.


Objective: Mercury (Hg) is a highly dangerous and also one of the harmful heavy metals which induces oxidative stress in the animal body. The present study is planned to examine the possible defensive result of caffeic acid (CA) against mercury chloride (HgCl2)-induced hepatotoxicity in male albino Wistar rats, Rattus norvegicus.

Methods: Sublethal dose of HgCl2 (1.29 mg/kg body weight) was administrated in rats for 15 days through oral dose and the CA was administrated for another 15 days on mercuric-intoxicated rats. After completing the scheduled exposure time, the rats were sacrificed and the whole liver organ was removed immediately from the animal, and it was used to carry out for biochemical and bioenzymological studies to observe.

Results: The level of lipid peroxidation (LPO) content reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the liver tissue. CA is an energetic component in the phenolic propolis extract and also in a wide variety of plants, and a strong antioxidant helps to prevent oxidative damage and to reduce oxidative stress. The antioxidants such as GPx, CAT, and SOD and non-antioxidant GSH were significantly decreased, and also, the LPO level was increased in mercury toxicity rats. The treatment of CA (5 mg/kg body weight) in the liver tissue shows considerable declining in the level of oxidant content and along with an increase in the level of antioxidant properties by the way of improvement in liver tissues. Antioxidant and non-antioxidant enzyme (LOP, GSH, GPx, SOD, and CAT) activities were also significantly decreased to near untreated control level when compared to Hg-treated group. The CA acid alone treatment showed the enhanced antioxidant levels and not any alteration in the levels of biochemical parameters when compared with control.

Conclusion: These observations of the present experimental study clearly explained the detoxify effects and protective effect of CA against HgCl2 toxicity in liver tissue.

Keywords: Mercuric chloride, Hepatotixcity, Caffeic acid, LOP, SOD, CAT, GSH and GPx.


1. Bharathi E, Jagadeesan G, Vijayakumar M. Hepato-ameliorative effect of hesperidin and ellagic acid on mercuric chloride intoxicated rats. Biomed Aging Pathol 2014;4:17-21.
2. Zalups RK. Molecular interactions with mercury in the kidney. Pharmacol Rev 2000;52:113-43.
3. Mahboob M, Mcneil L, Tolliver T, Ogden L. Effects of chromium picolinate on antioxidant enzyme levels in rats. Toxicol Sci 2002;154: 66-32.
4. Divine KK, Ayala-Fierro F, Barber DS, Carter DE. Glutathione, albumin, cysteine, and cys-gly effects on toxicity and accumulation of mercuric chloride in LLC-PK1 cells. J Toxicol Environ Health A 1999;57: 489-505.
5. Clarkson TW. The three modern faces of mercury. Environ Health Perspect 2002;110 Suppl 1:11-23.
6. Chen SY, Huang CY, Yokoi T, Tang CY, Huang SJ, Lee JJ, et al. Synthesis and catalytic activity of amino-functionalized SBA-15 materials with controllable channel lengths and amino loadings. J Mater Chem 2012;22:2233-43.
7. Husveth F. Physiological and Reproductinal Aspects of Animal Production. Hungary: Debreceni Egyetem; 2011.
8. Bartosz G. Druga Twarz Tlenu. Wolne Rodniki w Przyrodzie, Wydawnictwo Naukowe Poland: PWN, Warszawa; 2004.
9. Niki E. Lipid peroxidation: Physiological levels and dual biological effects. Free Radic Biol Med 2009;47:469-84.
10. da Silva Fm, Marques A, Chaveiro A. Reactive oxygen species: A double-edged sword in reproduction. Open Vet Sci J 2010;4:127-33.
11. Esterbauer H, Waeg G, Puhl H, Dieber-Rotheneder M, Tatzber F. Inhibition of LDL oxidation by antioxidants. EXS 1992;62:145.
12. Cheeseman KH, Slater TF. An introduction to free radical biochemistry. Br Med Bull 1993;49:481.
13. Fleck CH, Kretzschel I, Sperschneider T, Apprenroth D. Renal amino acid transport in immature and adult rats during chromate and cisplatinum-induced nephrotoxicity. Amino Acid 2001;20:201-15.
14. Gutierrez LI, Mazzotti NG, Araujo AS, Klipel RB, Fernandes TR, Llesuy SF, et al. Peripheral markers of oxidative stress in chronic mercuric chloride intoxication. Braz J Med Biol Res 2006;39:767-72.
15. Clifford MN. Chlorogenic acids and other cinnamates nature, occurrence and dietary burden. J Sci Food Agric 1999;79:362-72.
16. Silva T, Oliveira C, Borges F. Caffeic acid derivatives, analogs and applications: A patent review (2009-2013). Expert Opin Ther Pat 2014;24: 1257-70.
17. Jiang RW, Lau KM, Hon PM, Mak TC, Woo KS, Fung KP, et al. Chemistry and biological activities of caffeic acid derivatives from Salvia miltiorrhiza. Curr Med Chem 2005;12:237-46.
18. Parlakpinar H, Sahna E, Acet A, Mizrak B, Polat A. Protective effect of caffeic acid phenethyl ester (CAPE) on myocardial ischemia-reperfusion-induced apoptotic cell death. Toxicology 2005;209:1-4.
19. Kitsati N, Fokas D, Ouzouni MD, Mantzaris MD, Barbouti A, Galaris D, et al. Lipophilic caffeic acid derivatives protect cells against H2O2-induced DNA damage by chelating intracellular labile iron. J Agric Food Chem 2012;60:7873-9.
20. Du Q, Hao C, Gou J, Li X, Zou K, He X, et al. Protective effects of p-nitro caffeic acid phenethyl ester on acute myocardial ischemia-reperfusion injury in rats. Exp Ther Med 2016;11:1433-40.
21. Clifford MN. Chlorogenic acids and other cinnamates nature, occurrence, dietary burden, absorption and metabolism. J Sci Food Agric 2000;80:1033-43.
22. Magnani C, Chiari BG, Isaac VL, Corrêa MA, Salgado HR. In vitro safety evaluation of caffeic acid. Athens J Health 2014b;1:1-8.
23. Sato Y, Itagaki S, Kurokawa T, Ogura J, Kobayashi M, Hirano T, et al. In vitro and in vivo antioxidant properties of chlorogenic acid and caffeic acid. Int J Pharm 2011;403:136-8.
24. Niehaus WG Jr., Samuelsson B. Formation of malonaldehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 1968;6:126-30.
25. Beutler E, Kelley BM. The effect of disodium nitrate on RBC glutathione. Experintia 1963;29:97-101.
26. Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 1984;21:130 2.
27. Sinha AK. Colorimetric assay of catalase. Anal Biochem 1972;47: 389 94.
28. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG, et al. Selenium: Biochemical role as a component of glutathione peroxidase. Science 1973;179:588-90.
29. Duncan BD. Duncan’s multiple range tests for correlated and heteroscedastic mean. Biometrics 1957;13:359-64.
30. Velisek J, Stara A, Li ZH, Silovska S, Turek J. Comparison of the effects of four anaesthetics on blood biochemical profiles and oxidative stress biomarkers in rainbow trout. Aquaculture 2011;310:369-75.
31. Grim JM, Simonik EA, Semones MC, Kuhn DE, Crockett EL. The glutathione-dependent system of antioxidant defense is not modulated by temperature acclimation in muscle tissues from striped bass, Morone saxatilis. Comp Biochem Physiol A Mol Integr Physiol 2013;164:383 90.
32. Pacitti D, Wang T, Page MM, Martin SA, Sweetman J, Feldmann J, et al. Characterization of cytosolic glutathione peroxidase and phospholipid-hydroperoxide glutathione peroxidase genes in rainbow trout (Oncorhynchus mykiss) and their modulation by in vitro selenium exposure. Aquat Toxicol 2013;130-131:97-111.
33. Jagadeesan G. Mercury poisoning and its antidotes. Biochem Cell Arch 2004;4:5-60.
34. Ural M?. Chlorpyrifos-induced changes in oxidant/antioxidant status and haematological parameters of Cyprinus carpio carpio: Ameliorative effect of lycopene. Chemosphere 2013;90:2059-64.
35. Krishnamurthy P, Wadhwani, A. Antioxidant Enzymes and Human Health. Antioxidant Enzyme. ???: Open Access Published; 2012.
36. Uzun FG, Kalender Y. Chlorpyrifos induced hepatotoxic and hematologic changes in rats: The role of quercetin and catechin. Food Chem Toxicol 2013;55:549-56.
37. Kalender S, Uzun FG, Demir F, Uzunhisarc?kl? M, Aslanturk A. Mercuric chloride-induced testicular toxicity in rats and the protective role of sodium selenite and Vitamin E. Food Chem Toxicol 2013;55:456 62.
38. Apayd?n FG, Ba? H, Kalender S, Kalender Y. Subacute effects of low dose lead nitrate and mercury chloride exposure on kidney of rats. Environ Toxicol Pharmacol 2016;41:219-24.
39. Samipillai SS, Jagadeesan G. Protective effect of taurine and glutathione against mercury induced toxicity in the liver tissue of rats. Int J Mod Res Rev 2013;1:7-12.
40. Ibrahim AT. Effects of mercury chloride on oxidative stress biomarkers of some tissues of the African catfish Clarias gariepinus (Burchell, 1822). J Vet Sci Technol 2015;6:242.
41. Pillai SS, Jagadeesan G, Ramesh S, Arumugam P. Role of taurine and glutathione treatment on lipid peroxidation and antioxidant defense in mercury induced toxicity in rats. Int J Hum Sci and Tech 2010;1:72-81.
42. Manickam D, Ramamoorthy KP, Kumar MU, Kumar BS, Subramaniam S, Subramaniam S. Antioxidant activity of traditional siddha formulation of CCL4 induced liver fibrosis in rats. Int J Pharm Pharm Sci 2017;9:81-5.
43. Winston GW, Di Giulio RT. Prooxidant and antioxidant mechanisms in aquatic organisms. Aquat Toxicol 1991;19;137-61.
44. Venkatesan RS, Sadiq AM. In-vitro assay of effect of NaMSA on mercuric chloride induced oxidative stress in erythrocytes. Int J Curr Microbiol Appl Sci 2013;2:703-13.
45. Pappas AC, Zoidis E, Surai PF, Zervas G. Selenoproteins and maternal nutrition. Comp Biochem Physiol B Biochem Mol Biol 2008;151: 361 72.
46. Kanbur M, Eraslan G, Silici S. Antioxidant effect of propolis against exposure to propetamphos in rats. Ecotoxicol Environ Saf 2009;72: 909 15.
47. Vijayaprakash S, Langeswaran K, Kumar SG, Revathy R, Balasubramanian MP. Nephro-protective significance of kaempferol on mercuric chloride induced toxicity in wistar albino rats. Biomed Aging Pathol 2013;3:119-24.
48. Celikoglu E, Aslanturk A, Kalender Y. Vitamin E and sodium selenite against mercuric chloride-induced lung toxicity in the rats. Braz Arch Biol Technol 2015;58:587-94.
49. Schafer FQ, Buettner GR. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med 2001;30:1191-212.
50. Daniel JA, Dal S, Jayan N, Devi SA. Protective activity of Asparagus racemosus in methotrexate-induced liver toxicity in wistar rats. Int J Pharm Pharm Sci 2018;11:253-6.
51. Rajkumar JS, Tennyson S. Mercury induced biochemical alterations as oxidative stress in Mugil cephalus in short term toxicity test. Curr World Environ 2013;8:55-9.
52. Dandapat J, Chainy GB, Rao KJ. Dietary Vitamin-E modulates antioxidant defence system in giant freshwater prawn, Macrobrachium rosenbergii. Comp Biochem Physiol C Toxicol Pharmacol 2000;127: 101-15.
53. Deshmukh R, Kaundal M, Bansal V, Samardeep ???. Caffeic acid attenuates oxidative stress, learning and memory deficit in intra-cerebroventricular streptozotocin induced experimental dementia in rats. Biomed Pharmacother 2016;81:56-62.
54. Yang SY, Hong CO, Lee GP, Kim CT, Lee KW. The hepatoprotection of caffeic acid and rosmarinic acid, major compounds of Perilla frutescens, against t-BHP-induced oxidative liver damage. Food Chem Toxicol 2013;55:92-9.
55. Soumya PS, Poornima K, Ravikumar G, Kalaiselvi M, Gomathi D, Uma C. Nephroprotective effect of Aerva lanata against Mercuric chloride induced renal injury in rats. J Pharm Res 2011;4:2474-6.
56. Tiejing LI, Zhang X, Zhao X. Powerful protective effects of gallic acid and tea polyphenols on human hepatocytes injury induced by hydrogen peroxide or carbon tetrachloride in vitro. J Med Plants Res 2010;4: 247 54.
57. Hanza AA. Curcuma longa, Glycyrrhiza glabra and Moringa oleifera ameliorate diclofenac-induced hepatotoxicity in rats. Am J Pharm Toxicol 2007;2:80-8.
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How to Cite
MANOGARAN MANJU, and GANESAN JAGASEESAN. “IN VIVO HEPATOPROTECTIVE EFFECT OF CAFFEIC ACID ON MERCURIC CHLORIDE-INDUCED BIOCHEMICAL CHANGES IN ALBINO WISTAR RATS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 12, no. 4, Feb. 2019, pp. 119-24, doi:10.22159/ajpcr.2019.v12i4.31609.
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