IN VIVO AMELIORATIVE POTENTIAL OF CAFFEIC ACID AGAINST HEPATOTOXICITY AND NEPHROTOXICITY INDUCED BY MERCURIC CHLORIDE IN ALBINO WISTAR RATS

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

Abstract

Objective: The current experimental study is designed to scrutinize the possible defensive effect of caffeic acid (CA) against mercury-induced hepatotoxicity in male rats.


Methods: During the treatment periods, a sub-lethal dose of HgCl2 (1.29 mg/kg body weight) was given to rats for 15 days through oral administration and the CA was administrated for 15 days, on mercuric intoxicated rats were observed. After completing the programmed period of experimental work, the blood was drawn through a micro glass tube in the ocular region and separated the serum by centrifuge.


Results: The subsequent serum enzymes were analyzed as the alkaline phosphatase (ALP), alanine transferase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH). Further, the bilirubin, albumin, total cholesterol, urea, and creatinine levels were also noticed in the blood serum of both normal and treated rats. CA is one of the well-known phenolic compounds, and a strong antioxidant helps to prevent oxidative damage and reducing oxidative stress. The biological action of liver biomarker enzymes such as ALT, AST, ALP, and LDH was significantly enhanced and at the same time the drastic increased in the level of albumin was all together decreased. The level of bilirubin, total cholesterol, urea, and creatinine was significantly increased in HgCl2 intoxicated rats. When the treatment of CA on mercury intoxicated rats for 15 days (5 mg/kg body weight), in the serum enzymes (ALT, AST, ALP, and LDH) also declined to near normal level. The level of bilirubin, total cholesterol, urea, and creatinine activities was also significantly declined to near normal level when compared to mercury-treated group. The level of albumin was significantly enhanced. The CA alone treatment showed the enhanced antioxidant levels and not any alteration in the levels of biochemical parameters when compared to control.


Conclusion: These observations of the present experimental work demonstrated the detoxify effects and defensive effect of CA against HgCl2 toxicity in liver tissue.

Keywords: ALT, AST, ALP, LDH, bilirubin, albumin, total cholesterol, urea and creatinine, Mercuric chloride, Caffeic acid

References

1. Durak D, Kalender S, Uzun FG, Demvr F, Kalender Y. Mercury chloride-induced oxidative stress in human erythrocytes and the effect of Vitamins C and E in vitro. Afr J Biotechnol 2010;9:488-95.
2. 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.
3. García-Niño WR, Pedraza-Chaverrí J. Protective effect of curcumin against heavy metals-induced liver damage. Food Chem Toxicol 2014;69:182-201.
4. World Health Organization (WHO). Inorganic mercury. In: Environmental Health Criteria. Vol. 118. Geneva: World Health Organization; 1991. p. 1-115.
5. Bharathi E, Jagadeesan G. Antioxidant potential of hesperidin and ellagic acid on renal toxicity induced by mercuric chloride in rats. Biomed Prev Nutr 2014;4:131-6.
6. Jagadeesan G, Margarat A. Amiliorative action of different solvent extractions of Tribulus terrestris (Linn.) extract on blood transaminese activities of mercuric chloride poisoned mice, Mus musculus. J Ecobiotech 2010;2:53-8.
7. Drasch G, Bose O, Reilly S, Beinhoff C, Roider G, Maydl S. The Mt. Diwata study on the Philippines 1999 assessing mercury intoxication of the population by small scale gold mining. Sci Total Environ 2001;267:151-8.
8. Järup L. Hazards of heavy metal contamination. Br Med Bull 2003;68:167-82.
9. Parsai A, Eidi M, Sadeghipour A. Hepatoprotective effect of sage (Salvia officinalis L.) Leaves hydro-methanolic extract against Aspergillus parasiticus aflatoxin-induced liver damage in male rats. Bull Pharm Res 2014;4:129-32.
10. Schmidt E, Schmidt FW. Aspekte der enzym-diagnostik. Med Welt 1970;21:805-16.
11. Frederiks WM, Vogels IM, Fronik GM. Plasma ornithine carbamyl transferase level as an indicator of ischaemic injury of rat liver. Cell Biochem Funct 1984;2:217-20.
12. Reuben A. Hy’s law. Hepatology 2004;39:574-8.
13. Johansson LE, Lindblad CA, Rastam LL, Ridderstr?ale M. Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity. Eur J Endocrinol 2008;159:577-83.
14. Ingawale DK, Mandlik SK, Naik SR. Models of hepatotoxicity and the underlying cellular, biochemical and immunological mechanism(s): A critical discussion. Environ Toxicol Pharmacol 2014;37:118-33.
15. Weston CJ, Shepherd EL, Claridge LC, Rantakari P, Curbishley SM, Tomlinson JW, et al. Vascular adhesion protein-1 promotes liver inflammation and drives hepatic fibrosis. J Clin Invest 2015;125:501 20.
16. Contreras-Zentella ML, Hernández-Muñoz R. Is liver enzyme release really associated with cell necrosis induced by oxidant stress? Oxid Med Cell Longev 2016;2016:3529149.
17. Vijayakumar M, Jagadeesan G, Bharathi E. Ameliorative potential of ferulic acid on cardiotoxixity induced by mercuric chloride. Bio Prev Nutr 2014;4:239-43.
18. Attri S, Rana SV, Vaiphei K, Sodhi CP, Katyal R, Nain RC, et al. Isoniazid-and rifampicin-induced oxidative hepatic injury—protection by N-acetylcysteine. Hum Exp Toxicol 2000;19:517-22.
19. Sadanobu S, Watanabe M, Nakamura C, Tezuka M. In vitro tests of 1,3-dithia-2-thioxo-cyclopent-4-ene to evaluate the mechanisms of its hepatoprotective action. J Toxicol Sci 1999;24:375-81.
20. Lim HK, Kim HS, Choi HS, Oh S, Jang CG, Choi J, et al. Effects of acetylbergenin against D-galactosamine-induced hepatotoxicity in rats. Pharmacol Res 2000;42:471-4.
21. King EJ, Armstrong AR. Calcium, phosphorus and phosphatases. In: Practical Clinical Biochemistry. New Delhi: CBS Publishers; 1988. p. 458.
22. King J. The dehydrogenases or oxido reductase-lactate dehydrogenase. In: Practical Clinical Enzymology. London: Van D. Nostrand Co. Ltd.; 1965. p. 83-93.
23. Reinhold JG. Manual determination of serum total protein albumin and globulin fractions by buiret method. In: Reiner M, editor. Standard Method of Clinical Chemistry. New York: Academic Press; 1953. p. 88.
24. Malloy HT, Evelyn KA. The determination of bilirubin with the photoelectric colorimeter. J Biol Chem 1937;119:481-90.
25. Allain S, Poon CC, Chan LS, Richmond W. Enzymatic determination of total serum chlosterol. Clin Chem 1974;20:470-5.
26. Fawcett JK, Scott JE. A rapid and pricise method for the determination of urea. J Clin Pathol 1960;13:156-9.
27. Bonsnes RW, Taussky HN. On the calorimetric determination of creatinine by the Jaffe reaction. J Biol Chem 1945;158:851-91.
28. Duncan BD. Duncan’s multiple range tests for correlated and heteroscedastic mean. Biometrics 1957;13:359-64.
29. Batt AM, Ferrari L. Manifestations of chemically induced liver damage. Clin Chem 1995;41:1882-7.
30. Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS, Seeff LB, et al. Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests. Clin Chem 2000;46:2027-49.
31. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: A guide for clinicians. CMAJ 2005;172:367-79.
32. El-Khayat Z, Ahmed RE, Mahmoud SA, Wafaa IR, Tahany RE. Potential effects of bee honey and propolis against the toxicity of ochratoxin A in rats. Maced J Med Sci 2009;2:311-8.
33. Stojevi? Z, Piršljin J, Milinkovi?-Tur S, Zdelar-Tuk M, Ljubi? BB. Activitie activities of AST, ALT and GGT in clinically healthy dairy cows during lactation and in the dry period. Vet Arhiv 2005;75:67-73.
34. ?amanc H, Danijela K, Stoji? V, Dragica S, Vujanac I, Prodanovi? R, et al. Application of the metabolic profile in the prediction and diagnosis of fatty liver in holstein cows. Acta Vet Beograd 2011;61:543-53.
35. Felig P. The glucose-alanine cycle. Metabolism 1973;22:179-207.
36. Kim WR, Flamm SL, Di Bisceglie AM, Bodenheimer HC, Public Policy Committee of the American Association for the Study of Liver Disease. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology 2008;47:1363-70.
37. Anderson FH, Zeng L, Roch NR, Yoshida EM. An assessment of clinical utility of serum ALT and AST in chronic hepatitis C. Hepatol Res 2000;18:63-71.
38. Puoti C, Bellis LB, Martellino F, Guarisco R, Dell-Unto O, Durola L, et al. Chronic hepatitis C and normal ALT levels: Treat the disease not the test. J Hepatol 2005;43:534-5.
39. Lai M, Hyatt BJ, Nasser I, Cyrry M, Fdhal NH. The clinical significant of persistently normal ALT in chronic hepatists B infection. J Hepatol 2007;47:760-7.
40. Kaplwitz N. Mechanism of liver injury. J Hepatol 2000;32:39-47.
41. Rana SV, Singh R, Verma S. Protective effects of few antioxidants on liver function in rats treated with cadmium and mercury. Indian J Exp Biol 1996;34:177-9.
42. Konan NA, Bacchi EM, Lincopan N, Varela SD, Varanda EA. Acute, subacute toxicity and genotoxic effect of a hydroethanolic extract of the cashew (Anacardium occidentale L.). J Ethnopharmacol 2007;110:30 8.
43. Madkour FF, Khalil WF, Dessouki AA. Protective effect of ethanol extract of Sargassum dentifolium (Phaeophyceae) in carbon tetrachloride-induced hepatitis in rats. Int J Pharm Pharm Sci 2012;4:637-41.
44. Rankin SA, Christiansen A, Lee W, Banavara DS, Lopez-Hernandez A. Invited review: The application of alkaline phosphatase assays for the validation of milk product pasteurization. J Dairy Sci 2010;93:5538-51.
45. Pillai SS, Jagadeesan G. Influence of taurine on phosphatases acitivity in selected tissues of mercuric chloride into xicagted mice. J Exp Zool India 2005;8:295-300.
46. Beaussier M, Wendum D, Schiffer E, Dumont S, Rey C, Lienhart A, et al. Prominent contribution of portal mesenchymal cells to liver fibrosis in ischemic and obstructive cholestatic injuries. Lab Invest 2007;87:292-303.
47. Lorenzen PC, Martin D, Clawin-Rädecker I, Barth K, Knappstein K. Activities of alkaline phosphatase, ?-glutamyltransferase and lactoperoxidase in cow, sheep and goat’s milk in relation to heat treatment. Small Rumin Res 2010;89:18-23.
48. Arika WM, Nyamai DW, Osano KO, Ngugi MP, Njagi EN. Biochemical markers of in vivo hepatotoxicity. J Clin Toxicol 2016;6:297.
49. Ramadan A, Soliman G, Mahmoud SS, Nofal SM, Abdel-Rahman RF. Hepatoprotective and hepatotheraputic effects of propolis against D-galactosamine/lipopolysaccharride-induced liver damage in rats. Int J Pharm Pharm Sci 2015;7:372-8.
50. Holman RR, Paul SK, Bethel MA, Neil HA, Matthews DR. Longterm follow-up after tight control of blood pressure in Type 2 diabetes. N Engl J Med 2008;359:1565-76.
51. Joseph J, Mazza MD. Manual of Clinical Hematology. 3rd ed. USA: Lippincott Williams and Wilkins; 2002. p. 461.
52. Bishop MJ, Everse J, Kaplan NO. Identification of lactate dehydrogenase isoenzymes by rapid kinetics. Proc Natl Acad Sci U S A 1972;69:1761 5.
53. Shahsavani D, Mohri M, Gholipour Kanani H. Determination of normal values of some blood serum enzymes in Acipenser stellatus Pallas. Fish Physiol Biochem 2010;36:39-43.
54. Anane R, Creppy EE. Lipid peroxidation as pathway of aluminium cytotoxicity in human skin fibroblast cultures: Prevention by superoxide dismutase+catalase and Vitamins E and C. Hum Exp Toxicol 2001;20:477-81.
55. Bhatti GK, Sidhu IP, Saini NK, Puar SK, Singh G, Bhatti JS. Ameliorative role of melatonin against cypermethrin induced hepatotoxicity and impaired antioxidant defense system in Wistar rats. IOSR J Environ Sci Toxicol Food Technol 2014;8:39-48.
56. Suzuki KT, Kanno S, Misawa S, Aoki Y. Copper metabolism leading to and following acute hepatitis in LEC rats. Toxicology 1995;97:81-92.
57. Turkez H, Geyikoglu F, Colak S. The protective effect of boric acid on aluminum-induced hepatotoxicity and genotoxicity in rats. Turk J Biol 2011;35:293-301.
58. Lindell SL, Hansen T, Rankin M, Danielewicz R, Belzer FO, Southard JH, et al. Donor nutritional status-a determinant of liver preservation injury. Transplantation 1996;61:239-47.
59. Vasudevan D, Sreekumari S, Vaidyanathan K, editors. Clinical enzymology and biomarkers. In: Textbook of Biochemistry. 6th ed. New Delhi: Jaypee Brothers; 2011. p. 146-59.
60. Girish SA, Sudhir A, Avinash WG, Dorle K. Evaluation of hepatoprotective effect of amalkadi ghrita against carbon tetra chloride induced hepatic damage in rats. J Ethanopharmacol 2004;90:229-32.
61. Margarat A, Jagadeesan G. In vivo Recovery of Some Oxidative Parameters (SDH and LDH Activities) in Mercury Intoxicated Mice, Mus musculus. Madras: Proceeding, Environment and Bioethics LIFE, Loyola College; 2000. p. 280-9.
62. Rajamanikandan S, Sindhu T, Durgapriya D, Sophia D, Ragavendran P, Gopalakrishnan VK, et al. Protective effect of Mollugo nudicaulis Lam. On acute liver injury induced by perchloroethylene in experimental rats. Asian Pac J Trop Med 2012;5:862-7.
63. Limdi JK, Hyde GM. Evaluation of abnormal liver function tests. Postgrad Med J 2003;79:307-12.
64. Fevery J. Bilirubin in clinical practice: A review. Liver Int 2008;28:592 605.
65. Singh A, Bhat TK, Sharma OP. Clinical biochemistry of hepatotoxicity. J Clin Toxicol 2011;S4:1.
66. Xiang GH, Tong SL, Liu HZ. Study of interaction of mercuric chloride with bovine serum albumin by multi-spectroscopic method. J Fluoresc 2007;17:512.
67. Silva PR, Neto OC, Laurentiz AC, Junqueira OM, Fagliari JJ. Blood serum components and serum protein test of hybro-pg broilers of different ages. Rev Bras Ciên Avícola Camp 2007;9:229-32.
68. Ajiboye TO. Standardized extract of Vitex doniana sweet stalls protein oxidation, lipid peroxidation and DNA fragmention in acetaminopheninduced hepatotoxicity. J Ethnopharmacol 2015;164:273-82.
69. Dietschy JM, Turley SD, Spady DK. Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans. J Lipid Res 1993;34:1637-59.
70. Peretti N, Marcil V, Drouin E, Levy E. Mechanisms of lipid malabsorption in cystic fibrosis: The impact of essential fatty acids deficiency. Nutr Metab (Lond) 2005;2:11.
71. Grundy SM, Denke MA. Dietary influences on serum lipids and lipoproteins. J Lipid Res 1990;31:1149-72.
72. Renugadevi J, Prabu SM. Naringenin protects against cadmium-induced oxidative renal dysfunction in rats. Toxicology 2009;256:128 34.
73. 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.
74. Vanithasri V, Jagadeesan G. Restoration of antioxidant activity by N-acetylcysteine and gallic acid on kidney tissue of mercuric chloride intoxicated Wistar rats. Int J Biol Pharm Res 2013a;4:302-7.
75. Agarwal R, Goel SK, Behari JR. Detoxification and antioxidant effects of curcumin in rats experimentally exposed to mercury. J Appl Toxicol 2010a;30:457-68.
76. Haibo Y, Zhaofa X, Wei L, Yu D, Bin X. The protective role of procyanidins and lycopene against mercuric chloride renal damage in rats. Biomed Environ Sci 2011;24:550-9.
77. Pal M, Ghosh M. Studies on comparative efficacy of a-linolenic acid and aeleostearic acid on prevention of organic mercury-induced oxidative stress in kidney and liver rat. Food Chem Toxicol 2012;50:1066-72.
78. Al-Attar AM, Al-Taisan WA. Preventive effects of black seed (Nigella sativa) extract on Sprague dawley rats exposed to diazinon. Aust J Basic Appl Sci 2010;4:957-68.
79. Rumbeiha WK, Fitzgerald SD, Braselton WE, Roth RA, Kaneene JB. Potentiation of mercury-induced nephrotoxicity by endotoxin in the Sprague-dawley rat. Toxicology 2000;149:75-87.
80. Wang J, Yang Z, Lin L, Zhao Z, Liu Z, Liu X, et al. Protective effect of naringenin against lead-induced oxidative stress in rats. Biol Trace Elem Res 2012;146:354-9.
81. 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.
82. Arhoghro EM, Ekpo KE, Anosike EO, Ibeh GO. Effect of aqueous extract of bitter leaf (Vernonia amygdalina Del) on carbon tetrachloride (CCl4) induced liver damage in albino Wistar rats. Eur J Sci Res 2009;26:122-30.
83. Swarnalatha L, Reddy PN. Hepatoprotective activity of Sphaeranthus amaranthoides on D-galactosamine induced hepatitis in albino rats. Asian Pac J Trop Biomed 2012;2:S1900-5.
84. Kumar V, Modi PK, Saxena KK. Exploration of hepatoprotective activity of aqueous extract of Tinospora cordifolia an experimental study. Asian J Pharm Clin Res 2013;6:87-91.
85. Jain A, Jain IP, Singh SP, Agarwal A. To evaluate hepatoprotective activity of roots of Cynodon dactylon an experimental study. Asian J Pharm Clin Res 2013;6:109-12.
86. Jyothi B, Lakshmi SM, Anitha K. Protective effect of Mirabilis jalapa Leaves on antitubercular drugs induced hepatotoxicity. Asian J Pharm Clin Res 2013;6:221-4.
87. Pillai SS, Jagadeesan G. Protective role of taurine on mercuric chloride induced neurotoxicity in rats. Poll Res 2006;25:353-6.
88. Navarro CM, Montilla PM, Martin A, Jimney J, Utrilla PM. Free radicals scavenger and anti hepatotoxic activity of Rosmarinus. Planta Med 1993;59:312-4.
89. Pari L, Prasath A. Efficacy of caffeic acid in preventing nickel induced oxidative damage in liver of rats. Chem Biol Interact 2008;173:77-83.
Statistics
91 Views | 85 Downloads
How to Cite
MANJU, M., and GANESAN JAGADEESAN. “IN VIVO AMELIORATIVE POTENTIAL OF CAFFEIC ACID AGAINST HEPATOTOXICITY AND NEPHROTOXICITY INDUCED BY MERCURIC CHLORIDE IN ALBINO WISTAR RATS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 12, no. 4, Feb. 2019, pp. 77-83, https://innovareacademics.in/journals/index.php/ajpcr/article/view/31142.
Section
Original Article(s)