Preventive and curative effects of Acalypha indica on acetaminophen-induced hepatotoxicity

M. Mathew, C. Nair, T. Shenoy, J. Varghese

Abstract


Effect of ethanol extract of the leaves of Acalypha indica (Euphorbiaceae) was investigated against acetaminophen-induced hepatic damage. Acetaminophen (paracetamol) at the rate of 1 g/kg produced liver damage in rats as manifested by the significant (P<0.001) rise in serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), compared to respective control values. Treatment of rats with acetaminophen led to a marked increase in lipid peroxidation as measured by malondialdehyde (MDA). This was associated with a significant reduction in superoxide dismutase (SOD) and glutathione (GSH)
contents. Pretreatment of animals with the plant extract (100 mg/kg) orally once daily for 5 days prevented (P<0.01) the acetaminopheninduced rise in serum transaminases (AST and ALT) and ALP. Post treatment with five successive doses of the extract (100 mg/kg) restricted the hepatic damage induced by the above said Paracetamol (P<0.001). Histological changes around the hepatic central vein were recovered by administration of the drug. Thus, it is evident that these biochemical and histological alterations resulting from acetaminophen administration were inhibited by pre and post treatment with A. indica leaf extract. One notable study of the study was the spontaneous recovery of liver damage within a week after stopping paracetamol. These results indicate that the crude
ethanol extract of A. indica exhibits hepatoprotective action through antioxidant effect and validates the traditional use of the plant in hepatic dysfunction.
Key words: Acalypha indica, acetaminophen, hepatotoxins, transaminases

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References


Mathers CD, Stein C, Ma Fat D, Rao C. Global burden of diseases –

Version 2, methods and results. GPE discussion paper No:50.

Geneva world Health Organization; 2002. p. 1-2.

Salomon JA, Murray CJ. The epidemiological transition revisited:

Compositional models for causes of deaths by age and sex. Popul

Dev Rev 2002;28:205-28.

WHO World Health Report 2002. Reducing risks promoting

healthy life. Geneva: WHO; 2002. p. 1-13.

Mathew M, Shenoy KT, Gopi TV. Hepatoprotective activity of

Acalypha indica: A comparative evaluation. Drug Lines 2002-

;5:5-7.

Anbu Jeba Sunilson J, Anita GK, Jisha J, Varatharajan R, Jayaraj

P, John T. Formulating and screening of herbal wound healing

ointment. Adv Pharmacol Toxicol 2008;2:1-7.

Anbu Jeba Sunilson J, Mathu MS, Syam MM, Anita GK, John T,

Jayaraj P. Antidiabetic activity of Momordica tuberose Roxb COGN

tuber extracts. Int J Pharmacol Biol Sci 2008;9:41-5.

Suma V, Swamy MM, Vijayalakshmi S, Reddy YS, Suresh B.

Pharmacological observations on Sida rhomboidea: A report.

Indian Drugs 1994;31:421-5.

Zimmerman M. Ethical guidelines for investigations of

experimental pain in conscious animals. Pain 1983;16:109-10.

Rao GM, Rao G, Ramanarayanan K, Sreenivasan KK. Effect of

hepatogard on paracetamol induced liver injury in male albino

rats. Indian Drugs 1993;30:40-4.

Bergmeyer HU, Bowers S Jr, Horder M, Moss DW. Provisional

recommendations on IFCC methods for the measurement of

catalytic concentrations of enzymes: Part II. Clin Chem 1977;

:887-99.

Berg HU, Horder M. IFCC method for the measurement of catalytic

concentrations of enzymes: Part -3. IFCC method for alanine amino

transferase. J Clin Chem Clin Biochem 1980;18:521-34.

Bowers GN Jr, McComb RB. Measurement of total alkaline

phosphatase activity in human serum. Clin Chem 1975;21:

-95.

Okhawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal

tissue by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.

Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric

assay for superoxide dismutase. Indian J Biochem Biophys

;21:130-2.

Benke GM, Cheever KL, Mirer FE, Murphy SP. Comparative

toxicity, anticholinesterase action and metabolism of methyl

parathione and parathione in sunfish and mice. Toxicol Appl

Pharmacol 1974;28:97-109.

Kulkarni SK. Hand book of experimental pharmacology. New

Delhi; India. Vallabh Prakashan; 1999. p. 172.

Kiso Y, Tohkin M, Hikino H, Hattori M, Sakamoto T, Namba T.

Mechanism of antihepatotoxic activity of Glycyrrhizin, I: Effect

on free radical generation and lipid peroxidation. Planta Med

;50:298-302.

Robin MW, Racz WJ, McElligott TF. Scanning electron microscopic

examination of Acetaminophen-induced Hepatotoxicity and

congestion in mice. Am J Pathol 1983;113:321-30.

Hong RW, Rounds JD, Helton WS, Robinson MK, Wilmore DW.

Glutamine preserves liver glutathione after lethal hepatic injury.

Ann Surg 1992;215:114-9.

Lee E, Miki Y, Ichi FY, Simizu H, Karia K. Selective release of

Glutathion transferase subunits from primary cultured rat

hepatocytes by carbon tetrachloride and deoxycholic acid.

Toxicology 1991;67:237-48.

Dixon MF, Nimmo J, Prescott LF. Experimental paracetamol -

induced hepatic necrosis: A histopathological study. J Pathol

;103:225-7.

Weishen B, Kamendulis LM, Ray SD, Corcoran GB. Acetaminopheninduced

cytotoxicity in cultured mouse hepatocytes: Correlation

of nuclear Ca2+ accumulation and early DNA fragmentation with

cell death. Toxicol Appl Pharmacol 1991;111:242-54.

Keppler D. Liver morphology and enzyme release: Further studies

in the isolated perfused rat liver. In: Schmidt E, Schmidt FW, Mohr

J, Otto P, Vido I, Wrogeman K, et al, editors. Pathogenesis and

mechanism of liver cell necrosis. 4th ed. Lancester: Medical and

Technical publications; 1975. p. 147.

Koul IB, Kapil A. Effect of diterpenes from Andrographis paniculata

on antioxidant defense system and lipid peroxidation. Indian J

Pharmacol 1994;26:296-300.

Singh B, Saxena AK, Chandran BK, Anand KK, Suri OP, Suri KA,

et al. Hepato protective activity of Verbenalin on experimental liver

damage in rodents. Fitoterapia 1998;69:135-41.

Pauline T, Dipti P, Anju B, Kavimani S, Sharma SK, Kain AK, et al.

Studies on toxicity, anti stress and hepato-protective properties of

Kombucha tea. Biomed Environ Sci 2001;14:207-13.

Cederbaum AI, Cohen G. Microsomal metabolism of hydroxyl

radical scavenging agents: Relationship to the microsomal

oxidation of alcohol. Arch Biochem Biophys 1980;19:438-47.

Ashbum LL, MeQueency AJ, Faulkner RR. "Scarring and

precirrhosis” of the liver in chronic phosphorus poisoning of

Guinea pig. Proc Soc Exp Biol Med 1948;67:351-8.

Mitchell JR, Zimmerman HJ, Ishak KG, Thorgeirsson UP,

Timbrell JA, Snodgrass WR, et al. Isoniazid liver injury: Clinical

spectrum, pathology and probable pathogenesis. Ann Intern Med

;84:181-92.

Savides MC, Oehme FW. Acetaminophen and its toxicity. J Appl

Toxicol 1983;3:95-111.

Zhou L, Erickson RR, Holtzman JL. Studies comparing the kinetics How to cite this article: ***

of cysteine conjugation and protein binding of paracetamol by

hepatic microsomes from male mice. Biochim Biophys Acta

;1335:153-60.




DOI: http://dx.doi.org/10.22377/ijgp.v5i1.174

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