Preventive and curative effects of Acalypha indica on acetaminophen-induced hepatotoxicity
DOI:
https://doi.org/10.22377/ijgp.v5i1.174Abstract
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
Downloads
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.