• MARIAM A KADHEM Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Basra, Basra, Iraq.


Objective: The objective of our study is to investigate the effect of the ethanolic extract of Saussurea lappa against paracetamol-induced hepatorenal toxicity in male rabbits.

Methods: Eighteen male rabbits were used for this study and were divided into three groups of six rabbits each. Group 1: Rabbits were the normal (negative control), Group 2: (Positive control) Rabbits were administered paracetamol at dose 300 mg/kg body weight (B.W) for 14 day, and Group 3: Rabbits received paracetamol at dose 300 mg/kg B.W then treated with ethanolic extract of S. lappa at dose 300 mg/kg B.W for 14 day.

Results: The obtained results showed a significant decrease (p≤0.05) in B.W, red blood cells count, white blood cells count, neutrophil, total protein, and albumin with significant (p≤0.05) increase in lymphocyte, alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and malondialdehyde in rabbits of positive control group, histological studies showed many pathological changes in liver and kidney when compared with negative control group. The oral administration of the ethanolic extract of S. lappa significantly protected the hepatic and kidney cells from damage, the hematological and biochemical parameters were also almost normal in extract treated rabbits compared to the control group.

Conclusion: Our study indicates that the roots of S. lappa act as antioxidant substance and have hepato and renoprotective effect against toxicity induced by paracetamol.

Keywords: Paracetamol, Saussurea lappa extract, Liver, Kidney, Rabbit


1. Sheen CL, Dillon JF, Bateman DN, Simpson KJ, Macdonald TM. Paracetamol toxicity: Epidemiology, prevention and costs to the health-care system. QJM 2002;95:609-19.
2. Jollow DJ, Thorgeirsson SS, Potter WZ, Hashimoto M, Mitchell JR. Acetaminophen-induced hepatic necrosis. VI. Metabolic disposition of toxic and nontoxic doses of acetaminophen. Pharmacology 1974;12:251-71.
3. Mohandas J, Duggin GG, Horvath JS, Tiller DJ. Metabolic oxidation of acetaminophen (para-cetamol) mediated by cytochrome P-450 mixed-function oxidase ad prostaglandin endoperoxidase synthetase in rabbit kidney. Toxicol Appl Pharmacol 1981;61:252-9.
4. Rosen GM, Rauckman EJ, Ellington SP, Dahlin DC, Christie JL, Nelson SD, et al. Reduction and glutathione conjugation reactions of N-acetyl-p-benzoquinone imine and two dimethylated analogues. Mol Pharmacol 1984;25:151-7.
5. Yank V, Rennie D. Disclosure of researcher contributions: A study of original research articles in the lancet. Ann Intern Med 1999;130:661-70.
6. Godlee F, Jefferson T. Peer Review in Health Sciences. London: BMJ Books; 1999.
7. Pitkin RM, Branagan MA, Burmeister LF. Accuracy of data in abstracts of published research articles. JAMA 1999;281:1110-1.
8. Carpenter HM, Mudge GH. Acetaminophen nephrotoxicity: Studies on renal acetylation and deacetylation. J Pharmacol Exp Ther 1981;218:161-7.
9. Jones AF, Vale JA. Paracetamol poisoning and the kidney. J Clin Pharm Ther 1993;18:5-8.
10. Eguia L, Materson BJ. Acetaminophen-related acute renal failure without fulminant liver failure. Pharmacotherapy 1997;17:363-70.
11. Ray SD, Mumaw VR, Raje RR, Fariss MW. Protection of acetaminophen-induced hepatocellular apoptosis and necrosis by cholesteryl hemisuccinate pretreatment. J Pharmacol Exp Ther 1996;279:1470-83.
12. Webster PA, Roberts DW, Benson RW, Kearns GL. Acetaminophen toxicity in children: Diagnostic confirmation using a specific antigenic biomarker. J Clin Pharmacol 1996;36:397-402.
13. Montilla P, Barcos M, Munoz MC, Bujalance I, Munoz-Castaneda JR, Tunez I, et al. Red wine prevents brain oxidative stress and nephropathy in streptozotocin-induced diabetic rats. J Biochem Mol Biol 2005;38:539-44.
14. Mansour HH, Hafez HF, Fahmy NM. Silymarin modulates cisplatin-induced oxidative stress and hepatotoxicity in rats. J Biochem Mol Biol 2006;39:656-61.
15. Shu YZ. Recent natural products based drug development: A pharmaceutical industry perspective. J Nat Prod 1998;61:1053-71.
16. Ravishankar B, Shukla VJ. Indian systems of medicine: A brief profile. Afr J Tradit Complement Altern Med 2007;4:319-37.
17. Kaido TL, Veale DJ, Havlik I, Rama DB. Preliminary screening of plants used in South Africa as traditional herbal remedies during pregnancy and labour. J Ethnopharmacol 1997;55:185-91.
18. Pradeesh S, Swapna TS. In vitro hepatoprotective activity of a wild medicinalplant from Western Ghats Bidens biternata (lour.) Merr and Sheriff. Int J Res Rev Pharm Appl Sci 2015;5:1246-50.
19. Ravinder S, Chahal KK, Nancy S. Chemical composition and pharmacological activities of Saussurea lappa: A review. J Pharmacogn Phytochem 2017;6:1298-308.
20. Barrero AF, Oltra JE, Alvarez M, Raslan DS, Saúde DA, Akssira M, et al. New sources and antifungal activity of sesquiterpene lactones.Fitoterapia 2000;71:60-4.
21. Seki K, Hashimoto A, Kobayashi H, Kawahara Y, Yamahara J. Motility inhibitory effect on anchusan and jintan and its active components in Anisakis type larvae. Yakuri Chiryo 1991;19:3657-66.
22. Upadhyay OP, Singh RH, Dutta SK. Studies on antidiabetic medicinal plants usedin Indian folklore. Sachitra Ayurved 1996;48:949-55.
23. Ko SG, Kim HP, Jin DH, Bae HS, Kim SH, Park CH, et al. Saussurea lappa induces G2-growth arrest and apoptosis in AGS gastric cancer cells. Cancer Lett 2005;220:11-9.
24. Khalid A, Rehman U, Sethi A, Khilji S, Fatima U, Khan MI, et al. Antimicrobial activity analysis of extracts of Acacia modesta, Artimisia absinthium, Nigella sativa and Saussurea lappa against gram positive and gram negative microorganisms. Afr J Biotechnol 2011;10:4574-80.
25. Kulkarni S, Desai S. Immunostimulant activity of inulin isolated from Saussurea lappa roots. Indian J Pharm Sci 2001;63:292-4.
26. Sutar N, Garai R, Sharma US, Singh N, Roy SD. Antiulcerogenic activity of Saussurea lappa root. Int J Pharm Life Sci 2011;2:516-20.
27. Sunkara Y, Robinson A, Suresh B, Naidu K, Vishnuvardhan M, Ramakrishna M, et al. Antiinflammatory and cytotoxic activity of chloroform extractof roots of Saussurea lappa. J Pharm Res 2010;3:1775-8.
28. Yaeesh S, Jamal Q, Shah AJ, Gilani AH. Antihepatotoxic activity of Saussurea lappa extract on D-galactosamine and lipopolysaccharide-induced hepatitis in mice. Phytother Res 2010;24 Suppl 2:S229-32.
29. ItarboneJ B. Phytochemical Methods a Guide to Modern Techniques. Dordrecht: Kluwer Academic Publishers Imprint; 1998.
30. Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957;28:56-63.
31. Peters T Jr. Proposals for standardization of total protein assays. Clin Chem 1968;14:1147-59.
32. Doumas BT, Watson WA, Biggs HG. Albumin standards and the measurement of serum albumin with bromcresol green. Clin Chim Acta 1971;31:87-96.
33. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978;52:302-10.
34. Luna LG. Manual of History Staining Methods of the Armed Forces Institute of Pathology. 3rd ed. New York: Mcgraw Hill Book Co.; 1968.
35. SPSS Statistical Packages for the Social Sciences. Statistical Software for Windows Version 16.0 Microsoft. Chicago, IL, USA: SPSS Statistical Packages for the Social Sciences; 2012.
36. Gonzalez-Casas R, Jones EA, Moreno-Otero R. Spectrum of anemia associated with chronic liver disease. World J Gastroenterol 2009;15:4653-8.
37. Kornberg A, Polliack A. Paracetamol-induced thrombocytopenia and haemolytic anaemia. Lancet 1978;2:1159.
38. Ma L, Liu Z, Zhou B, Yang L, Liu Z. Inhibition of free radicalinduced oxidativehemolysis of red blood cells by green tea polyphenols. Chin Sci Bull 2000;45:2052-6.
39. Pandey RS. Saussurea lappa extract modulates cell mediated and humoral immune response in mice. Der Pharm Lett 2012;4:1868-73.
40. Tan YS, Nambiar R, Yo SL. Prevalence of protein calorie malnutrition ingeneral surgical estimating total serum lipid. Clin Chem 1992;18:199-202.
41. Sembulingam K, Sembulingam P. Essentials of Medical Physiology. 6th ed. Jaypee Brothers Medical Publishers Ltd.; 2012. p. 46-56.
42. Frandson RD. Anatomy and Physiology of Farms Animals. Ch. 31. Hoboken: Wiley; 2003. p. 462.
43. Hall JE. Guyton and Hall Textbook of Medical Physiology. 12th ed. Philadelphia, PA, 2011. p. 423-31.
44. Alnahdi HS. Injury in metabolic gland induced by pyrethroid insecticide could be reduced by aqueous of Sassura lappa. Int J Pharm Res Allied Sci 2017;6:86-97.
45. Choi EM, Kim GH, Lee YS. Protective effects of dehydrocostus lactone against hydrogen peroxide-induced dysfunction and oxidative stress in osteoblastic MC3T3-E1 cells. Toxicol In Vitro 2009;23:862-7.
46. Kang JS, Yoon YD, Lee KH, Park SK, Kim HM. Costunolide inhibits interleukin-1beta expression by down-regulation of AP-1 and MAPK activity in LPS-stimulated RAW 264.7 cells. Biochem Biophys Res Commun 2004;313:171-7. Hamilton AC. Medicinal Plants, Conservation and Livelihoods. Biodivers Conserv 2004;13:1477-517.
47. Valentine BA, Blue JT, Shelley SM, Cooper BJ. Increased serum alanine aminotransferase activity associated with muscle necrosis in the dog. J Vet Intern Med 1990;4:140-3.
48. Dubey GP, Agrawal A, Dixit SP. Effect of Liv-52 on different biochemical parameters in alcoholic cirrhosis. Antiseptic 1994;91:205-8.
49. Kanchana N, Sadiq AM. Hepatoprotective effect of Plumbago zeylanica on paracetamol induced liver toxicity in rats. Int J Pharm Pharm Sci 2011;3:151-4.
50. Shabnam A, Mohammad AS, Mohammad M. Hepatocurative effect of Saussurea lappa C.B Clarke and Artemisia absinthium, Linn in chronic hepatitis B. J Young Pharm 2018;10:354-7.
51. Ravindran NT, Mohamed SA. Pharmacological activity of Ulva lactuca polyphenols fraction: Hepatoprotective and antioxidant activities against paracetamol-induced liver damage in rats. Asia J Pharm Clin Res 2019;12:55-8.
52. Mayne PD. The kidneys and renal calculi. In: Clinical Chemistry in Diagnosis and Treatment. 6th ed. London: Edward Arnold Publications; 1994. p. 2-24.
53. Mugford CA, Tarloff JB. The contribution of oxidation and deacetylation to acetaminophen nephrotoxicity in female Sprague-Dawley rats. Toxicol Lett 1997;93:15-22.
54. Trumper L, Monasterolo LA, Elías MM. Nephrotoxicity of acetaminophen in male Wistar rats: Role of hepatically derived metabolites. J Pharmacol Exp Ther 1996;279:548-54.
55. Giri D, Das K, Nandi DK. Establishment of novel urinary disease new biomarkers and therapeutic effect of methanol fraction of Terminalia arjuna on acetaminophen induced kidney disease in rats. Asia J Pharm Clin Res 2019;12:117-24.
56. Adeneye AA, Benebo AS. Protective effect of the aqueous leaf and seed extract of Phyllanthus amarus on gentamicin and acetaminophen-induced nephrotoxic rats. J Ethnopharmacol 2008;118:318-23.
57. Parker EJ, Chuma SE, Chimere YU, Joshua OO, Prisca CO, Chinelo CN. Hepatocurative effect of aqueous extract of Hibiscus sabdariffa on some antioxidants and haematological indices of acetaminophen-challenged Wistar albino rats. Afr J Pharm Pharmacol 2017;11:250-9.
58. Gujral JS, Knight TR, Farhood A, Bajt ML, Jaeschke H. Mode of cell death after acetaminophen overdose in mice: Apoptosis or oncotic necrosis? Toxicol Sci 2002;67:322-8.
59. Fouad AA, Yacoubi MT, El-Bidawy MH. Therapeutic potential of hemin in acetaminophen nephrotoxicity in rats. Environ Toxicol Pharmacol 2009;27:277-82.
60. Khorsandi L, Orazizadeh M. Protective effects of Curcuma longa extract on acetaminophen inducedneph-rotoxicity in mice. DARU 2008;16:155-9.
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