Hepatoprotective effect of Crocus sativus (saffron) petals extract against acetaminophen toxicity in male Wistar rats

Document Type : Original Research Article


1 Department of Animal Health Management, School of Veterinary Medicine, Shiraz University, I. R. Iran

2 Department of Animal Sciences, Agriculture Faculty, Birjand University, Birjand, I. R. Iran

3 Saffron Research Group, Birjand University, Birjand, I. R. Iran


Objectives: Acetaminophen (APAP) toxicity is known to be common and potentially fatal. This study aims to investigate the protective effects of hydroalcoholic extract, remaining from Crocus sativus petals (CSP) against APAP-induced hepatotoxicity by measuring the blood parameters and studying the histopathology of liver in male rats.
Materials and Methods: Wister rats (24) were randomly assigned into four groups including: I) healthy, receiving normal saline; II) Intoxicated, receiving only APAP (600 mg/kg); III) pre-treated with low dose of CSP (10 mg /kg) and receiving APAP (600 mg/kg); IV) pre-treated with high dose of CSP (20 mg/kg) and receiving APAP (600 mg/kg).
Results: The APAP treatment resulted in higher levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin, along with lower total protein and albumin concentration than the control group. The administration of CSP with a dose of 20 mg/kg was found to result in lower levels of AST, ALT and bilirubin, with a significant higher concentration of total protein and albumin. The histopathological results regarding liver pathology, revealed sever conditions including cell swelling, severe inflammation and necrosis in APAP-exposed rats, which was quiet contrasting compared to the control group. The pre-treated rats with low doses of ‍CSP showed hydropic degeneration with mild necrosis in centrilobular areas of the liver, while the same subjects with high doses of ‍CSP appeared to have only mild hepatocyte degeneration.
Conclusions: Doses of 20 mg/kg of CSP ameliorates APAP–induced acute liver injury in rats. It was concluded that the antioxidant property of CSP resulted in reducing the oxidative stress complications of toxic levels of APAP in intoxicated rats.


Abdullaev FI. 2002. Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.). Exp Biol Med, 227: 20-25.
Arias IM. 2012. Liver function from Y to Z. J Clin Investig, 122: 2763–2764.
Arnaiz S. 1995. Oxidative stress by acute acetaminophen administration in mouse liver. Free Radical Bio Med, 19:303–310.
Azizi-Zohan A, Kamgar-Haghighi AA, Sepaskhah AR. 2008. Crop and pan coefficients for saffron in a semi-arid region of Iran. J Arid Environ, 72: 270–278.
Babaei A, Arshami J, Haghparast A, Daneshmesgharan M. 2014. Effects of saffron (Crocus sativus) petal ethanolic extract on hematology, antibody response, and spleen histology in rats. Avicenna J Phytomed, 4: 130-109.
Barle H, Hammarqvist F, Westman B, Klaude M, Rooyackers O, Garlick PJ, et al. 2006. Synthesis rates of total liver protein and albumin are both increased in patients with an acute inflammatory response. Clin sci, 110: 93–99.
Bechmann LP, Hannivoort RA, Gerken G, Hotamisligil GS, Trauner M, Canbay A. 2012. The interaction of hepatic lipid and glucose metabolism in liver diseases. J Hepatol, 56: 952–964.
Bunchorntavakul C, Reddy KR. 2013. Acetaminophen-related Hepatotoxicity. Clin Liver Dis,17: 587–607.
Goli SAH, Mokhtari F, Rahimmalek M. 2012. Phenolic Compounds and Antioxidant Activity from Saffron (Crocus sativus L.) Petal. J Agr Sci, 4: 175.
Hinson J, Roberts D, James L. 2010. Mechanisms of Acetaminophen-Induced Liver Necrosis. In: Uetrecht J, editor. Adverse Drug Reactions. vol. 196 of Handbook of Experimental Pharmacology. Berlin, Heidelberg: Springer Berlin Heidelberg. p. 369–405.
Hodgman MJ, Garrard AR. 2012. A review of acetaminophen poisoning. Crit Care clin, 28: 499–516.
Hosseinzadeh H, Nassiri-Asl M. 2013. Avicenna’s (Ibn Sina) the Canon of Medicine and saffron (Crocus sativus): a review. Phytothe Res, 27: 475–483.
Lee W, Drug-induced hepatotoxicity. 2003. New Eng J Med, 49: 474-85.
Lu Y, Sun J, Petrova K, Yang X, Greenhaw J, Salminen WF, et al. 2013. Metabolomics evaluation of the effects of green tea extract on acetaminophen-induced hepatotoxicity in mice. Food Chem Ttoxicol, 62: 707–721.
Malloy HT, Evelyn KA 1949. The determination of bilirubin with photometric colorimeter. J Biol Chem, 4: 481-90.
Melnyk JP, Wang S, Marcone MF. 2010. Chemical and biological properties of the world’s most expensive spice: Saffron. Food Res Int, 43: 1981–1989.
Moshiri E, Basti AA, Noorbala AA, Jamshidi AH, Hesameddin Abbasi S, Akhondzadeh S. 2006. Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: A double-blind, randomized and placebo-controlled trial. Phytomedicine, 13: 607–611.
Nam KN, Park YM, Jung HJ, Lee JY, Min BD, Park SU, et al. 2010. Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells. Eur J Pharmacol, 648: 110–116.
Olaleye MT, Rocha BTJ. 2008. Acetaminophen-induced liver damage in mice: Effects of some medicinal plants on the oxidative defense system. Exp Toxicol Pathol, 59: 319–327.
Omidi A, Torabi Z, Hassanpoorfard M, Zardast M. 2013. Evaluation of protective effect of hydroalcoholic extract of Crocus sativus petals on preventing of gentamicin induced peliosishepatis and hepatic telangiectasis in rats: short communication. J Birjand Uni Med Scie, 19 : 455-462. [persian].
Pimple BP, Kadam PV, Badgujar NS, Bafna AR, Patil MJ. 2007. Protective effect of Tamarindus indica linn against paracetamol-induced hepatotoxicity in rats. Indian J Pharm Sci, 69: 827.
Poma A, Fontecchio G, Carlucci G, Chichiriccò G. 2012. Anti-inflammatory properties of drugs from saffron crocus. Antiinflamm Antiallergy Agents Med Chem, 11: 37–51.
Reitman S, Frankel SA. 1957. Chlorimetric method for determination of serum glutamic oxaloacetic and glutamic pyruvate transaminases. Am J Clin Pathol, 28: 56-63.
Schmidt M, Betti G, Hensel A. 2007. Saffron in phytotherapy: Pharmacology and clinical uses. Wien Med Wochenschr, 157: 315–319
Shah AD, Wood DM, Dargan PI. 2011. Understanding lactic acidosis in paracetamol (acetaminophen) poisoning. British J Clin Pharmaco,71: 20–28.
Tamaddonfard E, Farshid AA, Maroufi S, Kazemi-Shojaei S, Erfanparast A, Asri-Rezaei S, et al. 2014. Effects of safranal, a constituent of saffron, and vitamin E on nerve functions and histopathology following crush injury of sciatic nerve in rats. Phytomedicine,  21: 717-723.
Tan SC, New LS, Chan ECY. 2008. Prevention of acetaminophen (APAP)-induced hepatotoxicity by leflunomide via inhibition of APAP biotransformation to N-acetyl-p-benzoquinone imine. Toxicol Lett, 180: 174–181.
Termentzi A, Kokkalou E. 2008. LC-DAD-MS (ESI+) analysis and antioxidant capacity of crocus sativus petal extracts. Planta Med, 74: 573–581.
Trujillo J, Chirino YI, Molina-Jijón E, Andérica-Romero AC, Tapia E, Pedraza-Chaverrí J. 2013. Renoprotective effect of the antioxidant curcumin: Recent findings. Redox Biol, 1: 448–456.