The Role of Allium saralicum Extract on Prevention of Acetaminophen-Induced Hepatic Failure: an Experimental Study

Document Type : Original paper


1 Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran.

2 Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.Department of Pharmacognosy, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran.

3 Anatomy Department, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.


Background and objectives: Acetaminophen (APAP) is a common analgesic medicine whose overdose leads to severe hepatic dysfunction. Due to the known antioxidant properties of Alliumspecies, the present study aimed to evaluate the protective effects of Allium saralicum plant on APAP induced liver toxicity. Methods: The hydro-alcoholic extract of A. saralicum was prepared by maceration and ultrasonic methods. Forty-two rats in seven groups were treated by gavage as follows: groups 1 and 2 received normal saline, groups 3 received 400 mg/kg of A. saralicum hydro-alcoholic extract, and the groups 4-7 were treated with 50, 100, 200 and 400 mg/kg of A. saralicum extract, respectively. After two consecutive weeks, the therapeutic groups, as well as the positive control (APAP) group, were administered a single dose of APAP (2 g/kg). After 48 hours, the animals were anesthetized, and blood and liver samples were collected for histological and biochemical examinations.Results: Our findings indicated that APAP caused a significant rise in ALT (p<0.001), AST (p<0.001), ALP (p<0.001) and LDH (p<0.001) serum levels, total and direct bilirubin (p<0.001), hepatic lipid peroxidation (LPO; p<0.001) and nitric oxide (NO; p<0.001). In addition, APAP let to the decreasing of the total antioxidant capacity (TAC; p< 0.001), total thiol molecules (TTM; p<0.001), and structural changes in the hepatic tissue. Following administration ofA. saralicum extract, a remarkable improvement was observed in the functional and oxidative stress indices of liver tissue alongside histopathologic alterations. Conclusion: Our results showed that A. saralicum extractsignificantly improved APAP-induced hepatic failure through inhibition of oxidative/nitrosative stress.


Main Subjects

[1] McGill MR, Sharpe MR, Williams CD, Taha M, Curry SC, Jaeschke H. The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation. J Clin Invest. 2012; 122(4): 1574-1583.
[2] Nili-Ahmadabadi A, Borzouee Z, Ahmadimoghaddam D, Firozian F, Dastan D. The occurrence of acetaminophen/codeine as an adulterant in herbal analgesic supplements in Hamadan, Iran: A pilot study. Complement Ther Med. 2019; 42: 223-225.
[3] Nikles CJ, Yelland M, Del Mar C, Wilkinson D. The role of paracetamol in chronic pain. An evidence-based approach. Am J Ther. 2005; 12(1): 80-91.
[4] Toes MJ, Jones AL, Prescott L. Drug interactions with paracetamol. Am J Ther. 2005; 12(1): 56-66.
[5] Sanaei-Zadeh H, Taghaddosinejad F, Jalali N, Kariman H. Adverse effects of intravenous N-acetylcysteine. Clin Drug Investig. 2003; 23(2): 129-133.
[6] Chun LJ, Tong MJ, Busuttil RW, Hiatt JR. Acetaminophen hepatotoxicity and acute liver failure. J Clin Gastroenterol. 2009; 43(4): 342-349.
[7] Blieden M, Paramore LC, Shah D, Ben-Joseph R. A perspective on the epidemiology of acetaminophen exposure and toxicity in the United States. Expert Rev Clin Phar. 2014; 7(3): 341-348.
[8] McGill MR, Jaeschke H. Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharm Res. 2013; 30(9): 2174-2187.
[9] Abiko Y, Ishii I, Kamata S, Tsuchiya Y, Watanabe Y, Ihara H, Akaike T, Kumagai Y. Formation of sulfur adducts of N-acetyl-p-benzoquinoneimine, an electrophilic metabolite of acetaminophen in vivo: participation of reactive persulfides. Chem Res Toxicol. 2015; 28(9): 1796-1802.
[10] Laine JE, Auriola S, Pasanen M, Juvonen RO. Acetaminophen bioactivation by human cytochrome P450 enzymes and animal microsomes. Xenobiotica. 2009; 39(1): 11-21.
[11] Hinson JA, Reid AB, McCullough SS, James LP. Acetaminophen-induced hepatotoxicity: role of metabolic activation, reactive oxygen/nitrogen species, and mitochondrial permeability transition. Drug Metab Rev. 2004; 36(3-4): 805-822.
[12] Sherkatolabbasieh H, Hagh-Nazari L, Shafiezadeh S, Goodarzi N, Zangeneh MM, Zangeneh A. Ameliorative effects of the ethanolic extract of Allium saralicum RM Fritsch on CCl4-induced nephrotoxicity in mice: A stereological examination. Arch Biol Sci. 2017; 69(3): 535-543.
[13] Zhaleh M, Zangeneh MM, Zangeneh A, Moradi R, Zhaleh H. Antioxidant, cytotoxic, and wound healing effects of Allium saralicum RM Fritsch aqueous extract ointment in male rats: a gross, histological, and biochemical experiment. Comp Clin Path. 2019; 28(5): 1421-1429.
[14] Goorani S, Shariatifar N, Seydi N, Zangeneh A, Moradi R, Tari B, Nazari F, Zangeneh MM. The aqueous extract of Allium saralicum RM Fritsch effectively treat induced anemia: experimental study on Wistar rats. Orient Pharm Exp Med. 2019; 19(4): 403-413.
[15] Zangeneh MM, Bovandi S, Gharehyakheh S, Zangeneh A, Irani P. Green synthesis and chemical characterization of silver nanoparticles obtained using Allium saralicum aqueous extract and survey of in vitro antioxidant, cytotoxic, antibacterial and antifungal properties. Appl Organometal Chem. 2019; 33(7): 1-11.
[16] Jalalvand AR, Zhaleh M, Goorani S, Zangeneh MM, Seydi N, Zangeneh A, Moradi R. Chemical characterization and antioxidant, cytotoxic, antibacterial, and antifungal properties of ethanolic extract of Allium saralicum R.M. Fritsch leaves rich in linolenic acid, methyl ester. J Photoch Photobio B. 2019; 192: 103-112.
[17] Rybiński W, Karamać M, Sulewska K, Börner A, Amarowicz R. Antioxidant potential of grass pea seeds from European countries. Foods. 2018; 7(9): 1-11.
[18] Hu M, Dillard C. Plasma SH and GSH measurement. Methods Enzymol. 1994; 233: 385- 387.
[19] Nili-Ahmadabadi A, Ali-Heidar F, Ranjbar A, Mousavi L, Ahmadimoghaddam D, Larki-Harchegani A, Ghafouri-Khosrowshahi A. Protective effect of amlodipine on diazinon-induced changes on oxidative/antioxidant balance in rat hippocampus. Res Pharm Sci. 2018; 13(4): 368-376.
[20] Zeinvand-Lorestani H, Nili-Ahmadabadi A, Balak F, Hasanzadeh G, Sabzevari O. Protective role of thymoquinone against paraquat-induced hepatotoxicity in mice. Pestic Biochem Physiol. 2018; 148: 16-21.
[21] Okokon JE, Simeon JO, Umoh EE. Hepatoprotective activity of the extract of Homalium letestui stem against paracetamol-induced liver injury. Avicenna J Phytomed. 2017; 7(1): 27-36.
[22] Sadeghi H, Hosseinzadeh S, Touri MA, Ghavamzadeh M, Barmak MJ. Hepatoprotective effect of Rosa canina fruit extract against carbon tetrachloride induced hepatotoxicity in rat. Avicenna J Phytomed. 2016; 6(2): 181-188.
[23] Uchida NS, Silva-Filho SE, Cardia GF, Cremer E, Silva-Comar FM, Silva EL, Bersani-Amado CA, Cuman RK. Hepatoprotective effect of citral on acetaminophen-induced liver toxicity in mice. Evid Based Complement Altern Med. 2017; 2017(1-2): 1-9.
[24] Goorden S, Buffart T, Bakker A, Buijs M. Liver disorders in adults: ALT and AST. Ned Tijdschr Geneeskd. 2013; 157(43): 1-6.
[25] Ghobadi S, Dastan D, Soleimani M, Nili-Ahmadabadi A. Hepatoprotective potential and antioxidant activity of Allium tripedale in acetaminophen-induced oxidative damage. Res Pharm Sci. 2019; 14(6): 488-495.
[26] Nili-Ahmadabadi A, Alibolandi P, Ranjbar A, Mousavi L, Nili-Ahmadabadi H, Larki-Harchegani A, Ahmadimoghaddam D, Omidifar N. Thymoquinone attenuates hepatotoxicity and oxidative damage caused by diazinon: an in vivo study. Res Pharm Sci. 2018; 13(6): 500-508.
[27] Epstein E, Kiechle FL, Artiss JD, Zak B. The clinical use of alkaline phosphatase enzymes. Clin Lab Med. 1986; 6(3): 491-505.
[28] Mehri N, Felehgari H, Harchegani A, Behrooj H, Kheiripour N, Ghasemibasir H, Mirhoseini M, Ranjbar A. Hepatoprotective effect of the root extract of green tea against malathion-induced oxidative stress in rats. J HerbMed Pharmacol. 2016; 5(3): 116-119.
[29] Ferreira EA, Gris EF, Felipe KB, Correia JF, Cargnin-Ferreira E, Wilhelm Filho D, Pedrosa RC. Potent hepatoprotective effect in CCl4-induced hepatic injury in mice of phloroacetophenone from Myrcia multiflora. Libyan J Med. 2010; 5(1): 1-10.
[30] Abo-Haded HM, Elkablawy MA, Al-johani Z, Al-ahmadi O, El-Agamy DS. Hepatoprotective effect of sitagliptin against methotrexate induced liver toxicity. Plos One. 2017; 12(3): 1-16.
[31] Campos R, Garrido A, Guerra R, Valenzuela A. Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Med. 1989; 55(5): 417-419.
[32] Hsu C, Lin K, Wang Z, Lin W, Yin M. Preventive effect of Ganoderma amboinense on acetaminophen-induced acute liver injury. Phytomed. 2008; 15(11): 946-950.
[33] Küpeli E, Orhan DD, Yesilada E. Effect of Cistus laurifolius L. leaf extracts and flavonoids on acetaminophen-induced hepatotoxicity in mice. J Ethnopharmacol. 2006; 103(3): 455-460.
[34] Gardner CR, Heck DE, Yang CS, Thomas PE, Zhang XJ, DeGeorge GL, Laskin JD, Laskin DL. Role of nitric oxide in acetaminophen-induced hepatotoxicity in the rat. Hepatology. 1998; 27(3): 748-754.
[35] Goodarzi N, Zangeneh MM, Zangeneh A. The effect of ethanolic extract of Allium saralicum RM Fritsch on diabetic hepatopathy in male mice. Daneshvar Med. 2018; 25(132): 21-30.