Effects of pretreatment with anethole in a model of paracetamol-induced hepatotoxicity in rats
DOI:
https://doi.org/10.14748/h7gh9230Keywords:
Anethole, hepatotoxicity, paracetamol, rat model, liver enzymes, histopathologyAbstract
Introduction: Anethole is a volatile aromatic constituent predominantly present in essential oils, known with its antioxidant and anti-inflammatory activity.
Aim: The objective of the present research was to evaluate the preventive effects of anethole in a rat model of paracetamol (PM)-induced hepatotoxicity.
Materials and Methods: Male Wistar rats were randomly allocated to 5 groups (n = 10): Control, PM, PM+62.5AN, PM+125AN, and PM+250AN. For 10 days, the Control and PM group received sunflower oil orally, while the other groups—anethole at doses of 62.5 mg/kg, 125 mg/kg, and 250 mg/kg, respectively, dissolved in sunflower oil. On day 11, all groups except the Control received intraperitoneal PM (1 g/kg). After 48 hours, anthropometric parameters (liver weight and body weight) were measured and liver damage was assessed by biochemical analyses (AST and ALT serum activities) and histopathological investigation by light microscopy including a scoring method for necrosis severity.
Results and Conclusion: Administration of PM resulted in a marked decrease in body weight (p < 0.001 compared to the control group) and a significant elevation of AST (p < 0.01) and ALT (p < 0.001) levels. Liver tissue from PM group exhibited centrilobular coagulative necrosis and bridging necrosis. Pretreatment with anethole partially ameliorated liver injury, as demonstrated by lower AST activities in groups PM+62.5AN (p < 0.05 vs. PM) and PM+250AN (p < 0.01 vs. PM). Histopathological assessment indicated diminished hepatic damage with reduction of the necrotic areas. The liver necrosis score decreased in a dose-dependent manner in anethole-pretreated groups. The current research indicated a dose-dependent hepatoprotective effect of anethole in the model of acute PM-induced hepatotoxicity.
References
[1] Ayoub SS. Paracetamol (acetaminophen): a familiar drug with an unexplained mechanism of action. Temperature (Austin). 2021;8(4):351-371. doi: 10.1080/23328940.2021.1886392.
[2] Gerriets V, Patel P, Nappe TM. Acetaminophen. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.
[3] Lee WM. Acetaminophen (APAP) hepatotoxicity - isn't it time for APAP to go away? J Hepatol. 2017;67(6):1324-1331. doi: 10.1016/j.jhep.2017.07.005.
[4] Brown MJ, Ball JG, Wright MS, et al. Novel protective mechanisms for S-adenosyl-L-methionine against acetaminophen hepatotoxicity: improvement of key antioxidant enzymatic function. Toxicol Lett. 2012;212(3):320-8.
[5] Food and Drug Administration, HHS. Organ-specific warnings; internal analgesic, antipyretic, and antirheumatic drug products for over-the-counter human use; final monograph. Final rule. Fed Regist. 2009;74(81):19385-409.
[6] Jaeschke H, Williams CD, McGill MR, et al. Models of drug-induced liver injury for evaluation of phytotherapeutics and other natural products. Food Chem Toxicol. 2013;55:279-89. doi: 10.1016/j.fct.2012.12.063.
[7] Clark GS. An aroma chemical profile: anethole. Perfumer Flavorist. 1993;18(5):11-8.
[8] Marinov V, Valcheva-Kuzmanova S. Review on the pharmacological activities of anethole. Scr Sci Pharm. 2015;2(2):14-9. doi: 10.14748/ssp.v2i2.1141.
[9] Katyare SS, Satav JG. Impaired mitochondrial oxidative energy metabolism following paracetamol-induced hepatotoxicity in the rat. Br J Pharmacol. 1989;96(1):51-8. doi: 10.1111/j.1476-5381.1989.tb11783.x.
[10] Hwang J, Chang YH, Park JH, et al. Dietary saturated and monounsaturated fats protect against acute acetaminophen hepatotoxicity by altering fatty acid composition of liver microsomal membrane in rats. Lipids Health Dis. 2011;10:184. doi: 10.1186/1476-511X-10-184.
[11] Mach J, Huizer-Pajkos A, Cogger VC, et al. The effect of aging on acetaminophen pharmacokinetics, toxicity and Nrf2 in Fischer 344 rats. J Gerontol A Biol Sci Med Sci. 2014;69(4):387-97. doi: 10.1093/gerona/glt095.
[12] Sasidharan S, Aravindran S, Latha LY, et al. In vitro antioxidant activity and hepatoprotective effects of Lentinula edodes against paracetamol-induced hepatotoxicity. Molecules. 2010;15(6):4478-89. doi: 10.3390/molecules15064478.
[13] Gancheva S, Moneva-Marinova K, Eftimov M, et al. Effects of pretreatment with aqueous infusion of Kochia scoparia seeds in a model of paracetamol-induced hepatotoxicity in rats. Scr Sci Med. 2026;58(2). doi: 10.14748/9yfhs506.
[14] Islam MT, Quispe C, Islam MA, et al. Effects of nerol on paracetamol-induced liver damage in Wistar albino rats. Biomed Pharmacother. 2021;140:111732. doi: 10.1016/j.biopha.2021.111732.
[15] Yao P, Liu Y. Terpenoids: natural compounds for non-alcoholic fatty liver disease (NAFLD) therapy. Molecules. 2023;28(1):272. doi: 10.3390/molecules28010272.
[16] Imbabi T, Sabeq I, Osman A, et al. Impact of fennel essential oil as an antibiotic alternative in rabbit diet on antioxidant enzyme levels, growth performance, and meat quality. Antioxidants (Basel). 2021;10(11):1797.
[17] Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ. 2005;172(3):367-79. doi: 10.1503/cmaj.1040752.
[18] Noreen S, Rehman HU, Tufail T, et al. Secoisolariciresinol diglucoside and anethole ameliorate lipid abnormalities, oxidative injury, hypercholesterolemia, heart, and liver conditions. Food Sci Nutr. 2023;11:2620-30. doi: 10.1002/fsn3.3250.
[19] Pandit K, Kumar A, Kaur S, et al. Amelioration of oxidative stress by trans-anethole via modulating phase I and phase II enzymes against hepatic damage induced by CCl4 in male Wistar rats. Environ Sci Pollut Res Int. 2022;29:6317-33. doi: 10.1007/s11356-021-16070-z.
[20] Nazir T, Shakir L, Rahman ZU, et al. Hepatoprotective activity of Foeniculum vulgare against paracetamol-induced hepatotoxicity in rabbit. J Appl Pharm. 2020;12. doi: 10.35248/2376-0354.20.12.270.
[21] Tong Y, Yu C, Xie Z, et al. Trans-anethole ameliorates lipopolysaccharide-induced acute liver inflammation in broilers via inhibiting NF-κB signaling pathway. Poult Sci. 2022;101(8):101962. doi: 10.1016/j.psj.2022.101962.
[22] Lu J, Hou W, Yang S, et al. Trans-anethole pretreatment ameliorates hepatic ischemia-reperfusion injury via regulation of soluble epoxide hydrolase. Int Immunopharmacol. 2023;124:110809. doi: 10.1016/j.intimp.2023.110809.
[23] Mello A, Hsu MF, Koike S, et al. Soluble epoxide hydrolase hepatic deficiency ameliorates alcohol-associated liver disease. Cell Mol Gastroenterol Hepatol. 2021;11(3):815-30. doi: 10.1016/j.jcmgh.2020.10.002.
[24] da Rocha BA, Ritter AM, Ames FQ, et al. Acetaminophen-induced hepatotoxicity: preventive effect of trans-anethole. Biomed Pharmacother. 2017;86:213-20. doi: 10.1016/j.biopha.2016.12.014.
[25] Zhang C, Zhang B, Chen A, et al. Trans-anethole attenuates diet-induced nonalcoholic steatohepatitis through suppressing TGF-β-mediated fibrosis. Clin Res Hepatol Gastroenterol. 2022;46(4):101833. doi: 10.1016/j.clinre.2021.101833.
Downloads
Published
Data Availability Statement
The authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary materials
