The Prophylactic Anti-Inflammatory Effect of Omega-7 Against Paracetamol-Induced Liver Injury in Rats
Article Sidebar
Main Article Content
Abstract
Paracetamol poisoning, whether intentionally or accidentally, is one of the main public health problems since the prevalence of its toxicity increased significantly in many countries. Currently, paracetamol is one of the primary causes of acute liver failure worldwide. The aim of this study was to investigate the potential prophylactic effect of omega-7 fatty acid in protecting male rats' livers from paracetamol-induced liver damage. Thirty albino male rats were divided randomly and equally into five groups and then treated as follows: Group 1 (negative control) rats were orally given liquid paraffin for seven consecutive days. Group 2 (positive control) rats were orally given liquid paraffin for seven consecutive days and a single injection of paracetamol (500 mg/kg) intraperitoneally on day eight of the experiment. Group 3 rats were orally given omega-7 (300 mg/kg) for seven consecutive days. Group 4 rats were orally given a single dose of omega-7 (100 mg/kg/day) for 7 days and a single injection of paracetamol (500 mg/kg) intraperitoneally on day eight of the experiment. Group 5 rats were orally given a single dose of omega-7 (300 mg/kg/day) for 7 days and a single injection of paracetamol (500 mg/kg) intraperitoneally on day eight of the experiment. After 24 h of the endpoint of treatment (on day 9), blood samples were collected, and serum was prepared for the evaluation of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10). This study found that rats given paracetamol had a significant (P<0.05) increase in serum levels of TNF-α and IL-10, whereas rats previously given oral administration of omega-7 fatty acid before injection of paracetamol resulted in a significant decrease (P<0.05) of these cytokines. Oral omega-7 fatty acid supplementation may help to prevent liver damage caused by paracetamol.
Downloads
Article Details
How to Cite
References
Jacqz–Aigrain E, Anderson BJ. Pain control: Non–steroidal anti–inflammatory agents. Semin Fetal Neonatal Med. 2006;11(4):251–259. https://doi.org/10.1016/j.siny.2006.02.009
McGill MR, Jaeschke H. Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharm. Res. 2013; 30(9):2174–2187. https://doi.org/10.1007/s11095-013-1007-6
Zaher H, Buters JT, Ward JM, Bruno MK, Lucas AM, Stern ST, et al. Protection against acetaminophen toxicity in CYP1A2 and CYP2E1 double–null mice. Toxicol. Appl. Pharmacol. 1998; 152(1):193–199. https://doi.org/10.1006/taap.1998.8501
Ramachandran A, Jaeschke H. Mechanisms of acetaminophen hepatotoxicity and their translation to the human pathophysiology. JDR Clin Trans Res. 2017; 3(1):157. https://doi.org/10.18053/jctres.03.2017S1.002
Ghanem CI, Pérez MJ, Manautou JE, Mottino AD. Acetaminophen from liver to brain: New insights into drug pharmacological action and toxicity. Pharmacol. Res. 2016; 109:119–131. https://doi.org/10.1016/j.phrs.2016.02.020
Hamad ZM. Protective role of Nigella sativa oil on renal damage induced by acetaminophen in male rats. Iraqi J. Vet. Med. 2016; 40(2):77–81. https://doi.org/10.30539/iraqijvm.v40i2.116
Offor SJ, Amadi CN, Chijioke–Nwauche I, Manautou JE, Orisakwe OE. Potential Deleterious Effects of Paracetamol Dose Regime Used in Nigeria Versus That of the United States of America. Toxicol. Rep. 2022. https://doi.org/10.1016/j.toxrep.2022.04.025
Kim YR, Lee NJ, Ban JO, Yoo HS, Lee YM, Yoon YP, et al. Curative effects of thiacremonone against acetaminophen–induced acute hepatic failure via inhibition of proinflammatory cytokines production and infiltration of cytotoxic immune cells and Kupffer cells. Evid. Based Complementary Altern. Med. 2013;2013. https://doi.org/10.1155/2013/974794
Michael SL, Mayeux PR, Bucci TJ, Warbritton AR, Irwin LK, Pumford NR, et al. Acetaminophen–induced hepatotoxicity in mice lacking inducible nitric oxide synthase activity. Nitric oxide. 2001; 5(5):432–441. https://doi.org/10.1006/niox.2001.0385
Martin–Murphy BV, Holt MP, Ju C. The role of damage associated molecular pattern molecules in acetaminophen–induced liver injury in mice. Toxicol. lett. 2010; 192(3):387–394. https://doi.org/10.1016/j.toxlet.2009.11.016
Majeed IA, Al–Shawi NN. Effects of omega–3 co–administered with therapeutic dose of lornoxicam on male rats' liver. Iraqi J Pharm. Sci. 2019; 28(2):159–164. https://doi.org/10.31351/vol28iss2pp159-164
Jang DI, Lee AH, Shin HY, Song HR, Park JH, Kang TB, et al. The role of tumor necrosis factor alpha (TNF–α) in autoimmune disease and current TNF–α inhibitors in therapeutics. Int J Mol Sci. 2021; 22(5):2719. https://doi.org/10.3390/ijms22052719
da Rocha BA, Ritter AM, Ames FQ, Gonçalves OH, Leimann FV, Bracht L, et al. Acetaminophen–induced hepatotoxicity: preventive effect of trans anethole. Biomed. Pharmacother. 2017; 86:213–20. https://doi.org/10.1016/j.biopha.2016.12.014
Mukherjee KD, Kiewitt I. Formation of (n–9) and (n–7) cis–monounsaturated fatty acids in seeds of higher plants. Planta. 1980; 149(5):461–463. https://doi.org/10.1007/BF00385748
Nguyen HT, Park H, Koster KL, Cahoon RE, Nguyen HTM, Shanklin J, et al. Redirection of metabolic flux for high levels of omega–7 monounsaturated fatty acid accumulation in camelina seeds. Plant Biotechnol J. 2015; 13(1):38–50. https://doi.org/10.1111/pbi.12233
Mozaffarian D, Cao H, King IB, Lemaitre RN, Song X, Siscovick DS, et al. Trans–palmitoleic acid, metabolic risk factors, and new–onset diabetes in US adults: a cohort study. Ann Intern Med. 2010;153(12):790–799. https://doi.org/10.7326/0003-4819-153-12-201012210-00005
Bernstein AM, Roizen MF, Martinez L. RETRACTED: Purified palmitoleic acid for the reduction of high–sensitivity C–reactive protein and serum lipids: A double–blinded, randomized, placebo controlled study. J Clin Lipidol. 2014; 6(8):612–617. https://doi.org/10.1016/j.jacl.2014.08.001
Stefan N, Kantartzis K, Celebi N, Staiger H, Machann J, Schick F, et al. Circulating palmitoleate strongly and independently predicts insulin sensitivity in humans. Diabetes care. 2010;33(2):405–7. https://doi.org/10.2337/dc09-0544
Guo X, Li H, Xu H, Halim V, Zhang W, Wang H, et al. Palmitoleate induces hepatic steatosis but suppresses liver inflammatory response in mice. PLoS One. 2012; 7(6):39286. https://doi.org/10.1371/journal.pone.0039286
Curb JD, Wergowske G, Dobbs JC, Abbott RD, Huang B. Serum lipid effects of a high–monounsaturated fat diet based on macadamia nuts. Arch. Intern. Med. 2000;160(8):1154–1158. https://doi.org/10.1001/archinte.160.8.1154
de Souza CO, Teixeira AA, Biondo LA, Lima Junior EA, Batatinha HA, Rosa Neto JC. Palmitoleic acid improves metabolic functions in fatty liver by PPARα‐dependent AMPK activation. J Cell Physiol. 2017; 232(8):2168–2177. https://doi.org/10.1002/jcp.25715
Hasanein P, Sharifi M. Effects of rosmarinic acid on acetaminophen–induced hepatotoxicity in male Wistar rats. Pharm. Biol. 2017; 55(1):1809–1816. https://doi.org/10.1080/13880209.2017.1331248
Meganathan M, Gopal KM, Sasikala P, Mohan J, Gowdhaman N, Balamurugan K, et al. Evaluation of hepatoprotective effect of omega 3–fatty acid against paracetamol induced liver injury in albino rats. Glob J Pharmacol. 2011; 5(1):50–53.
Gunnell D, Hawton K, Murray V, Garnier R, Bismuth C, Fagg J, Simkin S. Use of paracetamol for suicide and non–fatal poisoning in the UK and France: are restrictions on availability justified? J. Epidemiology Community Health. 1997; 51(2):175–179. https://doi.org/10.1136/jech.51.2.175
Robinson D, Smith AM, Johnston GD. Severity of overdose after restriction of paracetamol availability: retrospective study. Br Med J. 2000; 321(7266):926–927. https://doi.org/10.1136/bmj.321.7266.926
Ostapowicz G, Fontana RJ, Schiødt FV, Larson A, Davern TJ, Han SH, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann. Intern Med. 2002;137(12):947–954. https://doi.org/10.7326/0003-4819-137-12-200212170-00007
Mohamed Kamel GA, Harahsheh E, Hussein S. Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF–κB and upregulating PPAR–γ signal. Mol Biol Rep. 2022; 49(7):5863–5874. https://doi.org/10.1007/s11033-022-07366-5
Fu T, Wang S, Liu J, Cai E, Li H, Li P, Zhao Y. Protective effects of α–mangostin against acetaminophen–induced acute liver injury in mice. Eur. Pharmacol. 2018; 827:173–180. https://doi.org/10.1016/j.ejphar.2018.03.002
Bian X, Wang S, Liu J, Zhao Y, Li H, Zhang L, et al. Hepatoprotective effect of chiisanoside against acetaminophen–induced acute liver injury in mice. Nat Prod Res. 2019; 33(18):2704–2707. https://doi.org/10.1080/14786419.2018.1460841
Du K, Ramachandran A, Jaeschke H. Oxidative stress during acetaminophen hepatotoxicity: Sources, pathophysiological role and therapeutic potential. Redox Biol. 2016; 10:148–156. https://doi.org/10.1016/j.redox.2016.10.001
Mihm S. Danger–associated molecular patterns (DAMPs): molecular triggers for sterile inflammation in the liver. Int J Mol Sci. 2018; 19(10):3104. https://doi.org/10.3390/ijms19103104
Yang S, Kuang GE, Jiang R, Wu S, Zeng T, Wang Y, et al. Geniposide protected hepatocytes from acetaminophen hepatotoxicity by down–regulating CYP2E1 expression and inhibiting TLR4/NF–κB signaling pathway. Int Immunopharmacol. 2019; 74:105625. https://doi.org/10.1016/j.intimp.2019.05.010
Hammerich L, Tacke F. Interleukins in chronic liver disease: lessons learned from experimental mouse models. Clin Exp Gastroenterol. 2014; 7:297. https://doi.org/10.2147/CEG.S43737
Bourdi M, Masubuchi Y, Reilly TP, Amouzadeh HR, Martin JL, George JW, Shah AG, Pohl LR. Protection against acetaminophen–induced liver injury and lethality by interleukin 10: role of inducible nitric oxide synthase. J Hepatol. 2002; 35(2):289–298. https://doi.org/10.1053/jhep.2002.30956
Yan SL, Wu ST, Yin MC, Chen HT, Chen HC. Protective effects from carnosine and histidine on acetaminophen–induced liver injury. J Food Sci. 2009; 74(8):H259-H265. https://doi.org/10.1111/j.1750-3841.2009.01330.x
Yang ZH, Miyahara H, Hatanaka A. Chronic administration of palmitoleic acid reduces insulin resistance and hepatic lipid accumulation in KK–Ay Mice with genetic type 2 diabetes. Lipids Health Dis. 2011;10(1):1–8. https://doi.org/10.1186/1476-511X-10-120
Souza CO, Teixeira AA, Lima EA, Batatinha HA, Gomes LM, Carvalho–Silva M, et al. Palmitoleic acid (n–7) attenuates the immunometabolic disturbances caused by a high–fat diet independently of PPARα. Mediators Inflamm. 2014; 2014:582197. https://doi.org/10.1155/2014/582197
Weimann E, Silva MBB, Murata GM, Bortolon JR, Dermargos A, Curi R, et al. Topical anti-inflammatory activity of palmitoleic acid improves wound healing. PLoS ONE. 13(10):e0205338. https://doi.org/10.1371/journal.pone.0205338