Formulating a New Pharmaceutical Drug; Acetaminophen Tablet Containing N-acetyl Cysteine, To Alleviate the Severity of Liver Damage in Rats: Phase I, Animal Study
Archives of Medical Laboratory Sciences,
Vol. 7 (2021),
13 March 2021
,
Page 1-8 (e14)
https://doi.org/10.22037/amls.v7.35528
Abstract
Background and Aim: Acetaminophen (APAP) is a commonly used analgesic and also the leading cause of medication-induced liver damage. On the other hand, N-acetylcysteine (NAC) is a medication widely used to treat APAP overdose. Despite this interest, a few studies have investigated the co-administration effects of these medications. Therefore, this study aimed to evaluate the effects of NAC and APAP on renal and liver functions in rats when they use concurrently.
Methods: Male Wistar rats were orally treated with a single dose of APAP (700 mg/kg) alone or in combination of NAC at the three different doses (200, 500, and 700 mg/kg). After 24 hours, the blood and liver samples were collected for biochemical and histopathological evaluations.
Results: Liver damage was well established in the 700 mg/kg APAP-treated rats, as evidenced by elevated the plasma levels of aspartate transaminase (AST) and alanine transaminase (ALT). In addition, the plasma level of blood urea nitrogen (BUN) was significantly increased in the APPA group compared to the control group. Moreover, histological examinations revealed that liver degeneration was evident in APAP-treated animals. NAC only at the highest dose (700 mg/kg) could inhibit ALT elevation, but had no effect on AST and BUN levels. Interestingly, co-administration of NAC (700 mg/kg) with APAP (700 mg/kg) could slightly shift liver histological alterations from the irreversible stage (fibrosis) toward reversible lesions such as necrosis and hemorrhage.
Conclusion: The study findings indicate that co-administration of NAC and APAP can reduce the severity of APAP-induced liver damage in rats.
*Corresponding Author: Mehran Hosseini; Email: mehranhosseiny@bums.ac.ir;
ORCID: https://orcid.org/0000-0002-6793-2035
Please cite this article as: Mehrpour O, Dastjerdi M, Nakhaee S, Amirabadizadeh A, Bijari B, Roomi H, Hosseini M. Formulating a New Pharmaceutical Drug; Acetaminophen Tablet Containing N-acetyl Cysteine, To Alleviate the Severity of Liver Damage in Rats: Phase I, Animal Study. Arch Med Lab Sci. 2021;7:1-8 (e14). https://doi.org/10.22037/amls.v7.35528
- Acetaminophen
- Acetylcysteine
- Drug Interaction
- Drug-Induced Acute Liver Injury
How to Cite
References
Saljoughian M. Acetaminophen intoxication: a critical-care emergency. US Pharm. 2016;41(12):38-41.
Yoon E, Babar A, Choudhary M, Kutner M, Pyrsopoulos N. Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update. J Clin Transl Hepatol. 2016;4(2):131-42.
Chun BJ, Moon JM, Kim SH. Antidote for acetaminophen poisoning: N-acetylcysteine. J Korean Med Assoc. 2013;56(12):1067-75.
Mokhtari V, Afsharian P, Shahhoseini M, Kalantar SM, Moini A. A Review on Various Uses of N-Acetyl Cysteine. Cell J. 2017;19(1):11-7.
Pei YP, Liu H, Yang Y, Yang YW, Jiao Y, Tay FR, et al. Biological Activities and Potential Oral Applications of N-Acetylcysteine: Progress and Prospects. Oxidative Medicine and Cellular Longevity. 2018;2018:2835787.
Wang L, Wang ZY, Liu JZ. Protective effect of N-acetylcysteine on experimental chronic lead nephrotoxicity in immature female rats. Human & Experimental Toxicology. 2010;29(7):581-91.
Demedts M, Behr J, Buhl R, Costabel U, Dekhuijzen R, Jansen HM, et al. High-dose acetylcysteine in idiopathic pulmonary fibrosis. New England Journal of Medicine. 2005;353(21):2229-42.
Dodd S, Dean O, Copolov DL, Malhi GS, Berk M. N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert Opin Biol Ther. 2008;8(12):1955-62.
Girouard H, Chulak C, Wu L, Lejossec M, De Champlain J. N-acetylcysteine improves nitric oxide and α-adrenergic pathways in mesenteric beds of spontaneously hypertensive rats. American journal of hypertension. 2003;16(7):577-84.
Millea PJ. N-Acetylcysteine: Multiple Clinical Applications. American Family Physician. 2009;80(3):265-9.
Kerr F, Dawson A, Whyte IM, Buckley N, Murray L, Graudins A, et al. The Australasian Clinical Toxicology Investigators Collaboration randomized trial of different loading infusion rates of N-acetylcysteine. Ann Emerg Med. 2005;45(4):402-8.
Mehrpour O, Ballali-Mood M. Why not formulate an acetaminophen tablet containing N-acetylcysteine to prevent poisoning? Journal of Medical Toxicology. 2011;7(1): 95–6.
Owumi SE, Andrus JP, Herzenberg LA, Herzenberg LA. Co-administration of N-Acetylcysteine and Acetaminophen Efficiently Blocks Acetaminophen Toxicity. Drug Development Research. 2015;76(5):251-8.
Nakhaee S, Dastjerdi M, Roumi H, Mehrpour O, Farrokhfall K. N-acetylcysteine dose-dependently improves the analgesic effect of acetaminophen on the rat hot plate test. BMC Pharmacology and Toxicology. 2021;22(1):4.
Hassanzadeh-Taheri M, Hosseini M, Salimi M, Moodi H, Dorranpour D. Acute and sub-acute oral toxicity evaluation of Astragalus hamosus seedpod ethanolic extract in Wistar rats. Pharmaceutical Sciences. 2018;24(1):23-30.
Greene SC, Noonan PK, Sanabria C, Peacock WF. Effervescent N-Acetylcysteine Tablets versus Oral Solution N-Acetylcysteine in Fasting Healthy Adults: An Open-Label, Randomized, Single-Dose, Crossover, Relative Bioavailability Study. Current therapeutic research, clinical and experimental. 2016;83:1-7.
Mast C, Pourpe C, Voyard G, Remond D, Migne C, Centeno D, et al. Dietary supplementation with cysteine prevents adverse metabolic outcomes of repeated cures with paracetamol in old rats. The British journal of nutrition. 2017;118(11):889-96.
Hassanzadeh-Taheri M, Hassanpour-Fard M, Doostabadi M, Moodi H, Vazifeshenas-Darmiyan K, Hosseini M. Co-administration effects of aqueous extract of turnip leaf and metformin in diabetic rats. Journal of traditional and complementary medicine. 2018;8(1):178-83.
Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran pathologic basis of disease. 9th ed. Elsevier. 2014. p.610-621.
- Abstract Viewed: 412 times
- PDF Downloaded: 314 times