Formulating a New Pharmaceutical Drug; Acetaminophen Tablet Containing N-acetyl Cysteine, To Alleviate the Severity of Liver Damage in Rats: Phase I, Animal Study

O. Mehrpour, M. Dastjerdi, Samaneh Nakhaee, Alireza Amirabadizadeh, B. Bijari, Hesam Roumi, Mehran Hosseini
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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
新药的研制;含n -乙酰半胱氨酸对乙酰氨基酚片减轻大鼠肝损伤的ⅰ期动物研究
背景与目的:对乙酰氨基酚(APAP)是一种常用的镇痛药,也是引起药物性肝损伤的主要原因。另一方面,n -乙酰半胱氨酸(NAC)是一种广泛用于治疗APAP过量的药物。尽管有这种兴趣,一些研究调查了这些药物的共同施用效果。因此,本研究旨在评价NAC和APAP同时使用时对大鼠肝肾功能的影响。方法:雄性Wistar大鼠口服单剂量APAP (700 mg/kg)或NAC(200、500、700 mg/kg)联合治疗。24小时后,采集血液和肝脏标本进行生化和组织病理学评价。结果:700 mg/kg apap处理大鼠肝损伤明显,血浆中谷草转氨酶(AST)和丙氨酸转氨酶(ALT)水平升高。此外,与对照组相比,APPA组血浆尿素氮(BUN)水平显著升高。此外,组织学检查显示,apap处理的动物肝脏变性明显。NAC仅在最高剂量(700 mg/kg)时能抑制ALT升高,但对AST和BUN水平无影响。有趣的是,NAC (700 mg/kg)和APAP (700 mg/kg)联合给药可以轻微地将肝脏组织学改变从不可逆阶段(纤维化)转变为可逆性病变,如坏死和出血。结论:NAC与APAP联合用药可减轻APAP所致大鼠肝损伤的严重程度。*通讯作者:Mehran Hosseini;电子邮件:mehranhosseiny@bums.ac.ir;ORCID: https://orcid.org/0000-0002-6793-2035本文署名:Mehrpour O, Dastjerdi M, Nakhaee S, Amirabadizadeh A, Bijari B, Roomi H, Hosseini M.新药配方;含n -乙酰半胱氨酸对乙酰氨基酚片减轻大鼠肝损伤的ⅰ期动物研究中华医学杂志,2011;7:1-8 (e14)。https://doi.org/10.22037/amls.v7.35528
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