Therapeutic effects of the Egyptian horned viper LAAO against hepatocellular carcinoma induced in rats

IF 0.7 Q4 PHARMACOLOGY & PHARMACY
Gomaa Mahmoud, Samy Saber, Samah Loutfy, Walaa Salama, A. Nabeeh
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引用次数: 0

Abstract

Background The most common kind of liver cancer, hepatocellular carcinoma (HCC), is the fourth leading cause of cancer-related mortality worldwide and has poor prognosis. Strong hepatocarcinogen diethyl nitrosamine (DENA) is a well-known substance. It is well known that DENA damages DNA repair enzymes and is typically used to cause liver cancer in experimental animal models, such as rats. Cerastes cerastes L-amino acid oxidase (Cc-LAAO) has hepatoprotective, antioxidant, and anticancer effects. Objective To assess the effectiveness of L-amino acid oxidase (LAAO) as a hepatoprotective agent in comparison to paclitaxel (PAC) as a conventional anticancer medicine in the early identification of HCC using biomarkers [alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA)], various liver function tests, and oxidant and antioxidant tests. Materials and methods CCl4 (200 mg/kg b.wt.) was injected subcutaneously once a week for 3 weeks after a single IP dose of DENA (200 mg/kg b.wt.) to develop hepatocellular cancer in rats. Twenty-five adult, mature, healthy rats were used in this investigation; their average weight was 100±10 g, and they were divided into five groups, each with five rats. After the experiment, some hepatic tests, histology of the liver, a tumor biomarker, and some kidney functions were assessed for all groups. Results and conclusion ASAT, ALAT, ALP, total bilirubin, tumor markers AFP, CEA, and lipid peroxides malondialdehyde (MDA) significantly rose in serum after DENA administration in rats, whereas activating antioxidants like SOD, CAT, GPx, and GSH decreased. LAAO and paclitaxel significantly ameliorated biomarkers for liver damage, lipid peroxides (MDA), antioxidants such as (SOD), (CAT), (GSH), (GPx), tumor marker (AFP), and (CEA) compared with the HCC group. Histopathology showed vacuolar hepatocytes with dispersed hepatocyte necrosis and infiltration of mononuclear cells. When used with DENA, the LAAO administration reduced negative effects and produced positive effects. These findings demonstrate that LAAO prevents liver HCC caused by DEN by preventing lipid peroxidation, hepatic cell oxidative stress, and boosting the antioxidant system.
埃及角蝰LAAO对大鼠肝细胞癌的治疗作用
肝细胞癌(HCC)是最常见的一种肝癌,是全球癌症相关死亡的第四大原因,预后较差。强肝癌致癌物二乙基亚硝胺(DENA)是一种众所周知的物质。众所周知,DENA会破坏DNA修复酶,在大鼠等实验动物模型中通常被用于导致肝癌。蓖麻l -氨基酸氧化酶(Cc-LAAO)具有保护肝脏、抗氧化和抗癌作用。目的评价l -氨基酸氧化酶(LAAO)作为肝保护剂与紫杉醇(PAC)作为常规抗癌药物在肝癌早期诊断中的作用,采用生物标志物[甲胎蛋白(AFP)和癌胚抗原(CEA)]、各种肝功能检查以及氧化和抗氧化试验。材料与方法在单次单剂量DENA (200 mg/kg b.wt.)后,每周一次皮下注射CCl4 (200 mg/kg b.wt.),持续3周。本研究选用25只成年、成熟、健康大鼠;平均体重100±10 g,分为5组,每组5只大鼠。实验结束后,对所有组进行一些肝脏检查、肝脏组织学、肿瘤生物标志物和一些肾功能评估。结果与结论给药后大鼠血清ASAT、ALAT、ALP、总胆红素、肿瘤标志物AFP、CEA、脂质过氧化物丙二醛(MDA)显著升高,SOD、CAT、GPx、GSH等活性抗氧化剂显著降低。与HCC组相比,LAAO和紫杉醇显著改善了肝损伤生物标志物、脂质过氧化物(MDA)、抗氧化剂(SOD)、(CAT)、(GSH)、(GPx)、肿瘤标志物(AFP)和(CEA)。病理组织学表现为空泡型肝细胞,肝细胞分散坏死,单核细胞浸润。当与DENA一起使用时,LAAO管理减少了负面影响并产生了积极影响。这些发现表明,LAAO通过防止脂质过氧化、肝细胞氧化应激和增强抗氧化系统来预防DEN引起的肝细胞肝癌。
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来源期刊
Egyptian Pharmaceutical Journal
Egyptian Pharmaceutical Journal PHARMACOLOGY & PHARMACY-
CiteScore
1.10
自引率
0.00%
发文量
37
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