Gomaa Mahmoud, Samy Saber, Samah Loutfy, Walaa Salama, A. Nabeeh
{"title":"埃及角蝰LAAO对大鼠肝细胞癌的治疗作用","authors":"Gomaa Mahmoud, Samy Saber, Samah Loutfy, Walaa Salama, A. Nabeeh","doi":"10.4103/epj.epj_48_23","DOIUrl":null,"url":null,"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.","PeriodicalId":11568,"journal":{"name":"Egyptian Pharmaceutical Journal","volume":null,"pages":null},"PeriodicalIF":0.7000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Therapeutic effects of the Egyptian horned viper LAAO against hepatocellular carcinoma induced in rats\",\"authors\":\"Gomaa Mahmoud, Samy Saber, Samah Loutfy, Walaa Salama, A. Nabeeh\",\"doi\":\"10.4103/epj.epj_48_23\",\"DOIUrl\":null,\"url\":null,\"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.\",\"PeriodicalId\":11568,\"journal\":{\"name\":\"Egyptian Pharmaceutical Journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.7000,\"publicationDate\":\"2023-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Egyptian Pharmaceutical Journal\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.4103/epj.epj_48_23\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Egyptian Pharmaceutical Journal","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4103/epj.epj_48_23","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Therapeutic effects of the Egyptian horned viper LAAO against hepatocellular carcinoma induced in rats
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.