Vanillic acid protects mortality and toxicity induced by N-ethyl-N-nitrosourea in mice; in vivo model of chronic lymphocytic leukemia

Alkylating agents such as N-Ethyl-N-Nitrosourea (ENU) are ubiquitous within living cells and in the environment. This study designed to evaluate the chemopreventive activity of vanillic acid on ENU-induced toxicity and carcinogenesis in mice as an animal model of chronic lymphocytic leukemia (CLL)....

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Main Authors: Ahmad Salimi, Shadi Haddadi, Saleh Khezri, Bahare Asgari, Mahshad Pourgholi
Format: Article
Language:English
Published: Elsevier 2024-06-01
Series:Toxicology Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2214750024000374
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author Ahmad Salimi
Shadi Haddadi
Saleh Khezri
Bahare Asgari
Mahshad Pourgholi
author_facet Ahmad Salimi
Shadi Haddadi
Saleh Khezri
Bahare Asgari
Mahshad Pourgholi
author_sort Ahmad Salimi
collection DOAJ
description Alkylating agents such as N-Ethyl-N-Nitrosourea (ENU) are ubiquitous within living cells and in the environment. This study designed to evaluate the chemopreventive activity of vanillic acid on ENU-induced toxicity and carcinogenesis in mice as an animal model of chronic lymphocytic leukemia (CLL). The female, Swiss albino mice were divided into three groups each with 7 mice, group I received normal saline, group II, mice received ENU at a dose of 80 mg/kg body weight i.p. to induce CLL on the 31th day of the study, and group III, the mice pretreated with vanillic acid at a dose of 20 mg/kg body weight/day, i.p. up to 30 days and received ENU. The animals were monitored for weight changes and mortality during 120 days, and then were sacrificed for isolation of lymphocytes, as target cells in CLL. Cellular parameters like reactive oxygen species (ROS) formation, malondialdehyde (MDA) production, depletion of glutathione (GSH), mitochondrial membrane potential (MMP) and lysosomal membrane integrity were studied. We found that pretreatment with vanillic acid significantly increased the survival of mice up to 57%, delay in death time (30%) and prevented weight changes after exposure to ENU. In addition, it was found that vanillic acid protected ROS formation, lipid peroxidation mitochondrial dysfunction, and lysosomal membrane destabilization in isolated lymphocytes. These data suggest that vanillic acid exhibited significant protection against ENU-induced toxicity and carcinogenicity, which might be related to the protection of the mitochondria and lysosomes and the reduction of ROS formation and oxidative stress.
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spelling doaj.art-c20c8fd9baa84e18ac0b23232c07b7712024-04-03T04:26:40ZengElsevierToxicology Reports2214-75002024-06-0112389396Vanillic acid protects mortality and toxicity induced by N-ethyl-N-nitrosourea in mice; in vivo model of chronic lymphocytic leukemiaAhmad Salimi0Shadi Haddadi1Saleh Khezri2Bahare Asgari3Mahshad Pourgholi4Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran; Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Iran; Corresponding author at: Toxicology and Pharmacology School of Pharmacy, Ardabil University of Medical Sciences, P.O. Box: 56189-53141, Ardabil, Iran.Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran; Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, IranDepartment of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, IranDepartment of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran; Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, IranDepartment of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran; Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, IranAlkylating agents such as N-Ethyl-N-Nitrosourea (ENU) are ubiquitous within living cells and in the environment. This study designed to evaluate the chemopreventive activity of vanillic acid on ENU-induced toxicity and carcinogenesis in mice as an animal model of chronic lymphocytic leukemia (CLL). The female, Swiss albino mice were divided into three groups each with 7 mice, group I received normal saline, group II, mice received ENU at a dose of 80 mg/kg body weight i.p. to induce CLL on the 31th day of the study, and group III, the mice pretreated with vanillic acid at a dose of 20 mg/kg body weight/day, i.p. up to 30 days and received ENU. The animals were monitored for weight changes and mortality during 120 days, and then were sacrificed for isolation of lymphocytes, as target cells in CLL. Cellular parameters like reactive oxygen species (ROS) formation, malondialdehyde (MDA) production, depletion of glutathione (GSH), mitochondrial membrane potential (MMP) and lysosomal membrane integrity were studied. We found that pretreatment with vanillic acid significantly increased the survival of mice up to 57%, delay in death time (30%) and prevented weight changes after exposure to ENU. In addition, it was found that vanillic acid protected ROS formation, lipid peroxidation mitochondrial dysfunction, and lysosomal membrane destabilization in isolated lymphocytes. These data suggest that vanillic acid exhibited significant protection against ENU-induced toxicity and carcinogenicity, which might be related to the protection of the mitochondria and lysosomes and the reduction of ROS formation and oxidative stress.http://www.sciencedirect.com/science/article/pii/S2214750024000374CarcinogenesisCancer chemopreventionLeukemiaPhytochemicalsDietary
spellingShingle Ahmad Salimi
Shadi Haddadi
Saleh Khezri
Bahare Asgari
Mahshad Pourgholi
Vanillic acid protects mortality and toxicity induced by N-ethyl-N-nitrosourea in mice; in vivo model of chronic lymphocytic leukemia
Toxicology Reports
Carcinogenesis
Cancer chemoprevention
Leukemia
Phytochemicals
Dietary
title Vanillic acid protects mortality and toxicity induced by N-ethyl-N-nitrosourea in mice; in vivo model of chronic lymphocytic leukemia
title_full Vanillic acid protects mortality and toxicity induced by N-ethyl-N-nitrosourea in mice; in vivo model of chronic lymphocytic leukemia
title_fullStr Vanillic acid protects mortality and toxicity induced by N-ethyl-N-nitrosourea in mice; in vivo model of chronic lymphocytic leukemia
title_full_unstemmed Vanillic acid protects mortality and toxicity induced by N-ethyl-N-nitrosourea in mice; in vivo model of chronic lymphocytic leukemia
title_short Vanillic acid protects mortality and toxicity induced by N-ethyl-N-nitrosourea in mice; in vivo model of chronic lymphocytic leukemia
title_sort vanillic acid protects mortality and toxicity induced by n ethyl n nitrosourea in mice in vivo model of chronic lymphocytic leukemia
topic Carcinogenesis
Cancer chemoprevention
Leukemia
Phytochemicals
Dietary
url http://www.sciencedirect.com/science/article/pii/S2214750024000374
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