Prevention and treatment of hypoxia-induced colorectal cancer damage in albino Wister rats  

作　　者：Ishrat Jahan Manju Pandey Shalini Pal Bushra Jabi Mohd Yaqub Khan Gaurav Kaithwas 

机构地区：[1]Department of Pharmaceutical Sciences,Babasaheb Bhimrao Ambedkar University,Lucknow 226025 India [2]Institute of Pharmacy,Shri Ramswaroop Memorial University,Barabanki 225003,India [3]School of Pharmaceutical Education&Research,Jamia Hamdard,New Delhi 110062,India [4]Institute of Pharmacy,Azad Institute of Pharmacy and Research,Lucknow 226008,India

出　　处：《Life Research》2024年第1期16-23,共8页TMR生命研究

基　　金：C.Karthikeyan,Indira Gandhi National Tribal University,Lalpur,Amarkantak,Anuppur,Madhya Pradesh,484887,India,for providing the gift sample of 1,2,4-triazine derivatives used for the study.

摘　　要：Background:In the early metastasis of colon cancer,cancer cells detach,migrate,and infiltrate surrounding tissues,including lymph vessels and blood vessels.Tumor heterogeneity arises from both tumor cells and distinct microenvironments.Maldistribution of blood vessels,creates hypoxic regions within the tumors,fostering cancer stem cell-like properties due to reduced oxygen and nutrient supply.Under hypoxia,tumor cells shift to a glycolytic pathway,producing more lactic acid that acidifies the microenvironment and leads to unstable heart rate variability(HRV)factors,weight disparity,and a higher incidence of aberrant crypt foci(ACF).These hypoxic-induced parameters promote cancer cell invasion,increase radiation resistance,and facilitate cancer cell migration.Methods:In this study,we induced hypoxia-preneoplastic colon damage in albino Wister rats by administrating 1,2-dimethyl hydrazine(DMH).After successfully creating a hypoxic environment in albino Wister rats,resulting in preneoplastic colon damage,we randomly allocated Wistar albino rats into seven groups,each containing 8 animals,and conducted a 6-week study.Group 1-Normal control(administered 1 mM EDTA+saline,2 ml/kg/day,p.o.);group 2-Toxic control(administered DMH,30 mg/kg/week,s.c.);group 3-Standard treatment(DMH,30 mg/kg/week,s.c.for 6 weeks),followed by 5-fluorouracil and Leucovorin(25 mg/kg each on 1^(st),3^(rd),7^(th),and 10^(th) days,i.p.after 6 weeks administration of DMH);group 4-Low dose of P1(DMH,30 mg/kg/week,s.c.+P1,2 mg/kg,i.v.,weekly for 3 weeks);group 5-High dose P1(DMH,30 mg/kg/week,s.c.+P1,4 mg/kg,i.v.,weekly for 3 weeks),group 6-Low dose of P2(DMH,30 mg/kg/week,s.c.,+P2,2 mg/kg,i.v.,weekly for 3 weeks),group 7-High dose of P2(DMH,30 mg/kg/week,s.c.,+P2,4 mg/kg,i.v.weekly for 3 weeks).Results:DMH-treated rats exhibited alterations in HRV factors,weight disparity,elevated gastric pH,increased total acidity,a higher incidence of ACF,and changes in antioxidant markers(TBARs,SOD,catalase,GSH).Brightfield microscopy at 40x magnification reveale

关 键 词：colon cancer 1 2 4-triazine derivatives oxidative stress hypoxia-induced colon carcinogenesis 

分 类 号：R73[医药卫生—肿瘤]