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

Life Research 2024年第1期7卷 16-23页

作者： Ishrat Jahan Manju Pandey Shalini Pal bushra jabi Mohd Yaqub Khan Gaurav Kaithwas Department of Pharmaceutical Sciences Babasaheb Bhimrao Ambedkar UniversityLucknow 226025 India Institute of Pharmacy Shri Ramswaroop Memorial UniversityBarabanki 225003India School of Pharmaceutical Education&Research Jamia HamdardNew Delhi 110062India Institute of Pharmacy Azad Institute of Pharmacy and ResearchLucknow 226008India

Background:In the early metastasis of colon cancer,cancer cells detach,migrate,and infiltrate surrounding tissues,including lymph vessels and blood *** heterogeneity arises from both tumor cells and distinct *** of blood vessels,creates hypoxic regions within the tumors,fostering cancer stem cell-like properties due to reduced oxygen and nutrient *** 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 ***: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 *** 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,*** 6 weeks),followed by 5-fluorouracil and Leucovorin(25 mg/kg each on 1^(st),3^(rd),7^(th),and 10^(th) days,*** 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,*** 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).Bri

关键词： colon cancer 1,2,4-triazine derivatives oxidative stress hypoxia-induced colon carcinogenesis

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