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A clinically relevant combination treatment with doxorubicin and cyclophosphamide does not induce hepatotoxicity in C57BL/6J mice

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Liver research 2021年第4期5卷 239-242页

作者： satyanarayana r pondugula Julia M Salamat Kodye L Abbott Patrick C Flannery Mohammed Majrashi Mohammed Almaghrabi Manoj Govindarajulu Sindhu ramesh Maninder Sandey Suneel K Onterue Chen-Che J Huang Yoshimi Iwaki Kristina Gill Natasha Narayanan Edwin McElroy Darshini Desai rishi Nadar Timothy Moore Muralikrishnan Dhanasekaran Department of Anatomy Physiology and PharmacologyCollege of Veterinary MedicineAuburn UniversityAuburnALUSA Department of Pharmacology Faculty of MedicineUniversity of JeddahJeddahSaudi Arabia Department of Drug Discovery and Development Harrison School of PharmacyAuburn UniversityAuburnALUSA Department of Pathobiology College of Veterinary MedicineAuburn UniversityAuburnALUSA Animal Biochemistry Division National Dairy Research InstituteICAR-National Dairy Research InstituteKarnalHaryanaIndia Department of Clinical Science College of Veterinary MedicineAuburn UniversityAuburnALUSA

Background and aims:Chronic exposure to chemotherapeutics can lead to severe adverse events including hepatotoxicity.A combination chemotherapy regimen of doxorubicin(DOX)and cyclophos-phamide(CPS)is employed in treatment of several cancers such as leukemia,lymphoma,and breast *** is not well understood whether a combination therapy with DOX and CPS can induce *** therefore sought to determine whether co-administration of DOX and CPS at their clini-cally relevant doses and frequency results in ***:Male C57BL/6J mice received one intraperitoneal injection of saline or DOX-2 mg/kg and CPS-50 mg/kg once a week for 4 *** the treatment period,liver histology and various serum bio-markers of hepatotoxicity were ***:Co-treatment with DOX and CPS did not alter the serum levels of alanine aminotransferase(ALT),alkaline phosphatase(ALP),bilirubin,albumin,globulin,or total ***,co-administration of DOX and CPS did not result in a noticeable change in liver ***,it was notable that the concomitant treatment with DOX and CPS resulted in a significant increase in serum levels of aspartate aminotransferase(AST).Elevated serum AST levels were also associated with increased serum creatinine kinase(CK)levels,suggesting that the elevated serum AST levels are likely due to muscle injury following the co-administration of DOX and ***:Taken together,our results,for the first time,suggest that co-administration of DOX and CPS,at their clinically relevant doses and frequency does not induce a significant hepatotoxicity in the mice.

关键词： Cyclophosphamide(CPS) Doxorubicin(DOX) Hepatotoxicity Liver injury Muscle injury

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