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 treat...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 cancer.It is not well understood whether a combination therapy with DOX and CPS can induce hepa-totoxicity.We therefore sought to determine whether co-administration of DOX and CPS at their clini-cally relevant doses and frequency results in hepatotoxicity.Methods: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 weeks.After the treatment period,liver histology and various serum bio-markers of hepatotoxicity were assessed.Results:Co-treatment with DOX and CPS did not alter the serum levels of alanine aminotransferase(ALT),alkaline phosphatase(ALP),bilirubin,albumin,globulin,or total protein.Similarly,co-administration of DOX and CPS did not result in a noticeable change in liver histology.However,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 CPS.Conclusions: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.展开更多
基金This project was supported by Animal Health and Disease Research Grant and Auburn University Research Initiative in Cancer Grant to S.R PondugulaThis work was also supported by the USA National Institutes of Health(NIH)R00 HD082686 Grant to C.-C.J Huang.
文摘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 cancer.It is not well understood whether a combination therapy with DOX and CPS can induce hepa-totoxicity.We therefore sought to determine whether co-administration of DOX and CPS at their clini-cally relevant doses and frequency results in hepatotoxicity.Methods: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 weeks.After the treatment period,liver histology and various serum bio-markers of hepatotoxicity were assessed.Results:Co-treatment with DOX and CPS did not alter the serum levels of alanine aminotransferase(ALT),alkaline phosphatase(ALP),bilirubin,albumin,globulin,or total protein.Similarly,co-administration of DOX and CPS did not result in a noticeable change in liver histology.However,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 CPS.Conclusions: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.
