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

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.

COVID-19 induced renal injury differs from that in other viral-infections

Background:Kidney injuries caused by several viral diseases have been reported worldwide among all age groups,races,and genders.Of particular importance is coronavirus disease 2019(COVID-19),and its prevalence in communities infecting all patient populations with symptoms ranging from asymptomatic to severe,including complications and mortality.Methods:Data were acquired from PubMed,Scopus,Google Scholar,Centers for Disease Prevention and Control(CDC),and Lexi-Comp using the following search terms:“COVID-19 and renal pathology,”“COVID-19 induced kidney disease,”“Viral infection induced kidney disease,”and“Viral infection induced renal damage.”Titles and abstracts were manually analyzed as per the exclusion and inclusion criteria of relevant articles;relevance of articles included studies on the pathology of a specific viral infection and the impact of the virus on the adult renal system.Results:The mechanisms for renal disease due to COVID-19 include direct renal tubular injury,cytokine storm,inflammation,thrombosis vs.acute tubular necrosis,thrombotic events,and direct renal injury.Although some mechanisms behind renal dysfunction among the studied viral infections are similar,the prevalence rates of kidney injury or damage differ.This might be described by recommended prophylactic and therapeutic approaches that can alter the viral infection characteristics and possibly the impact a particular organ system.Conclusion:The patient population at risk was old in age and had a high body mass index.The mechanisms associated with renal dysfunction are similar,including direct renal injury through angiotensin converting enzyme 2(ACE2)entry,inflammation,and thrombosis.The renal pathology of coronaviruses that differs from that of other prevalent viral infections is the activation of cytokine storm,which causes elevations of a greater number and different kinds of cytokines than other viral infections.