Median lethal dose (LD50) and cytotoxicity of Adriamycin in female albino mice

Rehab M Mosaad ,Amany Samir ,Hassan M Ibrahim

doi:10.7324/japs.2017.70312

Abstract

The median lethal dose of Adriamycin and its cytotoxicity in three vital organs (heart, liver and kidney) was studied. The median lethal dose (LD50) was 56.875mg/kg b.wt. . High doses of Adriamycin induced significant increases in heart tissues enzymes (lactate dehydrogenase, alkaline phosphatase and Creatine Kinase-MB isoenzyme (CKMB)). Hepatotoxicity figured in significant increment in liver function enzymes (aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) activities) and lipid profile (cholesterol and triglycerides) and significant reduction in total protein and albumin. Moreover, urea and creatinine recorded significant increases in kidney tissues after interpretoneal administration of high doses of Adriamycin (100, 90 and 80 mg/kg b.wt.).

Highlights

Adriamycin is a quinine containing anticancer and antibiotic that is used to treat many solid malignancies and lymphomas (Quiles et al, 2002)
The organs were weighed and homogenized in 10 m mol/L phosphate buffer saline (10% W/V) of PH 7.4 and centrifuged .The supernatant used for determination of lactate dehydrogenase (LDH), ALP, creatine kinase-MB isoenzyme (CKMB) in heart tissues, alanine transaminase (ALT), aspartate transaminase (AST), TP, albumin, cholesterol, triglycerides in liver tissues andurea and creatinine in kidney tissues
Among the treated animals with high doses of Adriamycin, it was found that some animals were died immediately after few seconds

Summary

INTRODUCTION

Adriamycin is a quinine containing anticancer and antibiotic that is used to treat many solid malignancies and lymphomas (Quiles et al, 2002). Adriamycin have severe toxic effects towards heart, kidney and liver so that its clinical efficacy is restricted(Quiles et al, 2002; Chae et al, 2005; Kim et al, 2006; Zahraei and Rabbani-Chadegani, 2007; Othman et al, 2008). A nephrotic syndromeis induced by a single high-dose injection of Adriamycin (ADR). Many mechanisms are consider to illustrate the cytotoxic effects of Adriamycin such as inhibition of DNA synthesis, alkylation and binding of DNA, interference of DNA strand separation and helicase activity, effects of direct membrane, cross-linking of lipid peroxidation DNA and free radical formation (Deepa and Varalakshmi, 2006). The aim of the present study isto determine the (Median lethal dose) LD50 of Adriamycin intraperitoneal injection and cytotoxicity of 80, 90, and 100 mg/kg b.wt. The aim of the present study isto determine the (Median lethal dose) LD50 of Adriamycin intraperitoneal injection and cytotoxicity of 80, 90, and 100 mg/kg b.wt. in female albino mice

MATERIAL AND METHODS

RESULTS AND DISCUSSION

CONCLUSION