Evaluating The Protective Effects Of Lovastatin Against Doxorubicin Induced Cardiotoxicity In Balb-C Mice.

BACKGROUND: Doxorubicin is one of the most commonly used anti-cancer drugs that treat a large number of haematological and solid malignancies. Its usage in dose and duration is nevertheless restricted by dose related organ damage, particularly cardiotoxicity. Lovastatin is a commonly prescribed drug for hypercholesterolemia and possesses remarkable antioxidant potential. Our study was aimed at evaluating and comparing its cardioprotective effect in two pre-treatment schedules against doxorubicin-induced cardiac damage. METHODS: In this lab-based randomized controlled experiment, 40 BALB/c mice were randomly grouped into five groups (n=8). Group 1 served as control whereas Group 2 was given doxorubicin intraperitoneally at a dose of 10mg/kg. Group 3 received 10mg/kg of oral lovastatin for five days. Groups 4 and 5 were administered lovastatin for five and ten consecutive days correspondingly and doxorubicin was given on 3rd and 8th experimental days of these groups. RESULTS: Doxorubicin caused a significant rise in cardiac enzymes; Creatine kinase MB (CK-MB) and Lactate Dehydrogenase (LDH) (p value ≤0.0001) whereas cardiac histological alterations were ranked as moderate. The damage was significantly attenuated by lovastatin in the ten-day study design with a p-value of ≤0.001 for both LDH and CK-MB whereas a slightly less efficient restoration was observed in the five-day design with a p value of ≤0.001 for LDH and 0.012 for CK-MB. Histological preservation in both pre-treatment schedules was in accordance with the biological markers. CONCLUSIONS: In doxorubicin-based regimens, pretreatment for at least seven days with an easily available and safe statin can effectively prevent its potentially life threatening cardiotoxicity.

Protective Effects Of Trimetazidine Against Doxorubicin-Induced Cardiotoxicity And Hepatotoxicity In Mice.

BACKGROUND: Trimetazidine (TMZ) is traditionally known for cardio protection, however various experimental studies are also evaluating its protective benefits in other tissues. Doxorubicin (DOX) is an extensively used chemotherapeutic drug but is associated with a high incidence of multi-organ damage. This study was aimed at countering DOX induced cardiac and hepatic toxicity by administering TMZ in two different study designs. METHODS: It was a laboratory based randomized controlled trial conducted on 40 BALB/c mice divided into 5 groups (n=8). In the two study designs conducted, TMZ in a dose of 10 mg/kg was given orally for five and ten consecutive days. On the third and eighth day of the respective designs, 10 mg/kg DOX was administered intraperitoneally. RESULTS: DOX induced significant elevation of four biochemical markers, namely creatine kinase MB (CKMB), lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (p-value ≤0.0001). Histological changes in heart were graded to be moderate while hepatic changes were graded as mild. Trimetazidine administration for ten days attenuated the enzyme upsurge significantly with p-value ≤0.05 for ALT and ≤0.0001 for AST, LDH and CKMB. However, five-day TMZ administration caused nonsignificant restoration in ALT and CKMB level (p-value >0.05). Hepatic and cardiac histological changes were restored accordingly in both groups. CONCLUSIONS: Treatment with TMZ for ten days, seven of which were prior to DOX administration, was concluded to be an effective strategy to counter cardiac and hepatic toxicity of DOX.