J Korean Pediatr Soc.  1998 Jun;41(6):760-768.

The Role of Apoptosis in Adriamycin Induced Cardiotoxicity and Preventive Effect of L-carnitine in Rat

• Hong YM
• Kim SS

Abstract

PURPOSE: Adriamycin is very important in cancer chemotherapy. Unfortunately, the drug shows cumulative dose dependent cardiotoxicity. The precise mechanism of this remains unclear. It has been shown that adriamycin induces programmed cell death or apoptosis in many tissues. But the role of apoptosis in adriamycin induced cardiotoxicity is uncertain.
METHODS
Sprague-Dawley rats were divided into four groups of ten animals each. All four groups were given intraperitoneal injections for 4 weeks. The first group was given 0.9% normal saline. The second group was injected twice a week with adriamycin (5mg/kg), the third group with adriamycin (5mg/kg) and L-carnitine (200mg/kg). The fourth group was injected with only L-carnitine. Cell morphology was evaluated by light and electron-microscopy. Apoptosis was detected by labelling nicked ends of DNA fragments using Tunnel staining kit.
RESULTS
There was no difference of the left ventricular internal dimension and ventricular septal thickness among the four groups. Apoptosis was significantly increased in the adriamycin treated group compared to the control group (P<0.05). Addition of L-carnitine to adriamycin induced apoptosis compared significantly to apoptosis in the adriamycin only group (P<0.05).
CONCLUSION
Apoptosis may play an important role in adriamycin induced cardiomyopathy. L- carnitine reduces adriamycin induced apoptosis.

Keyword

Adriamycin; Cardiotoxicity; L-canitine

MeSH Terms

Animals
Apoptosis*
Cardiomyopathies
Carnitine*
Cell Death
DNA
Doxorubicin*
Drug Therapy
Injections, Intraperitoneal
Rats*
Rats, Sprague-Dawley
Carnitine
DNA
Doxorubicin