Acetyl-L-carnitine modulates bleomycin-induced oxidative stress and energy depletion in lung tissues.
OBJECTIVE
The usefulness of Bleomycin (BLM) as an important antineoplastic drug is usually limited to the development of dose and time-dependent interstitial pneumonitis and pulmonary fibrosis. This study has been initiated to investigate the possible protective effects of acetyl-L-carnitine (AC) against BLM-induced lung toxicity at an early stage of its development.


METHODS
A total of 40 male Sprague-Dawley rats weighing from 200-250 g each, were divided into 4 groups of 10 animals each. The first group received a daily i.p. injection of normal saline (0.5 ml/200 gm body weight) for 5 consecutive days and served as a control. Animals in the second, third and fourth groups were daily injected intraperitoneally (i.p.) with BLM (15 mg/kg body weight), AC (250 mg/kg body weight) and AC (250 mg/kg) 2 hrs before BLM (15 mg/kg) each for 5 consecutive days, respectively.


RESULTS
Treatment of rats with BLM (15 mg/kg) resulted in a significant 3.4 and 2.9 folds increase in malondialdehyde (MDA) and nitric oxide (NO) production in lung tissue, respectively and a significant 39%, 35%, 54% and 44% decrease in reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and adenosine triphosphate (ATP), respectively as compared to the control group. Treatment of rats with AC did not lead to any significant change in the mentioned biochemical parameters in the lung tissue. Administration of AC two hours before BLM attenuated BLM-induced increase in MDA and NO and the decrease in GSH, SOD, GSHPx and ATP in lung tissue.


CONCLUSIONS
The present data suggests that the protective effect of AC against BLM-induced acute lung injury could be, at least in part, due to its free radical scavenging properties with the consequent improvement in mitochondrial function and ATP production.
Sayed-Ahmed
Mohamed M
MM
The Department of Pharmacology ,National Cancer Institute,Cairo University. mmsayedahmed@hotmail.com.
Mansour
Heba H
HH
Gharib
Ola A
OA
Hafez
Hafez F
HF