Effect of acetyl-L-carnitine pretreatment on radiation pneumonitis and L-arginine-NO metabolic pathway
Abstract
Purpose: The purpose of our study is to examine the effect of acetyl-L-carnitine (ALC) pretreatment on radiation pneumonitis and L-arginine-nitric oxide (NO) metabolic pathway after local chest irradiation. Materials and methods: Female Wistar rats were pretreated with either phosphate buffer saline or ALC and locally irradiated by a dose of 15 Gy onto the chest.
Samples were collected 7 weeks after irradiation. Exhaled NO was monitored using chemiluminiscence method.
In plasma and bronchoalveolar lavage (BAL) fluid, nitrite/nitrate (NOx) and malondialdehyde were measured by high-performance liquid chromatography. Total protein concentration was assayed colorimetrically.
In lungs, inducible and endothelial nitric oxide synthase (iNOS, eNOS), arginase (Arg) I and II, cationic amino acid transporter (CAT) 1, 2 and 3 relative mRNA expression were measured by RT-PCR. Expression of Arg I and II was also evaluated by Western blot.
Histochemical analysis was used to measure air/tissue ratio and neutrophil infiltration. Results: ALC pretreatment increased survival rate of irradiated rats.
It also decreased NOx concentration in BAL, while in lungs, we observed increased air/tissue ratio, reduced neutrophil infiltration, decreased CAT 1 and CAT 3 mRNA expression, and reduced Arg I and Arg II expression. Conclusions: ALC pretreatment improves clinical prognosis and seems to reduce intensity of post-radiation changes on a molecular and microscopic level.