In Vivo Study of Radioprotective Effect of NO-Synthase Inhibitors and Acetyl-L-Carnitine

Abstract

This study investigated the protective effect of two nitric oxide synthase inhibitors Nω-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg i.p.) and aminoguanidine (AG, 400 mg/kg i.p.), and an antioxidant acetyl-L-carnitine (ALC, 250 mg/kg i.p., once daily for five days) against radiation-induced damage in Wistar rats. Blood samples were collected 6 h after whole-body irradiation with 8 Gy. Plasma concentrations of nitrite+nitrate (NOx) and malondialdehyde (MDA) were measured by high-performance liquid chromatography. A single injection of L-NAME one hour before exposure effectively prevented the radiation-induced elevation of plasma NOx and it reduced 2.6-fold the risk for death during the subsequent 30-day period. Pretreatment with ALC prevented the radiation-induced increase in plasma MDA and it had similar effect on mortality as L-NAME did. Presumably due to its short half-life, the partially iNOS-selective inhibitor and antioxidant AG given in a single dose before exposure did not attenuate MDA and NOx and it failed to significantly improve the 30-day survival. In conclusion, pretreatment with both the nonspecific NOS inhibitor L-NAME and the antioxidant ALC markedly reduce mortality to radiation sickness in rats. The radioprotective effect may be directly related to effective attenuation of the radiation-induced elevation of NO production by L-NAME and of oxidative stress by ALC.

Effects of l-Carnitine on the Follicle-Stimulating Hormone, Luteinizing Hormone, Testosterone, and Testicular Tissue Oxidative Stress Levels in Streptozotocin-Induced Diabetic Rats

“…Moreover, studying the antioxidant role of LC on reduction of radiotherapy-induced complications in various tissues such as brain, liver, and retina showed that using LC before or after radiotherapy significantly decreased the level of MDA and ROS and improved GSH and CAT levels. [59][60][61] Our results revealed that CAT significantly increased in diabetic groups treated with LC versus untreated diabetic group. Oxidation of biological molecules can be induced by hydroxyl (OH À_ c ) radicals generated by hydrogen peroxide (H 2 O 2 ).…”

Carnitine Enigma: From Antioxidant Action to Vitagene Regulation. Part 1. Absorption, Metabolism, and Antioxidant Activities

“…Furthermore, pre-treatment with ALC (250 mg/kg, i.p.) of rats prevented the radiation-induced increase in plasma MDA [177]. From the data presented above it is clear that LC and ALC have antioxidant protective effect against oxidative stress caused by irradiation.…”

Comparing effects of L-carnitine and sildenafil citrate on histopathologic recovery from sciatic nerve crush injury in female albino rats

“…It was found that L-carnitine had an effect on the recovery of sciatic nerve function as well as enhancing nerve regeneration and suppressing injury-induced degeneration in the nerve axon and its myelin sheath. Wilson et al [68] and Babicova et al [7] explained that L-carnitine blocked the cell death pathway at the mitochondrial level by limiting reactive oxygen species synthesis in addition to reducing the nitric oxide and nitric oxide synthase levels.…”