Influence of nuclear factor-κB inhibition on endothelin-1 induced lung edema and oxidative stress in rats.

The aim of the present study is to determine the effects of the BAY 11-7082, a nuclear factor-kappaB (NF-κB) inhibitor, on endothelin-1 (ET-1) induced lung edema, the level of reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α) in the lungs. Experiments were carried out on adult male Wistar-Kyoto rats. The animals were divided into 4 groups: Group I: saline-treated control; Group II: saline followed by ET-1 (12.5 µg/kg b.w., i.v.); Group III: BAY 11-7082 (10 mg/kg b.w., i.v.) administered one hour before saline; Group IV: BAY 11-7082 (10 mg/kg b.w., i.v.) administered 1 hour before ET-1 (12.5 µg/kg b.w., i.v.). Injection of ET-1 alone showed a significant (P<0.001) increase in thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H(2)O(2)) level as well as a decrease (P<0.01) in GSH level and GSH/GSSG ratio (P<0.02). BAY 11-7082 significantly decreased TBARS (P<0.01) and H(2)O(2) (P<0.05) level as well as improved the redox status (P<0.02) in the lungs. BAY 11-7082 also prevented ET-1 induced lung edema (P<0.05). The concentration of TNF-α (P<0.02) and p65 subunit of NF-κB signaling compound (P<0.001) was increased in the presence of ET-1, while BAY 11-7082 decreased both TNF-α level (P<0.05) and p65 subunit concentration (P<0.01). Our results indicate that BAY 11-7082 plays a protective role in ET-1 induced oxidative lung injury. It successfully prevents lung edema as well as ROS and TNF-α overproduction. Our results also highlight the important role of the NF-κB pathway in ET-1 induced lung injury and ROS overproduction.

Effects of extremely low frequency magnetic field on the parameters of oxidative stress in heart.

Increasing production of free radicals in organisms is one of the putative mechanisms by which a extremely low frequency magnetic field (ELF-MF) may affect biological systems. The present study was designated to assess if ELF-MF applied in the magnetotherapy, affects generation of reactive oxygen species (ROS) in heart tissue and antioxidant capacity of plasma according to its working time. The experiments were performed on 3 groups of animals: group I - control; group II - exposed to 40 Hz, 7 mT, 30 min/day for 14 days (this field is commonly applied in magnetotherapy); group III - exposed to 40 Hz, 7 mT, 60 min/day for 14 days. Control rats were housed in a separate room without exposure to ELF-MF. Immediately after the last exposure, blood was taken from the tail vein and hearts were removed under anesthesia. The effect of the exposure to ELF-MF on oxidative stress was assessed on the basis of the measurements of thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H(2)O(2)), total free sulphydryl groups (-SH groups) and reduced glutathione (GSH) concentrations in heart homogenates. The total antioxidant capacity of plasma was measured using ferric reducing ability method (FRAP). Exposure to ELF-MF (40 Hz, 7 mT, 30 min/day for 2 weeks) did not significantly alter tissue TBARS, H(2)O(2), total free -SH groups, reduced glutathione (GSH) and total antioxidant capacity of plasma. By contrast, ELF-MF with the same frequency and induction but used for 60 min/day for 14 days caused significant increase in TBARS and H(2)O(2) concentration (P<0.01) and decrease in the concentration of GSH (P<0.05) and total free -SH groups in heart homogenates. Moreover, exposure of rats to ELF-MF (40 Hz, 7 mT, 60 min/day for 2 weeks) resulted in the decrease of plasma antioxidant capacity. Our results indicate that effects of ELF-MF on ROS generation in the heart tissue and antioxidant capacity of plasma depend on its working time.

Effect of alpha-lipoic acid on LPS-induced oxidative stress in the heart.

Lipopolysaccharide (LPS) is a gram-negative bacterial endotoxin and a major factor that contributes to multiple organ failure, including heart injury. Myocardial dysfunction in septic shock depends on the presence of proinflammatory cytokines and reactive oxygen/nitrogen species. In this study, the effect of early administration of an antioxidant, alpha-lipoic acid (LA) on lipid peroxidation, hydrogen peroxide (H(2)O(2)), sulphydryl groups (-SH groups) and total protein concentration and the glutathione redox system was evaluated in the heart homogenates obtained from LPS-induced endotoxic shock rats (Escherichia coli 026:B6, 30 mg/kg, i.v.). The animals were treated intravenously with saline or LA (60 mg/kg or 100 mg/kg i.v.) 30 min after LPS injection. Five hours after LPS, LA or saline administration, the animals were sacrificed and their hearts were isolated for measurements. Injection of LPS alone resulted in the development of shock and oxidative stress that was indicated by a significant increase in thiobarbituric acid reactive substances (TBARS) and H(2)O(2) concentrations, a decrease in concentration of -SH groups and reduced glutathione, and by decrease in glutathione redox ratio reduced glutathione (GSH)/oxidized glutathione (GSSG) in the heart. Administration of LA after the LPS challenge resulted in an increase in the sulfhydryl group content and a decrease in TBARS and H(2)O(2) concentrations in the heart as compared with the LPS group. In addition, the treatment of LA after LPS challenge significantly decreased the level of GSSG, increased the level of GSH in heart homogenates resulting in an increase of the GSH/GSSG ratio compared with the LPS group. There was no difference in oxidative stress reduction between 60 mg/kg and 100 mg/kg doses. These results indicate that early administration of LA is highly effective in dampening endotoxin-induced oxidative stress in the heart and in improving the glutathione redox system. This study supports the idea that alpha-LA is a free radical scavenger and a potent antioxidant.