Yoshiaki Shoji1, Hiroya Takeuchi2,3, Kazumasa Fukuda1, Koichi Fukunaga4, Rieko Nakamura1, Tsunehiro Takahashi1, Norihito Wada1, Hirofumi Kawakubo1, Taku Miyasho5, Takahiro Hiratsuka6, Masafumi Inomata6, Tomoko Betsuyaku4, Yuko Kitagawa1. 1. Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan. 2. Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan. htakeuch@a6.keio.jp. 3. Department of Surgery, School of Medicine, Hamamatsu University, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan. htakeuch@a6.keio.jp. 4. Division of Pulmonary Medicine, Department of Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan. 5. Department of Veterinary Science, School of Veterinary Medicine, Rakuno Gakuen University, 582, Bunkyo-dai, Midori-machi, Ebetsu, Hokkaido, 069-8501, Japan. 6. Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine, Oita University, 1-1, Idaigaoka, Hazama-cho, Yufu-Shi, Oita Prefecture, 879-5593, Japan.
Abstract
OBJECTIVE AND DESIGN: An animal experiment was performed to demonstrate the anti-inflammatory effects of an alpha-lipoic acid (ALA) derivative, dihydrolipoyl histidinate zinc complex (DHLHZn) for acute lung injury (ALI) and to investigate the mechanism of action. MATERIAL: Rats were randomly divided into three experimental groups: control group (n = 17), DHLHZn(-) group (n = 11, ALI model rats), and DHLHZn(+) group (n = 12, ALI model rats treated by DHLHZn). TREATMENT: Lipopolysaccharides (LPS, 10 mg/kg) were administered intratracheally in the DHLHZn(-) group and the DHLHZn(+) group. For the DHLHZn(+) group, DHLHZn (100 mg/kg) was administered intraperitoneally 2 h prior to LPS administration. METHODS: Four hours after LPS administration, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The findings were analyzed using the Mann-Whitney U test. RESULTS: Total number of cells, number of neutrophils and lymphocytes, levels of various inflammatory cytokines, and NF-kB p65 concentration of BALF were significantly lower in the DHLHZn(+) group than in the DHLHZn(-) group (p < 0.05). ALI pathology scores were significantly lower in the DHLHZn(+) group than in the DHLHZn(-) group (p < 0.001). CONCLUSIONS: Anti-inflammatory effects of DHLHZn for ALI were demonstrated by BALF and histopathological findings. The mechanism of action of DHLHZn was considered to be via inhibition of the NF-kB signaling pathway. DHLHZn is thus suggested to be a new prophylactic agent for ALI.
OBJECTIVE AND DESIGN: An animal experiment was performed to demonstrate the anti-inflammatory effects of an alpha-lipoic acid (ALA) derivative, dihydrolipoyl histidinate zinc complex (DHLHZn) for acute lung injury (ALI) and to investigate the mechanism of action. MATERIAL: Rats were randomly divided into three experimental groups: control group (n = 17), DHLHZn(-) group (n = 11, ALI model rats), and DHLHZn(+) group (n = 12, ALI model rats treated by DHLHZn). TREATMENT: Lipopolysaccharides (LPS, 10 mg/kg) were administered intratracheally in the DHLHZn(-) group and the DHLHZn(+) group. For the DHLHZn(+) group, DHLHZn (100 mg/kg) was administered intraperitoneally 2 h prior to LPS administration. METHODS: Four hours after LPS administration, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The findings were analyzed using the Mann-Whitney U test. RESULTS: Total number of cells, number of neutrophils and lymphocytes, levels of various inflammatory cytokines, and NF-kB p65 concentration of BALF were significantly lower in the DHLHZn(+) group than in the DHLHZn(-) group (p < 0.05). ALI pathology scores were significantly lower in the DHLHZn(+) group than in the DHLHZn(-) group (p < 0.001). CONCLUSIONS: Anti-inflammatory effects of DHLHZn for ALI were demonstrated by BALF and histopathological findings. The mechanism of action of DHLHZn was considered to be via inhibition of the NF-kB signaling pathway. DHLHZn is thus suggested to be a new prophylactic agent for ALI.
Authors: Sang Heon Suh; Ko Eun Lee; In Jin Kim; Ok Kim; Chang Seong Kim; Joon Seok Choi; Hoon-In Choi; Eun Hui Bae; Seong Kwon Ma; Jong Un Lee; Soo Wan Kim Journal: Clin Exp Nephrol Date: 2014-03-19 Impact factor: 2.801