The alpha-lipoic acid derivative DHLHZn: a new therapeutic agent for acute lung injury in vivo

作者：Shoji Yoshiaki; Takeuchi Hiroya^*; Fukuda Kazumasa; Fukunaga Koichi; Nakamura Rieko; Takahashi Tsunehiro; Wada Norihito; Kawakubo Hirofumi; Miyasho Taku; Hiratsuka Takahiro; Inomata Masafumi; Betsuyaku Tomoko; Kitagawa Yuko

来源：Inflammation Research, 2017, 66(9): 803-811.

DOI：10.1007/s00011-017-1059-x

• Alpha-lipoic acid
• Dihydrolipoyl histidinate zinc complex
• Acute lung injury
• Nuclear factor-kappa B

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.

• 出版日期2017-9