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

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

Research output: Contribution to journalArticle


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.

Original languageEnglish
Pages (from-to)803-811
Number of pages9
JournalInflammation Research
Issue number9
Publication statusPublished - 2017 Sep 1



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

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

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