TY - JOUR
T1 - The alpha-lipoic acid derivative DHLHZn
T2 - a new therapeutic agent for acute lung injury in vivo
AU - Shoji, Yoshiaki
AU - Takeuchi, Hiroya
AU - Fukuda, Kazumasa
AU - Fukunaga, Koichi
AU - Nakamura, Rieko
AU - Takahashi, Tsunehiro
AU - Wada, Norihito
AU - Kawakubo, Hirofumi
AU - Miyasho, Taku
AU - Hiratsuka, Takahiro
AU - Inomata, Masafumi
AU - Betsuyaku, Tomoko
AU - Kitagawa, Yuko
N1 - Publisher Copyright:
© 2017, Springer International Publishing.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
KW - Acute lung injury
KW - Alpha-lipoic acid
KW - Dihydrolipoyl histidinate zinc complex
KW - Nuclear factor-kappa B
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U2 - 10.1007/s00011-017-1059-x
DO - 10.1007/s00011-017-1059-x
M3 - Article
C2 - 28573312
AN - SCOPUS:85020061121
SN - 1023-3830
VL - 66
SP - 803
EP - 811
JO - Inflammation Research
JF - Inflammation Research
IS - 9
ER -