Protective effect of protocatechuic acid isopropyl ester against murine models of sepsis: inhibition of TNF-alpha and nitric oxide production and augmentation of IL-10.
Antioxidants have been shown to be effective in murine models of sepsis. Protocatechuic acid has antioxidant activity. In the present study, the protective effects of protocatechuic acid and its derivatives were investigated in a mouse model of septic shock induced by lipopolysaccharide (LPS)/D-galactosamine (GalN). Pretreatment of animals with protocatechuic acid effectively suppressed LPS/GalN-induced lethality; protocatechuic acid isopropyl ester was the most effective among the various derivatives of protocatechuic acid. Protocatechuic acid isopropyl ester was also effective in protection against the high-dose LPS-induced shock. Pretreatment with protocatechuic acid isopropyl ester effectively suppressed the LPS/GalN-induced increase in plasma tumor necrosis factor (TNF)-alpha alanine aminotransferase (ALT), nitrite/nitrate levels, and hepatic malondialdehyde levels. In contrast, it markedly enhanced the LPS/GalN-induced increase in plasma interleukin (IL)-10 levels, without any changes in IL-6 plasma levels. These results suggest that protocatechuic acid isopropyl ester could be useful for the prevention of sepsis.
Yan
Ji-Jing
JJ
Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Kangwon-Do, South Korea.
Jung
Jun-Sub
JS
Hong
Young-Jin
YJ
Moon
Yoo-Sun
YS
Suh
Hong-Won
HW
Kim
Yung-Hi
YH
Yun-Choi
Hye-Sook
HS
Song
Dong-Keun
DK
D000818:Animals; D004195:Disease Models, Animal; D004952:Esters; D062385:Hydroxybenzoates / Q000494:pharmacology / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D004952:Esters; D062385:Hydroxybenzoates; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; C009091:protocatechuic acid