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.