Abstract
We have searched for the novel physiological role of vitamin C (ascorbic acid, AsA) using ODS rat, which is a rat mutant unable to synthesize AsA. We found that ODS rats fed an AsA-free diet had increased hepatic expression and the serum concentration of acute phase proteins (APPs) including C-reactive protein. This finding suggested that AsA deficiency caused hepatic inflammatory changes, because APPs are known as the inflammatory biomarker. Subsequently, we showed that AsA deficiency stimulated the hepatic activation (phosphorylation) of signal transducer and activator of transcription 3 (STAT3), which is a transcription factor inducing the expression of APPs. STAT3 is activated by proinflammatory cytokines such as interleukin-6 (IL-6). Recently, we demonstrated that AsA deficiency elevated IL-6 mRNA level in the intestine and the concentration of IL-6 in portal blood. These results suggest that IL-6 produced in the intestine as a result of AsA deficiency is recruited to the liver via the portal vein, contributing to hepatic STAT3 activation and the elevated expression of APPs. Furthermore, we tried to verify the anti-inflammatory effect of AsA against lipopolysaccharide(LPS)-induced sepsis using ODS rats. LPS was intraperitoneally injected to ODS rats fed an AsA-free diet, a diet supplemented with 300 mg/kg AsA, or a diet supplemented with 3,000 mg/kg AsA. As a result, the dietary intake of AsA remarkably improved the survival rates of ODS rats with sepsis induced by LPS in a dose-dependent manner and suppressed tissue inflammatory damage in the septic ODS rats.
