Functional food development to target NASH: Spirulina intervening in both hits

Recent reports described 7-fold incidence of nonalcoholic steatohepatitis (NASH) in obese patients with obstructive sleep apnea (OSA). As the pathogenesis of NASH, the 'two-hit' theory is widely accepted. The first hit is the accumulation of fatty acids in the liver to cause steatosis. The secondary stress, including cytokines, oxidative stress and activation of hepatic stellate cells seem to play a role in progression of steatohepatitis. Ischemic hepatitis during OSA has been reported. Accordingly, we hypothesized that recurrent and intermittent hypoxemia is similar to the condition of warm ischemia followed by re-oxygenation, which induces oxidative stress postulated as one of the "second hits" in the "two-hit theory". By exposing to recurrent and intermittent hypoxemia through methemoglobinemia, for fatty liver animals, that reproduced the similar condition to OSA, we established a practical and accurate experimental model of NASH [INPADOC: PCT/JP2007/52477] to reproduce the key features of NASH patients, with necro-inflammatory activity, nonspecific inflammatory infiltrates, hepatocyte ballooning, occasional fibrosis, and besides with great amounts of reactive oxygen species derivation from the liver mitochondria metabolism. In our morbid model, NASH seemed to be aggravated by the cross talk between oxidative stress and inflammation. Our results of antioxidant food interventions appeared to have considerable potential for attenuating NASH progression from controlling oxidative stress and inflammation. Besides these, notably, spirulina platensis exerted remarkable effect to reduce NASH risk also by improving hepatic steatosis. Thus, it is sure strategy to target NASH to attenuate both hits in the "two-hit theory".