Recent reports described a high incidence of
nonalcoholic steatohepatitis (NASH) in patients with
obstructive sleep apnea. Accordingly, we hypothesized that recurrent and intermittent
hypoxemia plays an important role in the pathogenesis of NASH. Our objective was construction of a practical and accurate experimental model to reproduce the key features of NASH in humans. Chemical
hypoxemia through
methemoglobinemia was induced by daily
intraperitoneal injection of
sodium nitrite (40 mg/kg) for 4 weeks in rats with
fatty liver. The later was induced by 4-week feeding a
choline-deficient high-fat diet (CDHF). Besides, the normal chow diets feeding groups were prepared with in the same manner except for CDHF feeding. The animal experiment was performed in four groups; Normal control,
Hypoxemia, CDHF, and CDHF +
hypoxemia.
Nitrite was given for the later 4 weeks to each rat of
Hypoxemia and CDHF +
hypoxemia. CDHF +
hypoxemia rats were confirmed to develop histological changes that resemble those of patients with NASH, together with biochemical
liver dysfunction, while CDHF group was limited in mild steatosis, and
Hypoxemia group liver was normal. Present study established a reproducible and useful NASH model resembling the main features of NASH in humans, and showed first that recurrent and intermittent
hypoxemia aggravate
fatty liver to
steatohepatitis and
liver fibrosis.