Abstract
Chronic oxidative stress plays a key role in the progression of nonalcoholic steatohepatitis (NASH). We examined the efficacy of antioxidative electron treatment on type 2 diabetes-induced NASH in a rat model. We established NASH model rats, induced by neonatal administration of streptozotocin and a high-fat diet, which exhibited pathologically high values of alanine aminotransferase (ALT), glucose, and malondialdehyde (MDA). The rats were exposed to electron discharge at very low energy for 4 weeks; this dose results in the reduction of Fe(3+) and glutathione disulfide in vitro. Serum ALT values were increased from baseline (8 weeks) to 125.0 ± 13 U/L at 10 weeks in the control group. In contrast, the values in the treated group did not show any increase at 10 weeks [87 ± 10 U/L (p = 0.0391)]. Hepatic MDA levels were also significantly decreased at 12 weeks (p < 0.05), but 8-hydroxy-2'-deoxyguanosine values were not statistically significant (p = 0.076). A gradual but steadily decreasing trend from initially high glucose levels was observed, though the values were not significant in 12-week-old animals (p = 0.074). However, the serum values of MDA, ALT, and glucose were well correlated. The progression of fibrosis as measured by increased serum levels of hyaluronic acid and histological examinations were not affected by the treatment in this model. Antioxidative electron treatment at very low energy attenuated the pathogenically elevated liver inflammation and oxidative stress, together with presumably impaired glucose metabolism in NASH rat model.