Relationship between the eosinophilia of bronchoalveolar lavage fluid (BALF) and the severity of pulmonary fibrosis induced by bleomycin in rats.

A large number of studies have demonstrated that the presence of eosinophils in the lungs of patients with pulmonary fibrosis correlates with poor prognosis or resistance to therapy. However, direct evidence of the relationship between the influx of eosinophil and pulmonary fibrosis has not yet been described experimentally. In this article, pulmonary fibrosis was induced by different doses of bleomycin (BLM) and using different aged rats. On selected days afterwards, the lungs were lavaged and harvested for analyzing fibrosis, eosinophil influx and cytokine expression. There was a significant relationship between eosinophilia and the pulmonary fibrosis (r=0.98, p<0.01). In spite of the fact that there was no significant increase in hydroxyproline of the lung, eosinophil influxes of bronchoalveolar lavage fluid (BALF) was maximal 7 d after BLM administration. Moreover, there were similar patterns among transforming growth factor beta (TGF)-beta(1), hepatocyte growth factor (HGF) and eosinophil influx of BALF in that they were dependent on dose of BLM and age. These findings, taken together, have suggested the causal correlation of eosinophilia during the early stage with subsequent pulmonary fibrosis. The possible role of eosinophils in the pathogenesis of pulmonary fibrosis might contribute to not only TGF-beta(1) but also HGF production.

Effect of Sho-saiko-to extract on hepatic inflammation and fibrosis in dimethylnitrosamine induced liver injury rats.

Sho-saiko-to extract, a Chinese herbal medicine, is widely used for treatment of chronic hepatitis in Japan. However, it is not clear what conditions Sho-saiko-to extract improves hepatic inflammation and fibrosis. We therefore induced various stages of liver injury in model rats and administered Sho-saiko-to extract. We then evaluated the liver inflammation and liver fibrosis-improving effects of Sho-saiko-to extract. The liver injury model rats were produced by administration of various doses of dimethylnitrosamine (DMN) and Sho-saiko-to extract was administered to these rats. Then the liver inflammation and fibrosis-improving effects of Sho-saiko-to extract were evaluated according to L-asparate aminotransferase (AST), L-alanine aminotransferase (ALT), liver retinoid levels, levels of hydroxyproline, Transforming Growth Factor-beta (TGF-beta), and the liver fibrosis area. These indicators depended on the total doses of DMN. The ability of Sho-saiko-to extract to improve liver inflammation and fibrosis was limited to the following levels of the respective parameters: AST levels (234-264 U/l), ALT levels (208-232 U/l), TGF-beta levels (1102-1265 pg/g liver tissue), hydroxyproline levels (633-719 nmol/g liver tissue), and liver fibrosis area (9.7-10.6 times for normal rat). These findings suggested that Sho-saiko-to extract is effective in the treatment of liver inflammation and fibrosis up to a certain degree of severity, but it produces no improvement in more severe cases.

Effects of extract derived from Eriobotrya japonica on liver function improvement in rats.

Eriobotrya japonica is considered a medicinal plant, and its leaves (Eriobotrya folia) have been used to treat skin diseases, as well as to relieve inflammation, pain, coughing, and sputa. In our evaluation of the pharmacological efficacy of the seed extracts, constituents of the seeds were found to contain the unsaturated fatty acids linolenic and linoleic acids and the sterol beta-sitosterol in the 70% EtOH and the MeOH extracts. The seed extracts were orally administered to rats with dimethylnitrosamine-induced hepatopathy, and blood L-asparate aminotransferase (AST) and L-alanine aminotransferase (ALT) levels, liver retinoid level, and hydroxyproline level were measured. Liver fibrosis rates calculated after Azan-Mallory staining and evaluation of the liver function-improving effects of extracts were showed that AST, ALT, and hydroxyproline levels and liver fibrosis rates were significantly lower, and retinoid levels were significantly higher in hepatopathic rats treated with 70% EtOH and MeOH extracts of the seed than in water-treated control rats. This suggests that the positive effect on liver function of the extracts varies depending on the extracting solvent used. 70% EtOH and MeOH extract of the seeds inhibited the development of liver fibrosis in hepatopathic rats, thus exhibiting potent improvement. The unsaturated linolenic and linoleic acids and the sterol beta-sitosterol contained in these extracts may also contribute to the improvement of liver function.