For elucidation of the taxonomic status of the Japanese Fasciola species, whole mitochondrial DNA of Fasciola hepatica from Australia, F. gigantica from Malaysia, and Fasciola sp. from Japan was digested with three four-base-cutting endonucleases: HinfI, MspI, and RsaI. The resulting digestion patterns showed that for each enzyme there were some bands specific for each geographical isolate and that the Japanese Fasciola sp. shared more bands with F. gigantica than with F. hepatica. Nucleotide sequences of two regions, the second internal transcribed spacer (ITS2) of the nuclear ribosomal RNA cluster and mitochondrial cytochrome c oxidase subunit I (COI), were also compared among them. The ITS2 sequence was highly conserved among the three isolates. F. gigantica and the Japanese Fasciola sp. were identical, but they differed from the Australian F. hepatica at six sites, one of which was a deletion. The COI sequence was less conserved but implied a similar relationship between the isolates. There seems no reason to regard the Japanese Fasciola sp. as anything other than a strain of F. gigantica.
Although several characteristic features existed, the outcome as well as prognostic factors of Japanese PSC patients appeared to be similar to those from the United States and European countries. In contrast, the incidence of CCA in PSC appeared to be lower in Japan.
Doxorubicin, a potent anticancer drug, is effective against a wide range of human neoplasms. However, the clinical uses of doxorubicin have been limited due to its serious cardiotoxic effects, which are likely the result of generation of free radicals and lipid peroxidation. S-Allylcysteine (SAC), an organosulfur compound purified from garlic, has been reported to have antioxidant and radical scavenging effects. Thus, we examined the effect of SAC on doxorubicin toxicity in mice. Severe doxorubicin toxicity was induced in mice by a single intraperitoneal injection (15 mg/kg body weight). SAC (30 mg/kg) was injected intraperitoneally daily for 5 days, starting two days prior to the administration of doxorubicin. Body weight was measured every alternate day. A measurement of serum creatine phosphokinase (CPK) and a histopathological analysis of the heart and liver was performed 6 days after the administration of doxorubicin. Death of any of the animals was recorded during the observation period. Doxorubicin injection induced a mortality rate of 58%, with SAC treatment reducing the doxorubicin-induced mortality rate to 30%. The severe body weight loss caused by doxorubicin (13%) was also significantly attenuated by SAC treatment (9%). Although an elevation of the level of serum CPK was observed following doxorubicin injection (5472 +/- 570 i.u./L), treatment with SAC significantly reduced the level of CPK (1923 +/- 635 i.u./L). Histological analysis demonstrated that heart and liver damage was significantly less severe in SAC treated mice than in mice receiving only doxorubicin. These results suggest that SAC research may ultimately lead to a resolution of the adverse effects of doxorubicin treatment in cancer chemotherapy.
To examine the effects of Sho-saiko-to extract on liver regeneration, Sho-saiko-to extract (0.75%, 1.5% or 3%) was administered to 70% partial hepatectomized rats with dimethylnitrosamine-induced liver-injury. S phase cell number, liver retinoid levels, hepatocyte growth factor (HGF) and transforming growth factor-beta (TGF-beta) levels in each intraorgan were measured as indicators of liver regeneration. Three to seven days after hepatectomy, HGF and TGF-beta levels of the liver and spleen of the Sho-saiko-to extract groups were significantly different from the levels of the ordinary food group (P < 0.05-0.1). HGF levels in the Sho-saiko-to extract groups were approximately 1.3-1.8 times higher in the liver and approximately 1.8-2.1 times higher in the spleen compared with the levels found in the ordinary food group. TGF-beta levels in the Sho-saiko-to extract groups were approximately 0.38-0.47 times the level in the liver and 0.58-0.77 times the level in the spleen of the ordinary food group. There was no difference in HGF and TGF-beta levels of the kidney and lung between the Sho-saiko-to extract group and the ordinary food group. There was a significant and positive correlation between HGF level and S phase cell number in the liver (r = 0.826, P < 0.01). There was a significant and negative correlation between TGF-beta level and the retinoid level in the liver (r = -0.696, P < 0.01). In addition, the levels of the active constituents of Sho-saiko-to extract (glycyrrhetic acid, baicalin and baicalein) showed high values in the liver and spleen of partial hepatectomized rats, and increased from the third day after partial hepatectomy. These results show that Sho-saiko-to extract induces liver regeneration by increasing the production of HGF and suppressing the production of TGF-beta in the liver and spleen of partial hepatectomized rats. It was considered that the increase in the Sho-saiko-to extract active constituent levels in the liver and spleen greatly influences this action.
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