A water-soluble extract from cultured medium of Ganoderma lucidum (Reishi) mycelia attenuates the small intestinal injury induced by anti-cancer drugs.

The present study investigated whether a water-soluble extract from the culture medium of Ganoderma lucidum (Reishi) mycelia (MAK) is able to protect the small intestine against damage induced by anti-cancer drugs. Six-week-old male B6C3F1/Crlj mice were fed a basal diet (MF) alone or with various doses of MAK or Agarics blazei Murrill (AGA) beginning one week before treatment with the anti-cancer drugs. Mice were sacrificed 3.5 days after injection of the anti-cancer drug, the small intestine was removed and tissue specimens were examined for the regeneration of small intestinal crypts. In experiment 1, the number of regenerative crypts after the administration of 5-fluorouracil (5FU) intravenously (250 mg/kg) or intraperitoneally (250 or 500 mg/kg) was compared after treatment with MAK or AGA. MAK protected against 5FU-induced small intestinal injury whereas AGA did not. In experiment 2, we investigated the protective effect of MAK against small intestinal injury induced by the anti-cancer drugs: UFT (tegafur with uracil; 1,000 mg/kg, orally), cisplatin (CDDP; 12.5 and 25 mg/kg, intraperitoneally), cyclophosphamide (CPA; 250 mg/kg, orally) and gefitinib (Iressa; 2,000 and 4,000 mg/kg, orally). UFT and CDDP decreased the number of regenerative crypts, but treatment with MAK attenuated the extent of UFT- or CDDP-induced small intestinal injury. CPA or Iressa plus MAK up-regulated crypt regeneration. The present results indicate that MAK ameliorates the small intestinal injury caused by several anti-cancer drugs, suggesting that MAK is a potential preventive agent against this common adverse effect of chemotherapy.

Differentiation of a hepatic phenotype after heterotropic transplantation of heart, kidney, brain, and skin tissues into liver in F344 rats.

While organ-specific stem cells with roles in tissue injury repair have been documented, their pathogenic significance in diseases and the factors potentially responsible for their activation remain largely unclear. In the present study, heart, kidney, brain, and skin samples from F344 transgenic rats carrying the GFP gene were transplanted into normal F344 rat liver one day after an intraperitoneal injection (i.p.) of carbon tetrachloride (CCl(4)) to test their differentiation capacity. The transplantation was carried out by female donors to male recipients, and vice versa. One week after transplantation, GFP antigen-positive cells with phenotypic characteristics of hepatocytes were noted. After two weeks, their extent increased, and at 4 weeks, large areas of strongly GFP-stained cells developed. All recipient livers had GFP antigen-positive hepatocyte cells. PCR analysis coupled with laser capture micro-dissection (LCM) revealed those cells to contain GFP DNA. Thus, our results indicate that tissue stem cells have multipotential ability, differentiating into hepatocytes when transplanted into an injured liver.

Decrease in size of azoxymethane induced colon carcinoma in F344 rats by 180-day fermented miso.

The present study was designed to investigate the effects of fermented miso (fermented soybean paste) on the induction of colon tumors by azoxymethane (AOM) in male F344 rats. A total of 91 rats, 6 weeks of age, were divided into 5 groups and given weekly subcutaneous injections of AOM (15 mg/kg body wt) for 3 weeks. The animals were placed on diets one week before the first AOM dose: commercial normal control MF diet or a diet containing 10% 2-year, 180-day fermented, or 3-4-day fermented miso. There were no differences in body and organ weights, and no aberrant crypt foci (ACF) among carcinogen-treated groups at week 25. The rates of tumor incidence were 45%, 85%, 75% and 60% with the 2-year, 180-day, and 3-4-day fermented miso and MF, respectively, and those for colon tumors were 34%, 55%, 60% and 55%, respectively. The size of well-differentiated adenocarcinomas and total (well differentiated and signet ring cell) adenocarcinomas in the 180-day fermented miso group was significantly smaller than that in the 2-year fermented miso and MF+AOM groups. Nuclear staining of beta-catenin in colon tumors was increased for the 3-4-day fermented miso compared to the 180-day fermented miso. Cdx2 staining tendency was decreased in colon tumors and adenocarcinomas compared to normal mucosa and ACF, which stained in 100% of cases. In addition, the PCNA index was significantly reduced in the 180-day group compared with those groups receiving the 3-4-day fermented miso and MF diet. The germinal region was also decreased. The present results indicate that dietary supplementation with 180-day fermented dietary miso could act as a chemopreventive agent for colon carcinogenesis.