Effects of Agaricus brasiliensis mushroom in Walker-256 tumor-bearing rats.

Agaricus brasiliensis is a mushroom native to São Paulo State, Brazil, that is studied for its medicinal proprieties. This work aimed to investigate the antitumoral activity of A. brasiliensis extracts and pure powdered basidiocarp preparation using Walker-256 (W256) tumor-bearing rats, a model for cancer-related cachexia studies. The rats were treated for 14 days by gavage (136 mg/kg) and at the end of the experiment tumors were collected to calculate mass and volume. Blood was collected for determination of plasma glucose, albumin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Hepatic and tumor enzymes indicating oxidative stress were also evaluated. The results showed that all 4 treatments (pure powdered basidiocarp and aqueous, acid, and alkaline extracts) significantly reduced tumor size and promoted gain in body weight. Plasmatic analysis showed a reduction in AST level and increased glycemia in the treated rats. Pure basidiocarp preparations improved the liver catalase and superoxide dismutase activity, but did not change the glutathione S-transferase activity. The data collected from the W256 tumor-bearing rats revealed the beneficial effects of A. brasiliensis in tumor treatment, mainly related to cachexia. The benefits can be partly related to antioxidant activity and to reduction of weight loss and tumor growth.

Effects of the venom and the dermonecrotic toxin LiRecDT1 of Loxosceles intermedia in the rat liver.

Brown spider bites cause dermonecrotic lesions and systemic manifestations known as loxoscelism. The Loxosceles intermedia venom contains many active proteins, as phospholipase D. There are reports of increased levels of hepatic transaminases in humans with loxoscelism, but detailed studies about the action of the Loxosceles intermedia venom on the liver functions are lacking. The aim of this study was to investigate the effects of the venom and the dermonecrotic recombinant toxin 1 (LiRecDT1) in the liver of Wistar rats injected subcutaneously with venom (80 microg) or toxin (80 microg). After 6 and 12h the liver immunofluorescence was positive for venom and toxin. Hepatocytes from the venom group were tumefacted and apoptotic. There was leucocyte infiltration in the portal region combined with a high degree of steatosis in 12h. In the toxin group the histological alterations were less severe. Plasma levels of alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl-transferase were significantly elevated only in the venom group in 6h. Hepatic metabolism was modified: the venom, but not LiRecDT1, reduced gluconeogenesis and ureagenesis from alanine and glycogen accumulation. These results show that the venom is hepatotoxic and that the dermonecrotic toxin is only partly responsible.

Celecoxib prevents tumor growth in an animal model by a COX-2 independent mechanism.

PURPOSE: Nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to reduce cell growth in several tumors. Among these possible antineoplastic drugs are cyclooxygenase- 2 (COX-2)-selective drugs, such as celecoxib, in which antitumoral mechanisms were evaluated in rats bearing Walker-256 (W256) tumor. METHODS: W256 carcinosarcoma cells were inoculated subcutaneously (10(7) cells/rat) in rats submitted to treatment with celecoxib (25 mg kg(-1)) or vehicle for 14 days. Tumor growth, body-weight gain, and survival data were evaluated. The mechanisms, such as COX-2 expression and activity, oxidative stress, by means of enzymes and lipoperoxidation levels, and apoptosis mediators were also investigated. RESULTS: A reduction in tumor growth and an increased weight gain were observed. Celecoxib provided a higher incidence of survival compared with the control group. Cellular effects are probably COX-2 independent, because neither enzyme expression nor its activity, measured by tumoral PGE(2), showed significant difference between groups. It is probable that this antitumor action is dependent on an apoptotic way, which has been evaluated by the expression of the antiapoptotic protein Bcl-xL, in addition to the cellular changes observed by electronic microscopy. Celecoxib has also a possible involvement with redox homeostasis, because its administration caused significant changes in the activity of oxidative enzymes, such as catalase and superoxide dismutase. CONCLUSION: These results confirm the antitumor effects of celecoxib in W256 cancer model, contributing to elucidating its antitumoral mechanism and corroborating scientific literature about its effect on other types of cancer.