Vitamin D2 from UVB light exposed mushrooms modulates immune response to LPS in rats.

SCOPE: Poor vitamin D (vitD) status is linked to increased risk of infectious diseases, thus there is need for vitD-rich foods. UVB-exposed mushrooms synthesize vitD2 but knowledge of bioavailability and function in immune response is lacking. METHODS AND RESULTS: One hundred rats were fed one of five diets--control, 20 IU vitD3/day; no vitD3/day; 5% unexposed mushroom, 2.4 IU vitD2/day; 2.5% UVB mushroom, 300 IU vitD2/day; and 5% UVB mushroom, 600 IU vitD2/day--for 10 wk and challenged with either saline or the endotoxin LPS. Blood and tissues were collected at 3 h postchallenge. Plasma 25-hydroxyvitamin D (25OHD) levels from UVB-exposed mushroom fed rats were significantly elevated and associated with higher natural killer cell activity and reduced plasma inflammatory response to LPS compared to control diet fed rats. Microarray evaluation of rat spleens for changes in inflammatory gene expression showed significant upregulation of proinflammatory genes after LPS compared to saline controls in all groups. However, compared to control rats, upregulation of the proinflammatory genes was markedly reduced in the groups fed vitD2-enriched mushrooms. CONCLUSION: Rats fed UVB-exposed mushrooms had significantly higher plasma total 25OHD levels that were associated with increased innate immune response and anti-inflammatory effects.

Rat liver clone-9 cells in culture as a model for screening hepatotoxic potential of food-related products: hepatotoxicity of deoxynivalenol.

Deoxynivalenol (DON) is a mycotoxin food contaminant found in several cereal grains. The literature on the liver toxicity of DON in vivo is conflicting and does not clearly characterize its hepatotoxic effects. Cultured rat liver clone-9 cells were used as a model to assess the hepatotoxic potential of DON. The cell cultures, seeded onto 96-well plates, were treated at confluence with varying concentrations of DON (0-100 microg ml(-1)) for 48 h at 37 degrees C in 5% CO2. After the treatment period, the cells were assayed for a number of hepatotoxic endpoints that included cytotoxicity, double-stranded DNA (ds-DNA) content, oxidative stress and mitochondrial function. The concentration-dependent toxicity of DON, as measured by cytotoxicity and ds-DNA content, was observed over the entire concentration range studied beginning at 0.5 microg ml(-1). DON also induced a significant concentration-dependent increase in oxidative stress at DON concentrations starting at 10 microg ml(-1). The mitochondrial function of the treated cells decreased with the increasing concentration of DON exposure, but it was not statistically different from that of the control value. Liver histopathology observed at 3, 24 and 72 h following a single intraperitoneal administration dose of DON (10 mg kg(-1) BW) to adult male rats is consistent with early mild hepatotoxicity. The overall results of this study suggest that acute DON exposure has early mild cytotoxic effects on hepatocytes in vivo that are expressed as severe effects in rat liver clone-9 cells in vitro.

Acute oral toxicity of colchicine in rats: effects of gender, vehicle matrix and pre-exposure to lipopolysaccharide.

The oral toxicity of a single administration by gavage (10, 20 or 30 mg kg(-1) body weight) of colchicine (COL) was determined in young, mature male and female Sprague-Dawley rats. The effect of COL was evaluated in the presence or absence of additional treatment variables that included vehicle and lipopolysaccharide (LPS) pre-exposure. The vehicle for COL was either Half and Half cream (H & H) or saline, and each group included pretreatment with either saline or a low, minimally toxic dose (83 microg kg(-1) body weight) of LPS. Colchicine toxicity in both male and female age-matched rats was characterized by progressively more severe dose-related clinical signs of toxicity. These included mortality, decreased body weight and feed intake during the first several days after dosing, with recovery thereafter in surviving animals. There were differences in the severity of the toxic response to COL between male and female rats. The most notable sex-related difference was in COL lethality. Female rats were two times more susceptible to the lethal effects of COL than male rats. Saline or H & H delivery vehicles did not result in any apparent qualitative or quantitative differences in COL toxicity. LPS pretreatment significantly potentiated COL lethality in both males and females, although the potentiation in males was greater than in females. LPS pretreatment modestly increased the COL induced anorexic effect in surviving males, but not in surviving female animals. LPS did not appear to modulate either the body weights or clinical signs of COL induced toxicity in surviving males or females.