Feeding of potato, tomato and eggplant alkaloids affects food consumption and body and liver weights in mice.
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Reduced liver weight was used to evaluate the potential toxicity in mice of four naturally occurring steroidal glycoalkaloids: alpha-chaconine and alpha-solanine, alpha-tomatine and solasonine. Increased liver weights was used to evaluate the three corresponding steroidal aglycones: solanidine, tomatidine, and solasodine and the non-alkaloid adrenal steroid dehydroepiandrosterone (DHEA). Adult female Swiss-Webster mice were fed diets containing test compound concentrations of 0 (control), 1.2, 2.4 or 4.8 mmol/kg diet for 7, 14 or 28 d. Absolute liver weights (LW) and relative liver weights (liver weight/body weight x 100, %LW/BW) were determined at autopsy. The %LW/BW was lower than that of controls in mice fed the potato glycoalkaloid alpha-chaconine (-10%, P < or = 0.05) for 7 d with the 2.4 mmol/kg diet dose. Under these same conditions, %LW/BW was greater than that of controls in mice fed two aglycones: solanidine (27%, P < or = 0.001) and solasodine (8%, P < or = 0.01). Relative liver weight increases induced by the aglycones were determined under time and dose conditions in which differences in body weight and food consumption were not significant (2.4 mmol/kg diet for 28 d). Under these conditions, the observed %LW/BW increases relative to the controls were as follows: solanidine (32%, P < or = 0.001), solasodine (22%, P < or = 0.001) and DHEA (16%, P < or = 0.001). Solanidine, solasodine and DHEA were equally potent and were more potent than tomatidine. We also observed that the greater %LW/BW in mice fed 2.4 mmol/kg diet solasodine or solanidine for 14 d declined to near control values if they were fed control diets for another 14 d. The increase in relative liver weight induced by solanidine and solasodine is a reversible adaptive response. These findings and the apparent effects of structure on biological activity should serve as a guide for the removal of the most toxic ++compounds from plant foods. The implications of the results for food safety and health are discussed. (+info)
Modulation of intrahepatic cholesterol trafficking: evidence by in vivo antisense treatment for the involvement of sterol carrier protein-2 in newly synthesized cholesterol transport into rat bile.
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Biliary cholesterol represents one of the two major excretory pathways for sterol elimination from the body and plays a central role in cholesterol gallstone formation. Biliary cholesterol originates from a precursor pool of preformed and newly synthesized free cholesterol. Although it has been suggested that newly synthesized and preformed biliary cholesterol are secreted by independent pathways, the specific cellular and molecular mechanisms are unknown. We used male Wistar rats to study the time-course of the appearance of newly synthesized cholesterol, phosphatidylcholine and protein into bile. The specific role of sterol carrier protein-2 (SCP-2) in the transport of newly synthesized biliary cholesterol was evaluated by an in vivo antisense oligonucleotide approach. In contrast to [14C]phosphatidylcholine and [35S]proteins, the time-course of [14C]cholesterol appearance into bile was rapid, and microtubule- and Golgi-independent. In vivo SCP-2 antisense treatment reduced and delayed the appearance of biliary [14C]cholesterol. Furthermore, hepatic SCP-2 expression increased more than 3-fold over control values in rats that had been treated with diosgenin to increase biliary secretion of newly synthesized cholesterol. These results suggest that SCP-2 is necessary for the rapid transport of newly synthesized cholesterol into bile and that hepatocytes can induce SCP-2 expression according to the rate of biliary secretion of newly synthesized cholesterol. (+info)