Isolation, purification, and full NMR assignments of cyclopamine from Veratrum californicum.

Background: The Hedgehog signaling pathway is essential for embryogenesis and for tissue homeostasis in the adult. However, it may induce malignancies in a number of tissues when constitutively activated, and it may also have a role in other forms of normal and maladaptive growth. Cyclopamine, a naturally occurring steroidal alkaloid, specifically inhibits the Hedgehog pathway by binding directly to Smoothened, an important Hedgehog response element.

Lack of formic acid production in rat hepatocytes and human renal proximal tubule cells exposed to chloral hydrate or trichloroacetic acid.

The industrial solvent trichloroethylene (TCE) and its major metabolites have been shown to cause formic aciduria in male rats. We have examined whether chloral hydrate (CH) and trichloroacetic acid (TCA), known metabolites of TCE, produce an increase in formic acid in vitro in cultures of rat hepatocytes or human renal proximal tubule cells (HRPTC). The metabolism and cytotoxicity of CH was also examined to establish that the cells were metabolically active and not compromised by toxicity.

Synthesis and pharmacology of ethylphenidate enantiomers: the human transesterification metabolite of methylphenidate and ethanol.

Ethanol elevates methylphenidate (1) plasma concentrations and yields the metabolite ethylphenidate (2). The therapeutic implications are under investigation. The IC(50) for dopamine reuptake inhibition by (+)-2 was 27 nM compared to 367 nM for cocaine and 1730 nM for (-)-2.

Role of oxidant stress in lawsone-induced hemolytic anemia.

Lawsone (2-hydroxy-1,4-naphthoquinone) is the active ingredient of henna (Lawsonia alba), the crushed leaves of which are used as a cosmetic dye. Application of henna can induce a severe hemolytic anemia, and lawsone is thought to be the causative agent. Administration of lawsone to rats has been shown to induce a hemolytic response that is associated with oxidative damage to erythrocytes.

High absorption but very low bioavailability of oral resveratrol in humans.

The dietary polyphenol resveratrol has been shown to have chemopreventive activity against cardiovascular disease and a variety of cancers in model systems, but it is not clear whether the drug reaches the proposed sites of action in vivo after oral ingestion, especially in humans. In this study, we examined the absorption, bioavailability, and metabolism of 14C-resveratrol after oral and i.v.

Primaquine-induced hemolytic anemia: susceptibility of normal versus glutathione-depleted rat erythrocytes to 5-hydroxyprimaquine.

Primaquine is an important antimalarial agent because of its activity against exoerythrocytic forms of Plasmodium spp. Methemoglobinemia and hemolytic anemia, however, are dose-limiting side effects of primaquine therapy. These hemotoxic effects are believed to be mediated by metabolites, although the identity of the toxic specie(s) and the mechanism underlying hemotoxicity have remained unclear.