Publications

The use of herbs has been advocated as an alternative treatment strategy for human immunodeficiency virus-related illness. To describe the use of medicinal herbs among acquired immunodeficiency syndrome clinic patients and to investigate possible toxic effects, we interviewed 114 randomly selected patients attending a university-based acquired immunodeficiency syndrome clinic and performed a structured review of the literature to identify potential adverse effects of herbal use. Twenty-five participants (22%) reported using one or more herbal products in the past 3 months. Of those taking herbs, six (24%) were unable to identify the herb that they had used. The mean number of herbal tablets taken was 4.5 tablets per day, and 12 patients (48%) reported taking herbs for longer than 90 days. The median cost to patients for their herbs was $18 per month. Of those taking herbs, five (20%) stated that their primary medical provider was unaware of their herb use, and four (16%) were involved in clinical drug trials while using herbs. Several patients reported taking herbs in doses at which potential adverse effects were identified in our literature review. These adverse effects include dermatitis, nausea, vomiting, diarrhea, thrombocytopenia, coagulopathies, altered mental status, hepatotoxicity, and electrolyte disturbances. Seven patients (28%) reported experiencing symptoms that could have been caused by one or more of the herbal products that they were taking. Physicians and clinical investigators need to inquire about patients' use of herbs. Patient care and clinical trials could be distorted because pharmacologic effects of herbs can resemble commonly occurring symptoms in human immunodeficiency virus disorders as well as side effects of prescribed or investigational medications.

We have previously reported that the diuretic thiosteroid spironolactone (SPL) inactivates rat liver microsomal cytochromes P450 [P450 (P450 3A and P450 2C11)] in a in a mechanism-based fashion, and we have identified two polar SPL metabolites (SPL-sulfinic acid and -sulfonic acid), formed in a partition ratio of approximately 20:1 in such rat liver microsomal incubations [Decker et al. (1989) Biochemistry 28, 5128-5136]. We proposed at the time that these metabolites were most likely derived from further enzymatic (or nonenzymatic) oxidations of the one-electron oxidation product [SPL-thiyl radical (SPL-S.)] and/or the two-electron-oxidized species [SPL-sulfenic acid (SPL-SOH)]. In those studies, glutathione (GSH) was found to attenuate both SPL-mediated P450 loss as well as polar metabolite formation by approximately 40%. We have now reexamined this in greater detail and report that it is due to GSH trapping of an electrophilic oxidized SPL species to form an adduct that we have isolated and unambiguously characterized by mass spectral analyses as the glutathionyl-SPL adduct (SPL-SSG). Moreover, we have found not only that rat liver microsomal formation of this adduct is enhanced at pH 9.0, the pH optimum for flavin-containing monooxygenase (FMO), but also that such adduct formation was indeed efficiently catalyzed by purified hog liver FMO. Because FMO oxidations of thiols are thought to entail a two-electron process to form the corresponding sulfenic acids, we infer that such a SPL-SSG adduct most likely reflects FMO-catalyzed oxidation of SPL to SPL-SOH, which on leaving the FMO active site is then trapped by GSH.(ABSTRACT TRUNCATED AT 250 WORDS)