RESUMO
A recent surge in the use of dietary supplements, including herbal remedies, necessitates investigations into their safety profiles. "Dream herb," Calea zacatechichi, has long been used in traditional folk medicine for a variety of purposes and is currently being marketed in the US for medicinal purposes, including diabetes treatment. Despite the inherent vulnerability of the renal system to xenobiotic toxicity, there is a lack of safety studies on the nephrotoxic potential of this herb. Additionally, the high frequency of diabetes-associated kidney disease makes safety screening of C. zacatechichi for safety especially important. We exposed human proximal tubule HK-2 cells to increasing doses of this herb alongside known toxicant and protectant control compounds to examine potential toxicity effects of C. zacatechichi relative to control compounds. We evaluated both cellular and mitochondrial functional changes related to toxicity of this dietary supplement and found that even at low doses evidence of cellular toxicity was significant. Moreover, these findings correlated with significantly elevated levels of nephrotoxicity biomarkers, lending further support for the need to further scrutinize the safety of this herbal dietary supplement.
RESUMO
Adhatoda zeylanica is a dietary supplement ingredient present in several types of dietary supplements, including weight loss, respiratory relief, and immune regulating products. Due to its reported wide range of uses in folk medicine, it was hypothesized that it may have the potential to target multiple organs and lead to a range of toxicity features. As a preliminary evaluation of the safety of this herbal ingredient, an investigation into its effects on the kidney was sought. An in vitro study of its potential nephrotoxicity using the HK-2 human proximal tubule cell line in a variety of functional indicators was performed to capture both general forms of cellular toxicity as well as ones that are specific to proximal tubules. A. zeylanica was only capable of inducing detrimental short-term toxicity to HK-2 cells at relatively high treatment concentrations when exposed directly to the cells. The lack of acute and potent toxicity of A. zeylanica under our experimental conditions calls for further studies to better define its toxicant threshold and establish safe dosage levels.
RESUMO
Some dietary supplements may contain cardiac stimulants and potential cardiotoxins. In vitro studies may identify ingredients of concern. A beating human cardiomyocyte cell line was used to evaluate cellular effects following phenylethylamine (PEA), higenamine, ephedrine or caffeine treatment. PEA and higenamine exposure levels simulated published blood levels in humans or animals after intravenous administration. Ephedrine and caffeine levels approximated published blood levels following human oral intake. At low or midrange levels, each chemical was examined plus or minus 50 µM caffeine, simulating human blood levels reported after consumption of caffeine-enriched dietary supplements. To measure beats per minute (BPM), peak width, etc., rhythmic rise and fall in intracellular calcium levels following 30 min of treatment was examined. Higenamine 31.3 ng/ml or 313 ng/ml significantly increased BPM in an escalating manner. PEA increased BPM at 0.8 and 8 µg/ml, while 80 µg/ml PEA reduced BPM and widened peaks. Ephedrine produced a significant BPM dose response from 0.5 to 5.0 µM. Caffeine increased BPM only at a toxic level of 250 µM. Adding caffeine to PEA or higenamine but not ephedrine further increased BPM. These in vitro results suggest that additional testing may be warranted in vivo to further evaluate these effects.
Assuntos
Alcaloides/toxicidade , Cafeína/toxicidade , Suplementos Nutricionais/toxicidade , Efedrina/toxicidade , Miócitos Cardíacos/efeitos dos fármacos , Fenetilaminas/toxicidade , Tetra-Hidroisoquinolinas/toxicidade , Animais , Cardiotônicos/toxicidade , Cardiotoxicidade/patologia , Células Cultivadas , Coração/efeitos dos fármacos , Humanos , Ratos , Testes de ToxicidadeRESUMO
Rauwolfia serpentina (or Snake root plant) is a botanical dietary supplement marketed in the USA for maintaining blood pressure. Very few studies have addressed the safety of this herb, despite its wide availability to consumers. Its reported pleiotropic effects underscore the necessity for evaluating its safety. We used a human kidney cell line to investigate the possible negative effects of R. serpentina on the renal system in vitro, with a specific focus on the renal proximal tubules. We evaluated cellular and mitochondrial toxicity, along with a variety of other kidney-specific toxicology biomarkers. We found that R. serpentina was capable of producing highly detrimental effects in our in vitro renal cell system. These results suggest more studies are needed to investigate the safety of this dietary supplement in both kidney and other target organ systems.
Assuntos
Células Epiteliais/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rauwolfia/química , Espécies Reativas de Oxigênio/agonistas , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Cistatina C/genética , Cistatina C/metabolismo , Relação Dose-Resposta a Droga , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Receptor Celular 1 do Vírus da Hepatite A , Humanos , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Receptores Virais/genética , Receptores Virais/metabolismo , Ácido Valproico/farmacologia , Microglobulina beta-2/genética , Microglobulina beta-2/metabolismoRESUMO
Androstenedione, a naturally occurring steroid hormone, is a dietary supplement used to enhance athletic performance. Little is known, however, about the safety of its use by young adults including women of child bearing age. To test the possible hepatotoxic effects of androstenedione use, this study was undertaken using a rat model. Pregnant rats (six rats/dose) were exposed to androstenedione in corn oil by gastric intubation at 0, 5, 30 or 60 mg/kg body weight/day beginning 2 weeks before mating and continuing through gestation day 19. On gestation day 20, blood and livers were collected from the pregnant rats for analysis of hepatotoxicity endpoints: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), glutathione (GSH) and glutathione S-transferase (GST), total microsomal P450, nuclear DNA damage and lipid peroxidation. Under these experimental conditions, no significant differences were observed in any of these biomarkers over the concentration range examined.