Location: Location not imported yet.Title: Impact of obesity on the toxicity of a multi-ingredient dietary supplement, OxyELITE Pro (New Formula), using the novel NZO/HILtJ obese mouse model: Physiological and mechanistic assessments
|SKINNER, CHARLES - University Arkansas For Medical Sciences (UAMS)
|MIOUSSE, ISABELLE - University Arkansas For Medical Sciences (UAMS)
|EWING, LAURA - University Arkansas For Medical Sciences (UAMS)
|SRIDHARAN, VIJAYALAKSHMI - University Arkansas For Medical Sciences (UAMS)
|CAO, MAOHUA - University Arkansas For Medical Sciences (UAMS)
|LIN, HAIXIA - University Arkansas For Medical Sciences (UAMS)
|WILLIAMS, KEITH - University Arkansas For Medical Sciences (UAMS)
|AVULA, BHARATHI - University Of Mississippi
|HAIDER, SAQLAIN - University Of Mississippi
|AMAR, CHITTIBOYINA - University Of Mississippi
|KHAN, IKHLAS - University Of Mississippi
|ELSOHLY, MAHMOUD - Elsohly Laboratories, Inc
|BOERMA, MARJAN - University Arkansas For Medical Sciences (UAMS)
|GURLEY, BILL - University Arkansas For Medical Sciences (UAMS)
|KOTURBASH, IGOR - University Arkansas For Medical Sciences (UAMS)
Submitted to: Food and Chemical Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/28/2018
Publication Date: 12/1/2018
Citation: Skinner, C.M., Miousse, I.R., Ewing, L.E., Sridharan, V., Cao, M., Lin, H., Williams, D.K., Avula, B., Haider, S., Amar, C.G., Khan, I.A., Elsohly, M.A., Boerma, M., Gurley, B.J., Koturbash, I. 2018. Impact of obesity on the toxicity of a multi-ingredient dietary supplement, OxyELITE Pro (New Formula), using the novel NZO/HILtJ obese mouse model: Physiological and mechanistic assessments. Food and Chemical Toxicology. 122:21-32. https://doi.org/10.1016/j.fct.2018.09.067.
Interpretive Summary: Dietary supplement OxyELITE Pro-New Formula (OEP-NF), is linked to severe liver injuries in the United States, which was marketed for weight loss and exercise performance enhancement. It contains multi-ingredient phytochemicals, e.g. synthetic caffeine, yohimbine, and aegeline. OEP-NF-associated liver injury was reported mostly in overweight or obese patients. It is plausible that obesity can exacerbate OEP-NF-induced cardiac and hepatic toxicity in humans. In this study, a novel NZO/HILtJ obese mouse model exhibiting impaired glucose tolerance was utilized to assess the short- and long-term toxicity of OEP-NF. Groups of female NZO/HILtJ mice were orally gavaged with OEP-NF (as a daily bolus) for two weeks which mimicked the ingestion of a single maximum recommended dose in humans or fed with diets containing OEP-NF for 8 weeks which was allometrically equivalent to consumption suggested by the product label. We demonstrated that OEP-NF produced significant hepatic- and cardiotoxicity in obese NZO/HILtJ mice at the levels equivalent to human daily recommended doses. The majority of gene expression was altered in the 8-week feeding study, which was consistent with our previous findings in CD-1 and B6C3F1 mice (non-obese strains) but was much higher in the magnitude of changes among NZO/HILtJ mice, suggestive of the impact of obesity on OEP-NF-induced toxicity. Of them, several altered genes are involved in hepatic de novo lipogenesis and adiposity, indicating overweight/obese consumers whose conditions are usually attended with fatty liver are exquisitely sensitive to the toxic effects of OEP-NF. Additionally, cardiac functional changes using ultrasonography, increased apoptotic and mast cells, and altered protein levels associated with inflammation indicate the prolonged intake of the alkaloid combination present in OEP-NF can cause adverse effects on cardiac structure and function in the obese mouse model. These findings suggest OEP-NF possesses significant hepatotoxicity and cardiotoxicity in NZO/HILtJ mice and overweight/obesity may exacerbate OEP-NF-induced toxicity.
Technical Abstract: Herbal dietary supplement (HDS)-induced hepato- and cardiotoxicity is an emerging clinical problem. In this study, we investigated the liver and heart toxicity of HDS OxyELITEPRO New Formula (OEP-NF), a dietary supplement marketed for weight loss and performance enhancement that was recently withdrawn from the market. Using a novel NZO/HlLtJ obese mouse model, we demonstrated that administration of clinically relevant mouse equivalent doses (MED) of OEP-NF produced cardio- and hepatotoxic risks following both short- and long-term administration schedules. Specifically, gavaging female NZO/HlLtJ with up to 2X MED of OEP-NF resulted in 40% mortality within two weeks. Feeding mice with either 1X or 3X MED of OEP-NF for eight weeks, while not exhibiting significant effects on body weights, significantly altered hepatic gene expression, increased the number of apoptotic and mast cells in the heart and affected cardiac function. The degree of toxicity in NZO/HlLtJ mice was higher than that observed previously in non-obese CD-1 and B6C3F1 strains, suggesting that an overweight/obese condition can sensitize mice to OEP-NF. Adverse health effects linked to OEP-NF, together with a number of other hepato- and cardiotoxicity cases associated with HDS ingestion, argue strongly for introduction of quality standards and pre-marketing safety assessments for multi-ingredient HDS.