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

Charles M Skinner; Isabelle R Miousse; Laura E Ewing; Vijayalakshmi Sridharan; Maohua Cao; Haixia Lin; D Keith Williams; Bharathi Avula; Saqlain Haider; Amar G Chittiboyina; Ikhlas A Khan; Mahmoud A ElSohly; Marjan Boerma; Bill J Gurley; Igor Koturbash

doi:10.1016/j.fct.2018.09.067

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 Chem Toxicol. 2018 Dec:122:21-32. doi: 10.1016/j.fct.2018.09.067. Epub 2018 Sep 30.

Authors

Affiliations

¹ Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA; Center for Dietary Supplement Research, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. Electronic address: CMSkinner@uams.edu.
² Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. Electronic address: IRacinemiousse@uams.edu.
³ Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA; Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. Electronic address: LEEwing@uams.edu.
⁴ Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, 72223, USA. Electronic address: VMohanseenivasan@uams.edu.
⁵ Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, 72223, USA. Electronic address: MCao@uams.edu.
⁶ Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. Electronic address: HLin@uams.edu.
⁷ Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. Electronic address: WilliamsDavidK@uams.edu.
⁸ National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS, 38677, USA. Electronic address: bavula@olemiss.edu.
⁹ National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS, 38677, USA. Electronic address: ssaqlain@olemiss.edu.
¹⁰ National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS, 38677, USA. Electronic address: amar@olemiss.edu.
¹¹ National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS, 38677, USA. Electronic address: ikhan@olemiss.edu.
¹² ElSohly Laboratories, Inc. (ELI), Phyto Chemical Services, Inc. (PSI), 5 Industrial Park Drive, Oxford, MS 38655, USA. Electronic address: melsohly@olemiss.edu.
¹³ Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, 72223, USA; Center for Dietary Supplement Research, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. Electronic address: mboerma@uams.edu.
¹⁴ Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, 72223, USA; Center for Dietary Supplement Research, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. Electronic address: GurleyBillyJ@uams.edu.
¹⁵ Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA; Center for Dietary Supplement Research, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. Electronic address: IKoturbash@uams.edu.

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 OxyELITE-PRO™ 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.

Keywords: Cardiotoxicity; Hepatotoxicity; Herbal-induced liver injury; New dietary ingredient; OXYElite pro; Phytochemicals.

MeSH terms

Administration, Oral
Animals
Cardiotoxicity / etiology*
Chemical and Drug Induced Liver Injury / etiology*
Chromatography, High Pressure Liquid / methods
Dietary Supplements / analysis
Dietary Supplements / toxicity*
Disease Models, Animal*
Echocardiography
Feeding Behavior
Female
Gene Expression Profiling
Liver / drug effects
Liver / metabolism
Mice
Myocardium / metabolism
Obesity / genetics
Obesity / metabolism
Obesity / physiopathology*
Phytochemicals / toxicity*

Substances

Phytochemicals

Grants and funding

P20 GM109005/GM/NIGMS NIH HHS/United States