Entry #: 52
Date: 31 May 2018
Section: Phenolic extracts
Topic: Phenolic extracts and bisphenol A toxicity
Type: In vivo model

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Expert review of literature related to olives and olive oil

D. Elizabeth McCord, Nancy B. Ray and Tom C. Karagiannis


Oleuropein and hydroxytyrosol rich extracts from olive leaves attenuate liver injury and lipid metabolism disturbance in bisphenol A-treated rats


Mahmoudi et al

Citation / Year

(1) / 2018


Oleuropein, hydroxytyrosol, phenolic compounds, liver injury, metabolism, triglycerides, cholesterol, inflammation


Exposure to endocrine-disrupting chemicals, such as bisphenol A, which are found in food packaging and insecticides, is very widespread (2). Epidemiological evidence has highlighted that these chemicals are associated with metabolic disorders including obesity and diabetes (3-5). The most widely produced and well-investigated endocrine disrupting compound is bisphenol A, which is widely used in epoxy resins and plastic packaging (6). Chemically, it is analogous to estrogen and has been shown to be associated with a wide variety of diseases including cancer, cardiovascular disease, and type 2 diabetes (7). Oxidative stress, induction of apoptosis, and hepatotoxicity are underlying mechanisms by which bisphenol A causes pathological conditions (8-10). The anti-inflammatory and antioxidant effects of key olive phenolics such as oleuropein and hydroxytyrosol are well known. Of particular interest with respect to this study is the finding that olive leaf extracts can prevent fluoxetine-induced liver damage by mechanisms involving reductions in oxidative stress, inflammation, and apoptosis (11). In this study the effects of olive leaf extracts on bisphenol A-induced toxicity in rats was investigated.

Key points and implications

For this study extracts enriched for oleuropein or hydroxytyrosol were prepared, and the composition was confirmed by HPLC analysis. Rats (5-week old, four groups of eight animals per group), were divided into: 1) control group, 2) bisphenol A group (10 mg per kg per day in drinking water), 3) bisphenol A-oleuropein group (16 mg per kg oleuropein by gavage), and 4) bisphenol A-hydroxytyrosol group (16 mg per kg hydroxytyrosol by gavage); the experiment was conducted over a period of 60 days. During and following the experiment, classical histopathological, biochemical and protein-based parameters were monitored to evaluate the effects of the olive phenolics on bisphenol A-induced toxicity. In summary, the key findings indicate that bisphenol-A has severe effects body weight, adipose tissue mass, and increased plasma levels of cholesterol and triglycerides, liver function enzymes, and pro-inflammatory markers. The oleuropein and hydroxytyrosol enriched phenolic extracts both had remarkable effects, including: 1) reducing body weight and adipose tissue mass, 2) decreasing plasma levels of liver enzymes (a mechanism which the authors ascribe possibly to enhanced catalase and superoxide dismutase activities), and 3) dampening inflammatory pathways (NF-κB, TNF-α). Overall, these findings highlight the potential beneficial effects of olive phenolic extracts in preventing hepatotoxicity and metabolic effects from noxious environmental compounds, in this case bisphenol A.

Related publications

  1. A. Mahmoudi et al., Oleuropein and hydroxytyrosol rich extracts from olive leaves attenuate liver injury and lipid metabolism disturbance in bisphenol A-treated rats. Food & function, (2018).
  2. A. M. Calafat, X. Ye, L. Y. Wong, J. A. Reidy, L. L. Needham, Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003-2004. Environmental health perspectives 116, 39-44 (2008).
  3. J. Ukropec et al., High prevalence of prediabetes and diabetes in a population exposed to high levels of an organochlorine cocktail. Diabetologia 53, 899-906 (2010).
  4. D. Melzer, N. E. Rice, C. Lewis, W. E. Henley, T. S. Galloway, Association of urinary bisphenol a concentration with heart disease: evidence from NHANES 2003/06. PloS one 5, e8673 (2010).
  5. H. Uemura et al., Associations of environmental exposure to dioxins with prevalent diabetes among general inhabitants in Japan. Environmental research 108, 63-68 (2008).
  6. J. J. Pritchett, R. K. Kuester, I. G. Sipes, Metabolism of bisphenol a in primary cultured hepatocytes from mice, rats, and humans. Drug metabolism and disposition: the biological fate of chemicals 30, 1180-1185 (2002).
  7. J. Mendiola et al., Are environmental levels of bisphenol a associated with reproductive function in fertile men? Environmental health perspectives 118, 1286-1291 (2010).
  8. Y. B. Wetherill et al., In vitro molecular mechanisms of bisphenol A action. Reproductive toxicology 24, 178-198 (2007).
  9. V. Bindhumol, K. C. Chitra, P. P. Mathur, Bisphenol A induces reactive oxygen species generation in the liver of male rats. Toxicology 188, 117-124 (2003).
  10. M. K. Moon et al., Bisphenol A impairs mitochondrial function in the liver at doses below the no observed adverse effect level. Journal of Korean medical science 27, 644-652 (2012).
  11. H. A. Elgebaly et al., Olive oil and leaf extract prevent fluoxetine-induced hepatotoxicity by attenuating oxidative stress, inflammation and apoptosis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 98, 446-453 (2018).