Oleuropein-Rich Olive Leaf Extract Protects Mouse Liver in Cadmium-Induced Toxicity

by | Apr 26, 2021 | 2020, Antioxidants, Heavy Metals, Liver Health

Written by Angeline A. De Leon, Staff Writer. An oleuropein-rich extract, with its antiapoptotic, anti-inflammatory, and antioxidant properties, significantly reduced cadmium-induced toxicity in the liver cells of mice.

liver healthCadmium (Cd) is a naturally occurring metal associated with various kinds of cancer and toxic effects in the organ system, particularly the kidneys, heart, and liver 1,2. Exposure to Cd, through air, water, food, or soil, is linked to a number of adverse biological effects, including increased oxidative stress and apoptosis 3,4 and changes in DNA and gene expression 5, making it one of the most harmful environmental pollutants. Given Cd’s direct involvement in oxidative stress pathways 2, Cd detoxification therapies have focused on using mineral antioxidants like polyphenols to prevent Cd toxicity 6. Previous research, for example, has identified zinc as a phytochemical with significant protective effects against Cd exposure 4. Another promising antioxidant compound in terms of heavy metal detoxification potential is oleuropein, a phenolic compound found in olive leaves and linked to powerful antioxidant, anti-inflammatory activity  7. Both in vivo and in vitro studies have confirmed the protective effects of olive leaf oleuropein against Cd toxicity in the kidneys 8,9, however, its impact on liver tissue is yet unknown. Thus, a recent 2020 study 10 in BioMed Research International sought to investigate the hepatoprotective effects of oleuropein against Cd toxicity in mice.

A litter of 18 male mice were divided into three groups, one group receiving an intraperitoneal injection of Cd (five doses of 0.4 Cd/kg by body weight over a 2-week period), the second receiving the same dose of Cd, along with 16 mg/kg by body weight of oleuropein-rich extract, and the third serving as a control group. Animals were sacrificed, and liver tissue samples harvested in order to estimate biomarkers of liver function, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH). Antioxidant activity was measured based on catalase (CAT) and superoxide dismutase (SOD) activity, and total antioxidant capacity (TAC) was evaluated in cytosolic liver samples. Lipid peroxidation in liver cytosol was measured according to thiobarbituric acid-reactive substances (TBARS) content in liver tissue (based on malondialdehyde [MDA] concentrations).

Experimental results indicated that treatment with oleuropein significantly attenuated Cd-induced increases in ALT, AST, ALP, and LDH (p < 0.01 for all parameters). Administration of Cd was also associated with a significant decrease in SOD and CAT activities, relative to controls (p < 0.001 for both), but this was significantly restored following treatment with oleuropein-rich extract (p < 0.01 for CAT, p < 0.001 SOD). Similarly, mice receiving Cd treatment demonstrated a significant reduction in TAC values, compared to controls (p < 0.001), however, administration of oleuropein produced a significant increase in hepatic TAC (p < 0.001). Finally, while Cd-exposed mice demonstrated significant elevations in MDA content, compared to controls (p < 0.001), lipid peroxidation of hepatic tissue was significantly inhibited in mice co-treated with oleuropein extract (p < 0.001).

Evidence from the present investigation confirms the toxic effects of Cd as an industrial heavy metal and suggests a therapeutic role of oleuropein in protecting against Cd-induced oxidative damage. Two weeks of treatment with oleuropein was seen to mitigate the liver damage caused by Cd exposure and restore antioxidant enzyme activity, based on SOD, CAT, and TAC levels. By lowering TBARS concentrations (MDA content), oleuropein-rich extract also effectively reversed peroxidative damage in the liver resulting from Cd exposure. Thus, findings suggest that the prophylactic effects of oleuropein as a mineral antioxidant with heavy metal detoxification potential relate not only to the kidneys and heart, but to the liver as well. The hepatoprotective effects of oleuropein warrant confirmation in human subjects and further testing to establish optimal dose-response relations.

Source: Jemai H, Mahmoudi A, Feryeni A, et al. Hepatoprotective effect of oleuropein-rich extract from olive leaves against cadmium-induced toxicity in mice. BioMed Research International. 2020: 4398924. DOI: 10.1155/2020/4398924.

© 2020 Hedya Jemai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Click here to read the full text study.

Posted April 26, 2021.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

References:

  1. Buha A, Matovic V, Antonijevic B, et al. Overview of Cadmium Thyroid Disrupting Effects and Mechanisms. Int J Mol Sci. 2018;19(5).
  2. Xia L, Chen S, Dahms HU, Ying X, Peng X. Cadmium induced oxidative damage and apoptosis in the hepatopancreas of Meretrix meretrix. Ecotoxicology (London, England). 2016;25(5):959-969.
  3. Gebhardt R. Prevention of cadmium-induced toxicity in liver-derived cells by the combination preparation Hepeel(®). Environ Toxicol Pharmacol. 2009;27(3):402-409.
  4. Jemai H, Lachkar HA, Messaoudi I, Kerkeni A. Effects of zinc pre-treatment on blood glutathione, serum zinc and kidney histological organisation in male rats exposed to cadmium. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2010;24(4):277-282.
  5. Nemmiche S, Chabane-Sari D, Kadri M, Guiraud P. Cadmium-induced apoptosis in the BJAB human B cell line: involvement of PKC/ERK1/2/JNK signaling pathways in HO-1 expression. Toxicology. 2012;300(3):103-111.
  6. Bulat Z, Đukić-Ćosić D, Antonijević B, et al. Can zinc supplementation ameliorate cadmium-induced alterations in the bioelement content in rabbits? Arhiv za higijenu rada i toksikologiju. 2017;68(1):38-45.
  7. Maalej A, Mahmoudi A, Bouallagui Z, Fki I, Marrekchi R, Sayadi S. Olive phenolic compounds attenuate deltamethrin-induced liver and kidney toxicity through regulating oxidative stress, inflammation and apoptosis. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2017;106(Pt A):455-465.
  8. Jemai H, Feryéni A, Mahmoudi A, Fki I, Bouallagui Z, Sayadi S. Oleuropein protects kidney against oxidative and histopathological damages in subchronic cadmium intoxicated mice. 2019.
  9. Ranieri M, Di Mise A, Difonzo G, et al. Green olive leaf extract (OLE) provides cytoprotection in renal cells exposed to low doses of cadmium. PLoS One. 2019;14(3):e0214159.
  10. Jemai H, Mahmoudi A, Feryeni A, et al. Hepatoprotective Effect of Oleuropein-Rich Extract from Olive Leaves against Cadmium-Induced Toxicity in Mice. Biomed Res Int. 2020;2020:4398924.