Extra Virgin olive oil mitigates hematotoxicity induced by acrylamide and oxidative damage in adult rats

Introduction Acrylamide (ACR) is used in various scientific and industrial processes, such as water treatment, in cosmetics and gel electrophoresis (1). The primary route of ACR exposure for people is through drinking water and food consumption. It is formed in carbohydrate rich foods cooked at high temperatures through interactions of amino acids with reduced sugar (Maillard reaction) (2). ACR forms conjugates with reduced glutathione (GSH). Then the resulting complex is metabolized by cytochrome P450 (CYP 2E1) pathway to form glycidamide (3). The last metabolite is genotoxic leading to the formation of hemoglobin and glycidamide-DNA adducts (4). It accumulates at higher levels in the blood than any other tissues following exposure via oral ingestion, inhalation, or via the dermis (5). Moreover, ACR caused a disruption of hematological parameters, a decrease in erythrocyte membrane resistance and retarded synthesis or destruction of Hb (6-8). Then, an imbalance between the production of reactive oxygen species (ROS) and antioxidant capacity increased oxidative stress playing a critical role in the toxicity induced by ACR through the lipid peroxidation increase and the impairment of endogenous antioxidant biomarkers (9-11). ROS are produced in erythrocytes by a process known as redox cycling and are catalyzed by transition metals, such as Fe and Cu(12). Natural dietary antioxidants have been used to protect cells against oxidative damage through scavenging free radicals. Extra Virgin Olive oil (EVOO), one of the most important food products consumed in Mediterranean countries, has been shown to be effective against oxidative stress. EVOO has many applications including cooking, cosmetics, pharmaceutical preparations and soaps. Olive oil, unlike other vegetable oils, contains high amounts of several micronutrient constituents, including polyphenolic compounds such as hydroxytyrosol, tyrosol, and oleuropein (13). It has also been shown to have anti-inflammatory, antithrombotic, antihypertensive and vasodilatory effects in both animals and humans (14). The possible mechanism explaining the beneficial role of EVOO may be due to its contents of monounsaturated fatty acids (MUFA) essentially oleic acid and polyphenols as reported by our previous studies (15,16). Data assessing the health effects of EVOO used as a dietary supplement after acrylamide treatment are lacking. The underlying mechanisms responsible for any Abstract Acrylamide (ACR) is a dietary contaminant derived from a wide range of foods through the Maillard-reaction during the cooking process. The present study focused on the hematotoxic effects of ACR and the protective efficacy of Extra Virgin olive oil (EVOO) in alleviating hematotoxicity and oxidative stress in erythrocytes of adult rats. Rats were divided into four groups of six each: group 1, serving as negative controls, received distilled water; group 2 received by gavage ACR at a dose of 40 mg/ kg body weight; group 3 received by gavage ACR supplemented with EVOO (300 μL); group 4,serving as positive controls, received only EVOO by gavage. All groups were sacrificed after three weeks. Acrylamide induced a significant increase in white blood cells (WBC), erythrocyte osmotic fragility (OF) and a decrease in red blood cells (RBC), hemoglobin (Hb) and hematocrit (Ht). While mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and MCH concentration (MCHC) remained unchanged. Furthermore, exposure of rats to ACR induced erythrocytes oxidative stress with an increase of malondialdehyde, hydrogen peroxide, and protein carbonyls levels. A reduction in antioxidant status, enzymatic (catalase, glutathione peroxidase and superoxide dismutase) and non enzymatic (reduced glutathione, non protein thiols and vitamin C) was observed when compared to controls. EVOO supplementation alleviated significantly hematotoxicity induced by acrylamide as evidenced by restoring the biochemical markers cited above to near normal values. Our results revealed that extra virgin olive oil, a main component of olive Mediterranean diet, was effective in preventing erythrocytes damage and oxidative stress.