Citrus aurantium L. peel extract mitigates hexavalent chromium-induced oxidative stress and cardiotoxicity in adult rats

Introduction Cardiovascular diseases (CVDs) remain one of the most important causes of mortality in the world. Commonly known risk factors, such as hypertension and hypercholesterolemia, can be responsible for only about 5075% of all CVDs. Therefore, there is an urgent need to identify new CVD risk factors. A great body of evidence indicates that heavy metal exposure is linked to increased incidence of heart diseases (1). Hexavalent chromium (Cr(VI)) is one of the valence states (+6) of the element chromium. It is usually produced by industrial processes and is a source of exposure in the workplace (2). The industrial applications of this metal include painting, electroplating, leather tanning and welding. Workers in Cr(VI)-based industries are highly exposed to this metal which is a major cause of concern. Excessive exposure to Cr(VI) can be associated with hepatotoxicity (3), nephrotoxicity (4) and carcinogenicity (5) in humans and experimental animals. Moreover, Cr(VI) has drawn considerable attention as one of the potential cardiotoxic heavy metals. In fact, this element has been demonstrated to accumulate in the heart tissue and to affect the cardiac function both in vivo and in vitro (6). In addition to that, Soudani et al. (7) have shown that Cr(VI) induces cardiotoxicity in adult rats. The excessive generation of reactive oxygen species (ROS) and the subsequent installation of oxidative stress have been reported to be responsible for the toxic effects of Cr(VI) in the heart (7). Herbal remedies have been used for the treatment of various illnesses including heart diseases (8). In fact, these herbs constitute a rich source of bioactive phytochemicals such as polyphenols, flavonoids, and other constituents which have been proven to possess beneficial effects in CVDs (9). Citrus aurantium L. , commonly known as bitter orange, is a flowering plant that belongs to the Rutaceae family of the Sapindales order. This species is widely distributed in tropical and subtropical southeast regions of the world. Its flowers and fruits are used for medicinal purposes, mainly as remedies for many disorders of the digestive system, as a cardiac tonic and for anxiety (10). The peel is often used in the formulation of herbal teas due to its flavor profiles, its digestive and carminative effects and for the production of stomachic and laxative products (11). However, citrus fruits Abstract In the present study, we aimed to examine the potential protective effect of C. aurantinum L. peel extract against oxidative damage induced by hexavalent chromium in the heart of adult rats. Rats were divided into six groups. Group I served as contro ls and received standard diet. Group II received via drinking water potassium dichromate (K2Cr2O7) alone (700 ppm) during 3 weeks. Groups III and IV were pre-treated for 10 days by gavage with the ethanolic extract of C. aurantium peels at doses of 100 and 300 mg/kg body weight/day, respectively, and then K2Cr2O7 was administrated during 3 weeks. Groups V and VI received by gavage only C. aurantium peel ethanolic extract at doses of 100 and 300 mg/kg body weight/day, respectively, during 10 days. K2Cr2O7 treatment increased the cardiac levels of malondialdehyde (MDA), protein carbonyls (PCO), advanced oxidation protein products (AOPP), non-protein thiols, glutathione and vitamin C, as well as the activities of catalase, superoxide dismutase and glutathione peroxidase. Cardiac histological alterations, manifested by hemorrhage and cytoplasmic vacuolization, were also observed. Pre-treatment with C. aurantium peel extract (300 mg/kg) attenuated significantly the biochemical and histopathological changes observed following K2Cr2O7 exposure in rat’s heart. Our findings indicated that C. aurantium peel extract was able to hamper K2Cr2O7-induced myocardial injury, which could be attributed to its antioxidant activity.