Cerium Oxide Nanoparticles Attenuate Oxidative Stress and Inflammation in the Liver of Diethylnitrosamine-Treated Mice

Abstract

The catalytic activity of cerium oxide nanoparticles (CeO2NPs) is responsible for its application as an antitumor agent. This activity may be due to its ability to switch between III and IV oxidation states thereby conferring pro- and antioxidant properties. This study was designed to assess the hepatoprotective potential of CeO2NPs in male BALB/c mice administered diethylnitrosamine (DEN). Thirty-six mice were divided equally into six groups and treated intraperitoneally with normal saline (control), DEN (200 mg/kg) alone, CeO2NPs 1 (100 μg/kg) + DEN (200 mg/kg), CeO2NPs 2 (200 μg/kg) + DEN (200 mg/kg), CeO2NPs 1 alone, and CeO2NPs 2 alone. Animals were pretreated with CeO2NPs daily for eight consecutive days, while DEN was administered 48 h before the animals were sacrificed. Administration of DEN caused a significant increase in serum alanine aminotransferase (ALT) and urea by 51% and 96%, respectively. Markers of oxidative stress (malondialdehyde) and inflammation (nitric oxide and myeloperoxidase) in hepatic tissues of DEN-treated mice were increased by 60%, 16%, and 38%, respectively. The activities of hepatic superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, and level of reduced glutathione were significantly decreased in DEN-treated mice by 50%, 123%, 23%, 419%, and 78%, respectively. In addition, DEN increased the expression of hepatic Bcl₂ and COX-2, while p53, Bax, and iNOS were mildly expressed. Pretreatment with CeO2NPs attenuated the activities of antioxidant enzymes and expression of Bcl₂ and COX-2. Overall, CeO2NPs confers protection from DEN-induced liver damage via antioxidative activity.

Keywords: Cerium oxide; Hepatotoxicity; Inflammation; Nanoparticles; Oxidative stress.