The ameliorative effect of cerium oxide nanoparticles on chlorpyrifos induced hepatotoxicity in a rat model: Biochemical, molecular and immunohistochemical study

Abstract

Background: Chlorpyrifos (CPF) is a widely used insecticide that causes toxicity to living organisms through the production of free radicals. Cerium oxide nanoparticles (CeO₂NPs) are a new antioxidant agent that has proved therapeutic effects. We evaluated the effect of CeO₂NPs on CPF hepatotoxicity.

Methods: Forty rats were randomized into four groups. Group I: rats received 1 ml corn oil by gastric tube once daily and 0.5 ml PBS by intra-peritoneal injection twice a week for 4 weeks. Group II: received CeO₂NPs 0.5 mg/kg in PBS by i.p. injection, twice weekly for four weeks. Group III: were treated with oral administration of CPF 13.5 mg/kg in corn oil daily for 4 weeks. Group IV: received CPF as in group III, then each animal received CeO₂NPs twice weekly for four weeks as in group II. Twenty-four hours after the last dose, rats were anesthetized and sera were collected for liver enzymes assessment. Afterwards, rats were sacrificed, livers were excised, the right lobe of each liver was fixed for immunohistochemical studies, and the left lobe was homogenized for oxidative profile assessment and molecular analysis.

Results: CPF group showed significant increase in liver transaminases, disturbance of the oxidative profile with up-regulation of BAX expression and down-regulation in the Bcl-2, Gadd45 and NFE2L2. CPF caused severe histopathological liver damage as well as significant increase in anti-Caspase 3 and TNF immunostaining. The CeO₂NPs treated group revealed significant improvement of all previous parameters.

Conclusion: CeO₂NPs could alleviate CPF hepatoxicity through decreasing expression of the inflammatory and apoptotic proteins and increasing the activity of antioxidant enzymes.

Keywords: Apoptosis; CeO2NPs; Chlorpyrifos; Hepatotoxicity; Oxidative stress.