Anti-apoptotic and Antioxidant Effect of Cerium Oxide Nanoparticles on Cyclophosphamide-Induced Hepatotoxicity

Abstract

Objective: Cyclophosphamide (CP), as an anticancer agent has side effects, especially hepatotoxicity. Cerium oxide nanoparticles [nanoceria (NC)], which act as antioxidants, have a protective effect against oxidative stress-induced toxicity. This study evaluated the preventive effect of NC in hepatotoxicity induced by CP. Materials and Methods: Thirty-two mice were randomly distributed into four groups: control (received only normal saline), NC (received NC 100 μg/kg for 3 days, intraperitoneally), CP (received CP 200 mg/kg single dose on the third day of the study, intraperitoneally), and NC+CP (NC 100 μg/kg and CP 200 mg/kg). Two days after the final treatment, oxidative stress marker (MDA and GSH) and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels were measured, and histopathological and immunohistochemical examinations were performed for determining the effects of NC on hepatotoxicity. Results: CP-induced hepatotoxicity was evident by the significant elevation of liver enzyme levels and alteration in oxidative stress marker levels. Additionally, histopathological changes and apoptosis were markedly increased. NC decreased MDA level, increased GSH level and decreased liver enzyme levels in CP-treated mice. In addition, NC pretreatment could be alleviated by the immunoreactivity of caspase-3 in CP-treated mice compared with the CP group. Conclusion: NC showed a potent antioxidant effect in hepatotoxicity induced by CP. The study suggested that NC through its antioxidant and anti-apoptotic properties has a protective effect against hepatotoxicity induced by CP.

The potential ameliorative impacts of cerium oxide nanoparticles against fipronil-induced hepatic steatosis

“…The efficiency of CeNPs on liver tissues was demonstrated by restoring the tissues architecture; necrosis, inflammation, and a decline of dystrophy in rats exposed to the FIP corroborated the histopathological lesions observed in the study 84 . FIP group revealing congested central vein, massive fatty degeneration in the periportal areas, lymphocytic aggregation in between massive fatty degeneration, with lymphocytic infiltration.…”

Protective Effects of Evening Primrose Oil against Cyclophosphamide-Induced Biochemical, Histopathological, and Genotoxic Alterations in Mice

“…Acrolein is a reactive aldehyde that generates toxic reactive oxygen species (ROS), leading to oxidative stress [5]. Cyclophosphamide toxicity affects many organs, including the liver and pancreas, and is characterized by depletion of glutathione, lipid peroxidation, altered DNA profile, pro-inflammatory response, and apoptosis [6,7].…”

Modulation of monosodium glutamate induced histological injuries, histomorphometrical alterations and DNA damage in the mice hepatic and renal tissues by oral administration Nano-cerium oxide and L-arginine and their combination

“…Pretreatment with Cerium oxide nanoparticle could be alleviated the immunoreactivity of caspase-3 in cyclophosphamide-treated mice as recorded by Amiri, et al, [57] ,. Safety of cerium oxide nanoparticle application in medical applications were investigated in cellular function by Niu et al, [20] Bagher et al, [58] .…”

“…Moreover, Srinivas et al [27] also stated that cerium oxide nanoparticles did not cause any unsafe effects on hepatic and renal functions as well as hematology in rats treated with cerium oxide at14-day. Likewise, Amiri, et al, [28] cerium oxide nanoparticle at dose 100 μg/kg for 3 days, intraperitoneally decline malondialdehyde level, elevate GSH level and decreased hepatic enzyme levels in Cyclophosphamide-treated mice. He reported also that cerium oxide nanoparticle pretreatment could be alleviated the immunoreactivity of caspase-3 in cyclophosphamide -treated mice compared with the Cyclophosphamide group.…”