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Nanoparticles have a promising future in biomedical applications and knowing whether they affect ex vivo vascular reactivity is a necessary step before their use in patients. In this study, we have evaluated the vascular effect of cerium dioxide nanoparticles (CeO 2 NPs) on the human saphenous vein in response to relaxing and contractile agonists. In addition, we have measured the protein expression of key enzymes related to vascular homeostasis and oxidative stress. We found that CeO 2 NPs increased expression of both SOD isoforms, and the consequent reduction of superoxide anion would enhance the bioavailability of NO explaining the increased vascular sensitivity to sodium nitroprusside in the presence of CeO 2 NPs. The NOX4 reduction induced by CeO 2 NPs may lead to lower H 2 O 2 synthesis associated with vasodilation through potassium channels explaining the lower vasodilation to bradykinin. In addition, we showed for the first time, that CeO 2 NPs increase the expression of ACE2 in human saphenous vein, and it may be the cause of the reduced contraction to angiotensin II. Moreover, we ruled out that CeO 2 NPs have effect on the protein expression of eNOS, sGC, BKca channels and angiotensin II receptors or modify the vascular response to noradrenaline, endothelin-1 and TXA 2 analogue. In conclusion, CeO 2 NPs show antioxidant properties, and together with their vascular effect, they could be postulated as adjuvants for the treatment of cardiovascular diseases. HSV: human saphenous vein; Bk: bradykinin, SNP: sodium nitroprusside; Ang II: angiotensin II; SOD: superoxide dismutase; NOX4: NAPH oxidase 4; ACE2: angiotensin-converting enzyme 2; eNOS: endothelial nitric oxide synthase; EC: endothelial cell; BKca: large conductance calcium activated potassium channel. [Display omitted] • CeO 2 NPs increase SOD1 and SOD2 and decrease NOX4 protein expression. • CeO 2 NPs increase NO mediated vasodilation. • CeO 2 NPs decrease bradykinin-induced vasodilation. • CeO 2 NPs increase the ACE2 protein expression in human saphenous vein. • CeO 2 NPs decrease vasoconstrictor effect to angiotensin II. [ABSTRACT FROM AUTHOR]

Chlorpyrifos (CPF) is a widely used insecticide that causes toxicity to living organisms through the production of free radicals. Cerium oxide nanoparticles (CeO 2 NPs) are a new antioxidant agent that has proved therapeutic effects. We evaluated the effect of CeO 2 NPs on CPF hepatotoxicity. 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 CeO 2 NPs 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 CeO 2 NPs 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. 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 CeO 2 NPs treated group revealed significant improvement of all previous parameters. CeO 2 NPs could alleviate CPF hepatoxicity through decreasing expression of the inflammatory and apoptotic proteins and increasing the activity of antioxidant enzymes. [Display omitted] • Chronic exposure to Chlorpyrifos (CPF) induced hepatotoxicity in rats. • CPF induced up-regulation of inflammatory markers and apoptotic markers. • Cerium oxide nanoparticles (CeO 2 NPs) could alleviate CPF- induced hepatoxicity. • CeO 2 NPs cause down-regulation of anti-oxidative (SOD, CAT and NFE2L2) markers. • CeO 2 NPs cause down-regulation of anti-apoptotic (Bcl 2 & Gadd45) markers. [ABSTRACT FROM AUTHOR]

Cerium oxide nanoparticles (CeO2NPs) is an efficient neuroprotective agent and showed promising effects in some neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis. However, the implication of CeO2NPs in Parkinsonism remains to be investigated. The aim of this study was to assess the possible role of CeO2NPs as a neuroprotective agent against the development of behavioral and biochemical changes in rat model of Parkinson’s disease. Thirty rats were included and received left intrastriatal injection of either saline (controls, n = 10) or 6-hydroxy dopamine (6-OHDA) in untreated group (n = 10) and 10 rats were received intraperitoneal injection of low dose CeO2NPs two hours before surgery, and continued once daily for 6 weeks (preventive group). At the end of experimental period, rats were subjected to behavioral assessment and then killed for biochemical analysis of striatal dopamine levels, oxidative stress markers and caspase-3 activity. Results showed that CeO2NPs resulted in partial neuroprotection against disturbances in motor performance. It also partially decreased apoptosis and oxidative stress in preventive group, while it failed to increase striatal dopamine level as compared to untreated rats. The present study verified some neuroprotective effects of CeO2NPs in 6-OHDA-induced Parkinsonian rats through their antioxidant and anti apoptotic effects. Some of these effects persisted till the end of six weeks whereas others declined after three weeks. A larger dose may be needed to produce more valuable effects and to maintain protection for a longer period.