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Enhanced heat shock protein-70 (HSP-70) expression in the lungs is associated with attenuated acute lung injury (ALI) in a sepsis model. Chronic kidney disease (CKD) significantly contributes to the poor prognosis of patients with sepsis. This study examined the relationship between sepsis-induced ALI severity and altered lung HSP-70 expression in CKD. Experimental rats underwent a sham operation (control group) or 5/6 nephrectomy (CKD group). Sepsis was induced with cecal ligation and puncture (CLP). Laboratory tests and lung harvest were performed in the control group (without CLP and after 3, 12, 24, and 72 h of CLP) and in the CKD group (without CLP and after 72 h of CLP). ALI was the most severe after 12 h of sepsis. The mean lung injury score at 72 h after sepsis was significantly higher in the CKD group than in the control group (4.38 versus 3.30, p < 0.01). Nonetheless, enhanced lung HSP-70 expression was not observed in the CKD group. This study shows that altered lung HSP-70 expression is associated with the worsening of sepsis-induced ALI in patients with CKD. Enhancing lung HSP-70 is a novel treatment target for patients with CKD and sepsis-induced ALI. [ABSTRACT FROM AUTHOR]

Exposure to high ambient temperature is a stressor that influences both biological and behavioral functions and has been previously shown to have an extensive impact on brain structure and function. Physiological, cellular and behavioral responses to heat-stress (HS) (40–41 °C, 2 h) were evaluated in adult male Sprague-Dawley rats. The effect of HS exposure before predator-scent stress (PSS) exposure (i.e., HS preconditioning) was examined. Finally, a possible mechanism of HS-preconditioning to PSS was investigated. Immunohistochemical analyses of chosen cellular markers were performed in the hippocampus and in the hypothalamic paraventricular nucleus (PVN). Plasma corticosterone levels were evaluated, and the behavioral assessment included the elevated plus-maze (EPM) and the acoustic startle response (ASR) paradigms. Endogenous levels of heat shock protein (HSP)-70 were manipulated using an amino acid (L-glutamine) and a pharmacological agent (Doxazosin). A single exposure to an acute HS resulted in decreased body mass (BM), increased body temperature and increased corticosterone levels. Additionally, extensive cellular, but not behavioral changes were noted. HS-preconditioning provided behavioral resiliency to anxiety-like behavior associated with PSS, possibly through the induction of HSP-70. Targeting of HSP-70 is an attractive strategy for stress-related psychopathology treatment. [ABSTRACT FROM AUTHOR]

Growing evidences demonstrated that zinc oxide nanoparticles (ZnONPs) could reach the brain after oral ingestion; however, the “neurotoxicity of” ZnONPs after oral exposure has not been fully investigated. This study aimed to explore the “neurotoxicity of” ZnONPs (<100 nm) after oral exposure to two doses; 40 and 100 mg/kg for 24 h and 7 days. The exposure to 40 and 100 mg/kg of ZnONPs for 24 h did not elicit “neurotoxicity” compared to normal control. However, the daily exposure to both doses for 7 days caused oxidative stress in brain tissue as detected by the elevation of the levels of malondialdehyde, the main product of lipid peroxidation and nitrite as an index of nitric oxide with concomitant decline in the concentrations of antioxidants. In addition, both doses resulted in DNA fragmentation which was confirmed by increased percentage of tailed DNA, DNA tail intensity and length and tail moment particularly with the dose 100 mg/kg. Moreover, both doses led to the elevation of the inflammatory cytokines along with increased apoptotic markers including caspase-3 and Fas. Heat shock protein-70 levels were also elevated possibly as a compensatory mechanism to counteract the ZnONPs-induced oxidative stress and apoptosis. The present results indicate the “neurotoxicity of” ZnONPs after recurrent oral exposure via oxidative stress, genotoxicity, inflammatory response and apoptosis. [ABSTRACT FROM AUTHOR]