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Therapeutic efficacy of cerium oxide nanoparticles in treatment of sepsis induced renal failure (LB608)
Author(s) -
Manne Nandini,
Arvapalli Ravikumar,
Nepal Niraj,
Nandyala Geeta,
Rice Kevin,
Shinichi Asano,
Blough Eric
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb608
Subject(s) - sepsis , inflammation , reactive oxygen species , cerium oxide , pharmacology , renal function , medicine , chemistry , biochemistry , catalysis
Severe sepsis is a complex disease of multifactorial etiology that is characterized by systemic inflammation which can rapidly progress to multi‐organ dysfunction and death. Although most of the deaths due to sepsis are related to the release of inflammatory mediators, treatments to date have largely centered on the administration of antibiotics, i.v. fluids, NSAIDS, and vasopressors. Studies have shown that the release of inflammatory mediators is mediated, at least in part, through the generation of reactive oxygen species (ROS). Other work has shown that cerium oxide (CeO 2 ) nanoparticles can function to scavenge ROS and that these particles exhibit anti‐bacterial activity. On the basis of these data, we hypothesized a CeO 2 nanoparticle based treatment strategy would diminish sepsis‐induced mortality, sepsis‐associated inflammation and that these improvements would be associated with improved renal function. Male Sprague Dawley rats were subjected to polymicrobial sepsis and treated with 0.5mg/kg of CeO 2 nanoparticles intravenously. Our preliminary data suggests that the CeO 2 nanoparticle intervention improved animal survivability and promoted the restoration of core body temperature. Changes in survivability and thermoregulation were associated with an attenuation in the sepsis‐induced release of β2 microglobulin, cystatin, gluthatione‐s transferase alpha, gluthatione‐s transferase mu, kidney injury molecule‐1, osteopontin and a reduction in serum total ROS. Histological analysis demonstrated that CeO 2 nanoparticles decreased sepsis‐induced proximal tubular dilatation and loss of brush border. Taken together, these data suggest that CeO 2 nanoparticle based interventions may exhibit potential for the treatment of sepsis‐induced renal failure and death. Grant Funding Source : This work was supported in part from DOE grant (DE‐PS02‐09ER‐01 to E.R.B)