Intra-abdominal infection or peritonitis is a cause for great concern due to high mortality rates. The prognosis of severe intra-abdominal infection is significantly diminished in the presence of acute kidney injury (AKI) which is often characterized by renal tubular cell death that can lead to renal failure. The purpose of the current study is to examine the therapeutic efficacy of cerium oxide (CeO2) nanoparticles for the treatment of peritonitis-induced AKI by polymicrobial insult. A one-time administration of CeO2 nanoparticles (0.5 mg/kg) in the absence of antibiotics or other supportive care, attenuated peritonitis-induced tubular dilatation and the loss of brush border in male Sprague–Dawley rats. These improvements in renal structure were accompanied by decreases in serum cystatin-C levels, reduced renal oxidative stress, diminished Stat-3 phosphorylation and an attenuation of caspase-3 cleavage suggesting that the nanoparticle treatment improved renal glomerular filtration rate, diminished renal inflammation and reduced renal apoptosis. Consistent with these data, further analysis demonstrated that the CeO2 nanoparticle treatment diminished peritonitis-induced increases in serum kidney injury molecule-1 (KIM-1), osteopontin, β-2 microglobulin and vascular endothelial growth factor-A (VEGF-A) levels. In addition, the nanoparticle attenuated peritonitis-induced hyperglycemia along with increases in blood urea nitrogen (BUN), serum potassium and sodium. CeO2 nanoparticles scavenge reactive oxygen species and attenuate polymicrobial insult induced increase in inflammatory mediators and subsequent AKI. Taken together, the data indicate that CeO2 nanoparticles may be useful as an alternative therapeutic agent or in conjunction with standard medical care for the treatment of peritonitis induced acute kidney injury.

Introduction Empagliflozin, a known inhibitor of sodium-glucose cotransporter type 2 (SGLT2) decreases glucose reabsorption by the renal tubules and promotes glucose excretion into the urine. While the effectiveness of Empagliflozin in the management of hyperglycemia along with associated cardiovascular and all-cause mortality has been demonstrated previously, the therapeutic benefits associated with the long-term use of this drug in obese animals have yet to be investigated. Methods Male 5-week-old lean and obese Zucker rats were randomly assigned to one of the 4 groups- lean control, lean treated, obese control, obese treated and treated with either Empagliflozin (10 mg/kg BW / day) or placebo for 25 weeks to investigate the therapeutic effect of Empagliflozin. Results Empagliflozin treatment in the obese animals was associated with decreased body weight, attenuated the loss of F-actin from the renal tubules and improved renal structure and function. These changes in renal function were associated with significant improvements in the glucose tolerance, and decreased non-fasting circulatory levels of glucose, amylase, and other inflammatory markers including NGAL, cystatin C, and clusterin. Conclusion Long-term use of Empagliflozin in diabetic obese Zucker rats is associated with improvements in glucose tolerance and decreased loss of renal structure and function.