Elements of margin of safety, toxicity and action of sodium selenite in a lipopolysaccharide rat model

Abstract Project Both septic shock and sodium selenite (Na 2 SeO 3 ) lead to multiple organ failure through oxidation. Na 2 SeO 3 has direct oxidant effects above the nutritional level and indirect anti-oxidant properties. In a lipopolysaccharide (LPS) rat model we assessed margin of safety, toxicity and beneficial effect of pentahydrate Na 2 SeO 3 (5H 2 O·Na 2 SeO 3 ) at oxidant doses. Procedure In a three-step study on 204 rats we: (i) observed toxic effects of Na 2 SeO 3 injected intraperitoneously (IP) and determined its Minimum Dose Without Toxic effect (MDWT) 0.25–0.35 mg/kg selenium (Se) content; (ii) injected IP LPS at 70% lethal dose (LD) followed, or not, one hour later by IP Na 2 SeO 3 at MDWT and (iii) by doses > MDWT. At 48 h, in survivors, we measured plasma creatinine, lactate, aspartate and alanine aminotransferase (AST, ALT), nitric oxide (NO) and Se concentrations. Results (i) Na 2 SeO 3 alone did not increase NO and lactate. Encephalopathy appeared at 1 mg Se/kg. Creatinine increased at 1–1.75 mg Se/kg, AST, ALT at 3–4.5 mg Se/kg, and the minimum LD was 3 mg Se/kg. (ii) Mortality after LPS was 37/50 (74%, [62–86%]) vs. 20/30 (67%, [50–84%]) when followed by Na 2 SeO 3 at MDWT ( p  = 0.483) with a decreased in NO (−31%, p  = 0.038) a trend for lactate decrease (−19%, p  = 0.068) and an increased Se in plasma of survivals. (iii) All rats died at doses ≥0.6 mg/kg ( p Conclusion Mechanisms of LPS and Na 2 SeO 3 toxicity differ (i.e. NO, lactate). In septic shock 5H 2 O·Na 2 SeO 3 toxicity increased, margin of safety decrease, but IP administration of dose considered as oxidant of 5H 2 O·Na 2 SeO 3 showed beneficial effects.