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

AbstractProjectBoth septic shock and sodium selenite (Na2SeO3) lead to multiple organ failure through oxidation. Na2SeO3 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 Na2SeO3 (5H2O·Na2SeO3) at oxidant doses.ProcedureIn a three-step study on 204 rats we: (i) observed toxic effects of Na2SeO3 injected intraperitoneously (IP) and determined its Minimum Dose Without Toxic effect (MDWT) 0.25–0.35mg/kg selenium (Se) content; (ii) injected IP LPS at 70% lethal dose (LD) followed, or not, one hour later by IP Na2SeO3 at MDWT and (iii) by doses>MDWT. At 48h, in survivors, we measured plasma creatinine, lactate, aspartate and alanine aminotransferase (AST, ALT), nitric oxide (NO) and Se concentrations.Results(i) Na2SeO3 alone did not increase NO and lactate. Encephalopathy appeared at 1mg Se/kg. Creatinine increased at 1–1.75mg Se/kg, AST, ALT at 3–4.5mg Se/kg, and the minimum LD was 3mg Se/kg. (ii) Mortality after LPS was 37/50 (74%, [62–86%]) vs. 20/30 (67%, [50–84%]) when followed by Na2SeO3 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 ≥0.6mg/kg (p