Effect of sodium butyrate on kidney and liver mitochondrial dysfunction in a lipopolysaccharide mouse model

Sodium butyrate can reduce inflammation, but it is not known if butyrate can improve mitochondrial dysfunction during sepsis. We tested butyrate to prevent or reverse lipopolysaccharide (LPS)-induced mitochondrial dysfunction in murine kidney and liver. C57BL/6 mice were grouped as control (n = 9), intraperitoneal (IP) LPS (n = 8), pretreatment with IP butyrate 600 (n = 3) or 1200 mg/kg (n = 8) followed 2 h later by LPS, posttreatment with IP butyrate 600 (n = 3) or 1200 mg/kg (n = 7) 1 h after LPS, or butyrate 1200 mg/kg only (n = 8). Kidney and liver tissue were collected at 24 h to measure mitochondrial respiration, electron transport system (ETS) complex activity and subunit expression, and content (citrate synthase [CS] activity and mtDNA/nDNA). Kidney mitochondrial respiration was decreased after LPS compared to controls. Pretreatment with butyrate 1200 mg/kg increased kidney OXPHOS_CI+II, ETS_CI+II, ETS_CII, and CIV respiration compared to LPS; posttreatment did not achieve significant increases except for OXPHOS_CI. Liver mitochondrial respiration exhibited a similar pattern as in kidney, but differences were not significant. ETS complex and CS activity did not differ between groups, but CI and CII subunit expression trended higher with butyrate in kidney. Changes in mtDNA/nDNA followed a similar pattern as respiration in kidney and liver with a decrease after LPS that was not present with butyrate pretreatment. These data show that butyrate can prevent-but not significantly reverse-the LPS-induced decrease in kidney mitochondrial respiration without a clear effect in liver. Mitochondrial protection was not attributable to changes in ETS complex activity but may reflect maintenance of ETS subunit expression.