Intravenous Vitamin C attenuates hemorrhagic shock-related renal injury through the induction of SIRT1 in rats

Highlights: • Intravenous vitamin c attenuates HS related renal injury via the Induction of SIRT1. • NF-Kb and HO-1 could be the downstream of SIRT1. • There were no differences in the effects between the high and low dose of Vitamin C. To investigate the effect of intravenous Vitamin C (VC) on hemorrhagic shock (HS)-associated rat renal injury and the involved mechanism. Thirty SD rats were randomly assigned to the sham surgery (sham), hemorrhagic shock (HS), HS+100 mg/kg VC (H + VL), HS+500 mg/kg VC (H + VH) and HS+100 mg/kg VC + EX527 (H + VL + E) groups. Tissue and blood samples were collected 6 h after surgery. Kidney pathological changes were scored. Creatinine (CRE), blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) levels in serum and Vitamin C levels and superoxide dismutase (SOD) activity and the ability to suppress hydroxyl radical (RAFHR) in plasma were measured. The expression of Sirtuin1 (SIRT1), Acetyl-NF-κB (Ace-NF-κB), heme oxygenase-1 (HO-1), TNF-α, and IL-1β in tissues was analyzed by ELISA or western-blot. In the HS group, the kidney pathological score and CRE, BUN, TNF-α, and IL-1β levels in serum were significantly higher than in the Sham group (P P P P P P 0.05). Additionally, MDA, TNF-α, IL-1β and Acetyl-NF-κB expression levels were decreased in the kidney (P < 0.05), while SOD, SIRT1 and HO-1 levels were notably enhanced. There were no differences between the H + VL and H + VH groups aside from plasma Vitamin C levels. The effect of Vitamin C was decreased after the addition of EX527, which inhibits SIRT1. Intravenous Vitamin C might attenuate HS-related renal injury via the SIRT1 pathway, and it appears that there were no differences in the effects between the high and low doses.