Comprehensive study of dexamethasone on albumin biogenesis during normal and pathological renal conditions

Abstract

Context Dexamethasone (DXM) has an anti-immunoinflammatory effect, and is often used in acute kidney injury (AKI). However, the effects of DXM on albumin (ALB) have not been fully studied. Objective To investigate the effects of DXM on ALB production and renal function. Materials and methods Male Wistar rats were divided into normal and DXM groups (0.25, 0.5, 1 mg/kg for 5 days) (n = 15) for a dose-dependent study. Rats were divided into normal group and DXM groups (0.5 mg/kg for 3, 5, 7 days) (n = 9) for a time-dependent study. In AKI experiment, rats were divided into normal (saline), cisplatin (CP, 5 mg/kg, i.v.), CP + DXM groups (0.25, 0.5 and 1 mg/kg, i.m.) (n = 16). The blood and the organs were isolated for analysis. Results In normal, serum ALB (sALB) and serum total protein (sTP) increased in DXM group with sALB increased 19.8–32.2% (from small to large dosages); and 30.2–32.5.6% (from 3 to 7 days of DXM); sTP 15.7–22.6% and 14.2–24.3%; urine ALB (uALB) 31.5–392.3%, and 1047.2–1390.8%; urine TP (uTP) 0.68–173.1% and 98.0–504.9%, compared with normal groups. DXM increased the mRNA expression of Cebp and Hnf, suppressing podocin. In AKI, DXM decreased serum BUN (53.7%), serum Cre (73.4%), sALB (30.0%), sTP (18.7%), uALB (74.5%), uTP (449.3%), rescuing the suppressed podocin in kidney. Conclusions DXM acts on Cebp and Hnf and promotes ALB production. This finding helps to evaluate the rationale of DXM for kidney injury.

Keywords

• cisplatin
• acute kidney injury
• proteinuria
• gene transcription start site