ABSTRACT
Glycerol injection in rats can lead to rhabdomyolysis, with the release of the intracellular muscle content to the extracellular compartment and acute kidney injury (AKI). Oxidative stress and the inflammatory processes contribute to the disturbances in renal function and structure observed in this model. This study evaluated the effect of calcitriol administration in AKI induced by rhabdomyolysis and its relationship with oxidative damage and inflammatory process. Male Wistar Hannover rats were treated with calcitriol (6 ng/day) or vehicle (0.9% NaCl) for 7 days and were injected with 50% glycerol or saline 3 days after the beginning of calcitriol or saline administration. Four days after glycerol or saline injection, urine, plasma and renal tissue samples were collected for renal function and structural analysis. The oxidative stress and the inflammatory processes were also evaluated. Glycerol-injected rats presented increased sodium fractional excretion and decreased glomerular filtration rates. These alterations were associated with tubular injury in the renal cortex. These animals also presented increased oxidative damage, apoptosis, inflammation, higher urinary excretion of vitamin D-binding protein and decreased cubilin expression in renal tissue. All these alterations were less intense in calcitriol-treated animals. This effect was associated with decreases in oxidative damage and inflammation.
Subject(s)
Acute Kidney Injury/drug therapy , Acute Kidney Injury/etiology , Calcitriol/therapeutic use , Glycerol/pharmacology , Protective Agents/therapeutic use , Rhabdomyolysis/chemically induced , Rhabdomyolysis/complications , Acute Kidney Injury/blood , Acute Kidney Injury/urine , Animals , Apoptosis/drug effects , Calcitriol/pharmacology , Calcium/blood , Creatine Kinase/blood , Glomerular Filtration Rate/drug effects , Inflammation/drug therapy , Kidney Function Tests , Male , Oxidative Stress/drug effects , Protective Agents/pharmacology , Rats , Rats, Wistar , Vitamin D-Binding Protein/urineABSTRACT
A single injection of adriamycin (ADR) induces marked and persistent proteinuria in rats that progress to glomerular and tubulointerstitial lesions. It has been shown that ADR-induced nephrotoxicity is mediated, at least in part, by oxidative stress that lead to inflammation. Endogenous hydrogen sulfide (H2S) is synthesized from L-cysteine and is an important signaling molecule in inflammation. This study evaluates the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S formation, on the evolution of renal damage induced by ADR. The rats were injected i.p. with 0.15 M NaCl or PAG (50 mg/kg) 2 h after ADR injection (3.5 mg/kg). Control rats were injected with 0.15 M NaCl or PAG only. Twenty hours urine samples were collected for albuminuria and creatinine measurements on days 1 and 14 after saline or ADR injections and on days 2 and 15 blood samples were collected to measure plasma creatinine, then the rats were killed. The kidneys were removed for H2S formation evaluation, renal lipid peroxidation and glutathione levels, and histological and immunohistochemical analysis. On day 2 after ADR injection the rats presented increase in oxidative stress associated with neutrophils and macrophages influx in renal tissue. On day 15 the rats also presented increased desmin expression at glomerular edge and vimentin in cortical tubulointerstitium, as well as albuminuria. All these alterations were reduced by PAG injection. The protective effect of PAG on ADR nephrotoxicity was associated to decreased H2S formation and to restriction of oxidative stress and inflammation in the renal cortex.
