Free p-Cresol Alters Neutrophil Function in Dogs.
To achieve a clearer understanding of the mechanisms responsible for neutrophil dysfunction recently described in dogs with chronic renal failure (CRF), the plasma concentrations of free p-cresol in healthy dogs (n = 20) and those with CRF (n = 20) were compared. The degree of correlation was determined between plasma levels of p-cresol and markers of oxidative stress and function of neutrophils in these dogs. The effect of this compound on oxidative metabolism and apoptosis was assessed in neutrophils isolated from 16 healthy dogs incubated in RPMI 1640 supplemented with p-cresol (0.405 mg/L) and compared with medium supplemented with uremic plasma (50%). To achieve this, the plasma concentration of p-cresol was quantified by liquid phase high-performance liquid chromatography. The neutrophil oxidative metabolism was determined using the probes hydroethidine and 2',7'-dichlorofluorescein diacetate and apoptosis was measured using Annexin V-PE by capillary flow cytometry. Compared with the healthy dogs, uremic dogs presented higher concentrations of free p-cresol, greater oxidative stress, and neutrophils primed for accelerated apoptosis. The free p-cresol induced in neutrophils from healthy dogs increased apoptosis and decreased reactive oxygen species production. We conclude that the health status presented during uremia concomitant with the increase in plasma free p-cresol can contribute to the presence of immunosuppression in dogs with CRF.
Department of Clinical, Surgery and Animal Reproduction, College of Veterinary Medicine of Araçatuba.
Anelise Maria
AM
Bosco
Department of Clinical, Surgery and Animal Reproduction, College of Veterinary Medicine of Araçatuba.
Priscila Preve
PP
Pereira
Department of Clinical, Surgery and Animal Reproduction, College of Veterinary Medicine of Araçatuba.
Breno Fernando Martins
BF
Almeida
Department of Clinical, Surgery and Animal Reproduction, College of Veterinary Medicine of Araçatuba.
Luis Gustavo
LG
Narciso
Department of Molecular Chemistry and Physics, São Paulo State University, Araçatuba, Brazil.
Diego Borba
DB
Dos Santos
Department of Molecular Chemistry and Physics, São Paulo State University, Araçatuba, Brazil.
Álvaro José Dos
ÁJ
Santos-Neto
Department of Clinical, Surgery and Animal Reproduction, College of Veterinary Medicine of Araçatuba.
Wagner Luis
WL
Ferreira
Department of Clinical, Surgery and Animal Reproduction, College of Veterinary Medicine of Araçatuba.
Paulo César
PC
Ciarlini
D000818:Animals; D017209:Apoptosis; D003408:Cresols / Q000097:blood* / Q000378:metabolism; D004285:Dogs; D005260:Female; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D014511:Uremia / Q000097:blood / Q000378:metabolism / Q000473:pathology
D003408:Cresols; C032538:4-cresol
Apoptosis; Chronic renal failure; P-cresol; Respiratory burst; Superoxide; Uremia