Comparación de la concentración urinaria de orto-cresol y de ácido hipúrico como biomarcadores de exposición laboral a tolueno / Comparison of urinary concentration of ortocresol and hippuric acid as biomarkers of occupational exposure to toluene

La exposición a tolueno en ambientes laborales puede ser biomonitoreada a través de la concentración de ácido hipúrico en orina. Sin embargo, se sabe que este metabolito puede provenir de fuentes distintas al tolueno, pudiendo causar errores en la estimación de la exposición a tolueno. En este estudio, se compararon los niveles de ácido hipúrico urinario con los de otro metabolito del tolueno, el orto-cresol, con el fin de establecer si éste último es mejor biomarcador de exposición. Se cuantificaron ambos biomarcadores por la técnica de HPLC en muestras de trabajadores de empresas que utilizan tolueno y de personas no expuestas. La validación de la metodología analítica demostró la inestabilidad del ácido hipúrico y que su ensayo de cuantificación no es robusto. La concentración de ácido hipúrico urinaria tuvo una gran variabilidad en las muestras tanto de trabajadores expuestos como del grupo control así como una falta de relación con la concentración ambiental de tolueno, lo que no le permite cumplir con los requerimientos de un biomarcador. Por otro lado, orto-cresol demostró especificidad y menor variabilidad interindividual. Se propone que orto-cresol es una mejor alternativa para el biomonitoreo de exposición laboral a tolueno evitando los falsos positivos que se puedan generar en el biomonitoreo por ácido hipúrico (AU)

Comparison of urinary concentration of ortocresol and hippuric acid as biomarkers of occupational exposure to toluene Occupational exposure to toluene may be evaluated by the quantification of hippuric acid in urine. However, this metabolite is not exclusive to toluene which may lead to bias in exposure assessment. In this study, urinary hippuric acid was compared to urinary ortho-cresol, another toluene metabolite to assess if the latter is a better biomarker of exposure to the solvent. Urine samples from workers exposed to toluene and from a control population were collected and both metabolites were quantified by HPLC. Validation of analytical methods showed that hippuric acid is unstable and that the analytical assay is not robust. Hippuric acid had highly variable concentrations in both workers and control population and was not related to environmental concentrations of the solvent, showing its limited validity as a biomarker. Ortho-cresol, on the other hand, showed specificity and less variability among the individuals tested. We propose that ortho-cresol is a better predictor of occupational exposure to toluene and that it may be used to avoid false positive determinations when hippuric acid is used as biomarker (AU)

The effect of aliskiren on urinary cytokine/chemokine responses to clamped hyperglycaemia in type 1 diabetes.

AIMS/HYPOTHESIS: Acute clamped hyperglycaemia activates the renin-angiotensin-aldosterone system (RAAS) and increases the urinary excretion of inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes mellitus. Our objective was to determine whether blockade of the RAAS would blunt the effect of acute hyperglycaemia on urinary cytokine/chemokine excretion, thereby giving insights into potentially protective effects of these agents prior to the onset of clinical nephropathy. METHODS: Blood pressure, renal haemodynamic function (inulin and para-aminohippurate clearances) and urinary cytokines/chemokines were measured after 6 h of clamped euglycaemia (4-6 mmol/l) and hyperglycaemia (9-11 mmol/l) on two consecutive days in patients with type 1 diabetes mellitus (n = 27) without overt nephropathy. Measurements were repeated after treatment with aliskiren (300 mg daily) for 30 days. RESULTS: Before aliskiren, clamped hyperglycaemia increased filtration fraction (from 0.188 ± 0.007 to 0.206 ± 0.007, p = 0.003) and urinary fibroblast growth factor-2 (FGF2), IFN-α2 and macrophage-derived chemokine (MDC) (p < 0.005). After aliskiren, the filtration fraction response to hyperglycaemia was abolished, resulting in a lower filtration fraction after aliskiren under clamped hyperglycaemic conditions (p = 0.004), and none of the biomarkers increased in response to hyperglycaemia. Aliskiren therapy also reduced levels of urinary eotaxin, FGF2, IFN-α2, IL-2 and MDC during clamped hyperglycaemia (p < 0.005). CONCLUSIONS/INTERPRETATION: The increased urinary excretion of inflammatory cytokines/chemokines in response to acute hyperglycaemia is blunted by RAAS blockade in humans with uncomplicated type 1 diabetes mellitus.

Drugs interacting with organic anion transporter-1 affect uptake of Tc-99m-mercaptoacetyl-triglycine (MAG3) in the human kidney: therapeutic drug interaction in Tc-99m-MAG3 diagnosis of renal function and possible application of Tc-99m-MAG3 for drug development.

INTRODUCTION: Renal uptake of Tc-99m-MG3 involves organic anion transporter (OAT). Treatment with drugs showing OAT affinity might interfere with renal uptake of Tc-99m-MAG3, leading to misinterpretation in Tc-99m-MAG3. This study was conducted to discuss a possible drug interference with Tc-99m-MAG3 diagnosis on OAT sites. METHODS: Renal uptake and plasma clearance of Tc-99m-MAG3 were analyzed in healthy volunteers under control and OAT1 and OAT3 related drug treatment conditions. An in vitro uptake study using OAT1 or OAT3 expressing cells was also conducted. RESULTS: Both PAH and probenecid treatment induced delays in Tc-99m-MAG3 clearance from blood, and reductions in the renal uptake clearance. As a result, the normalized effective renal plasma flow estimated from Tc-99m-MAG3 clearance was significantly underestimated, whereas the glomerular filtration rate estimated from plasma creatinine levels was unchanged. The transport activity of Tc-99m-MAG3 was higher in OAT1-expressing cells than in OAT3-expressing cells. CONCLUSION: Drugs with OAT1 affinity affect the renal uptake of Tc-99m-MAG3 and blood clearance. This might cause misinterpretation of functional diagnosis of the kidney using Tc-99m-MAG3.

Cisplatin: nephrotoxic action in vertebrates and its prevention.

1. The kidney of frog and black sculpin appeared to be much less sensitive to the toxic action of CP in comparison with rat and pigeon. 2. The impairment of renal function after CP administration resulted in increased serum urea in rat, uric acid in pigeon and magnesium in black sculpin. 3. Kidney swelling is important feature of CP nephrotoxicity in rat and pigeon but not in frog and fish. 4. Pretreatment with choline chloride, PAH, furosemide and ethacrynic acid reduced the nephrotoxic action of CP in rat but did not prevent the accumulation of platinum in renal tissue which appeared to be a function of the dose injected to investigated animals.