Estado de los marcadores de fase aguda y estrés oxidativo en los enfermos con litiasis de la vía urinaria / State of acute phase markers and oxidative stress in patients with kidney stones in the urinary tract

Objetivo: El objetivo del presente estudio es evaluar el estado de los marcadores de fase aguda y de estrés oxidativo en enfermos con litiasis renal. Material y métodos: Estudio prospectivo en enfermos con litiasis renal. Se incluyeron100 enfermos y 25 controles sanos. Se evaluaron como marcadores de fase aguda: albúmina, beta2 microglobulina, gamma-glutamil transpepsidasa, lactato deshidrogenasa, factor de necrosistumoral alfa, interleucina 1 e interleucina 6 y como marcadores de estrés oxidativo los niveles de lipoperóxidos, superóxido dismutasa y glutatión peroxidasa. Resultados: En los enfermos estudiados se apreció un incremento de los marcadores de daño celular renal expresado por la beta2 microglobulina (p = 0,04), albúmina (p = 0,004), lactato deshidrogenasa (p = 0,001), así como gamma-glutamil transpepsidasa (p = 0,01). Existió una correlación directa entre los niveles de beta2 microglobulina con el tamaño de la litiasis (r = 0,3; p = 0,03). La asociación entre la extensión del cálculo y la activación de las citoquinas se apreció de forma más intensa en los enfermos con cálculos coraliformes en los que las cifras de factor de necrosis tumoral alfa (p = 0,011), interleucina 1 (p = 0,004) e interleucina 6 (p = 0,004) fueron significativamente mayores. Los enfermos con litiasis de la vía urinaria presentaron cifras significativamente elevadas de radicales libres en plasma, expresados como lipoperóxidos (p = 0,03), que se acompañaron de un descenso en la actividad de las enzimas antioxidantes superóxido dismutasa (p = 0.03) y glutatión peroxidasa (p = 0,002). Conclusiones: Los pacientes con litiasis urinaria presentan una elevación de los marcadores de fase aguda, asociada a un incremento de especies reactivas del oxígeno y un descenso en la actividad de las enzimas antioxidantes (AU)

Objective: This present study has aimed to assess the state of acute phase markers and oxidative stress in patients with kidney stones. Material and methods: A prospective study was carried out on 100 patients with kidney stones and 25 healthy controls. Albumin, beta2 microglobulin, Gamma-glutamyl transpepsidase, Lactatede hydrogenase, Tumor necrosis factor alpha, Interleukin 1 and Interleukin-6 were evaluated as acute phase markers and lipid peroxidation products, Superoxide dismutase and Glutathione peroxidase levels acted as oxidative stress markers. Results: An increase in renal cell damage markers as expressed by the beta2 microglobulin (p = 0.04), albumin (p = 0.004), Lactate dehydrogenase (p = 0.001) and Gamma glutamyl transpepsidasa (p = 0.01) was observed in the patient group. There was a direct correlation between levels of beta2 microglobulin and stone size (r = 0.3, p = 0.03). The association between stone size and cytokine activation was observed to be stronger in patients with staghorn calculi. In these patients, Tumor necrosis factor alpha (p = 0.011), Interleukin 1 (p = 0.004) and Interleukin6 (p = 0.004) were significantly higher. Patients with stones in the urinary tract showed data of significantly higher oxidative stress, expressed as an increase in levels of lipid peroxidation products (p = 0.03) and a decrease in the antioxidant activity of Superoxide dismutase (p = 0.03)and Glutathione peroxidase (p = 0.002).Conclusions: Patients undergoing urolithiasis showed an elevation of acute phase markers, associated with oxidative stress as expressed by an increase in lipid peroxidation products and a decrease in the antioxidant enzyme activity (AU)

[State of acute phase markers and oxidative stress in patients with kidney stones in the urinary tract]. / Estado de los marcadores de fase aguda y estrés oxidativo en los enfermos con litiasis de la vía urinaria.

OBJECTIVE: This present study has aimed to assess the state of acute phase markers and oxidative stress in patients with kidney stones. MATERIAL AND METHODS: A prospective study was carried out on 100 patients with kidney stones and 25 healthy controls. Albumin, ß2 microglobulin, Gamma-glutamyl transpepsidase, Lactate dehydrogenase, Tumor necrosis factor alpha, Interleukin 1 and Interleukin-6 were evaluated as acute phase markers and lipid peroxidation products, Superoxide dismutase and Glutathione peroxidase levels acted as oxidative stress markers. RESULTS: An increase in renal cell damage markers as expressed by the ß2 microglobulin (p=0.04), albumin (p=0.004), Lactate dehydrogenase (p=0.001) and Gamma glutamyl transpepsidasa (p=0.01) was observed in the patient group. There was a direct correlation between levels of ß2 microglobulin and stone size (r=0.3, p=0.03). The association between stone size and cytokine activation was observed to be stronger in patients with staghorn calculi. In these patients, Tumor necrosis factor alpha (p=0.011), Interleukin 1 (p=0.004) and Interleukin 6 (p=0.004) were significantly higher. Patients with stones in the urinary tract showed data of significantly higher oxidative stress, expressed as an increase in levels of lipid peroxidation products (p=0.03) and a decrease in the antioxidant activity of Superoxide dismutase (p=0.03) and Glutathione peroxidase (p=0.002). CONCLUSIONS: Patients undergoing urolithiasis showed an elevation of acute phase markers, associated with oxidative stress as expressed by an increase in lipid peroxidation products and a decrease in the antioxidant enzyme activity.

Differential effects of cytokines on the inducible expression of CYP1A1, CYP1A2, and CYP3A4 in human hepatocytes in primary culture.

We have investigated the effect of cytokines, including interleukin-6 (Il-6), interleukin-1 alpha (Il-1 alpha), and tumor necrosis factor-alpha (TNF-alpha), on the inducible expression of cytochrome P450s (CYP) CYP1A1, CYP1A2, and CYP3A4 in human hepatocytes in primary culture. The ability of these cultures to mimic the acute phase response when stimulated with cytokines was evaluated using immunoblotting to measure the production of albumin, ferritin, fibrinogen, and ceruloplasmin. The cytokines exhibited specific patterns of action on the production of these proteins. Albumin was depressed by all the cytokines. In contrast to Il-6 and Il-1 alpha, TNF-alpha reduced the production of fibrinogen and ceruloplasmin but stimulated the production of ferritin. When cells were treated with the CYP inducer alone, large increases in the expression of CYP1A1 and CYP1A2 by beta-naphthoflavone and of CYP3A4 by rifampicin were observed at messenger RNA (mRNA) and protein levels, by ribonuclease protection and immunoblotting, respectively. When the cells were treated with the inducer plus cytokines, the induction of mRNA was greatly reduced. Again, specific patterns of action were revealed: Il-6 had the most potent effect on CYP3A4, whereas TNF-alpha was the most potent with CYP1A genes. In all cases, changes at the protein levels paralleled changes at the mRNA levels. In cells preinduced with beta-naphthoflavone or rifampicin, the decay with time of the levels of the CYP1A2 or CYP3A4 proteins, after the removal of the inducer, was not affected by cytokines. We conclude that cytokines strongly repress the inducibility of CYP1As and CYP3A4 genes at a transcriptional or a posttranscriptional level, but affect neither the rate of translation of CYP mRNAs nor the rate of degradation of the CYP proteins in these cultures.