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Superoxide Anion Production and Expression of gp91phox and p47phox Are Increased in Glomeruli and Proximal Tubules of Cisplatin‐Treated Rats 下载免费PDF全文
Joyce Trujillo Eduardo Molina‐Jijón Omar Noel Medina‐Campos Rafael Rodríguez‐Muñoz José Luis Reyes Diana Barrera José Pedraza‐Chaverri 《Journal of biochemical and molecular toxicology》2015,29(4):149-156
The chemotherapeutic drug cisplatin has some side effects including nephrotoxicity that has been associated with reactive oxygen species production, particularly superoxide anion. The major source of superoxide anion is nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase. However, the specific segment of the nephron in which superoxide anion is produced has not been identified. Rats were sacrificed 72 h after cisplatin injection (7.5 mg/kg), and kidneys were obtained to isolate glomeruli and proximal and distal tubules. Cisplatin induced superoxide anion production in glomeruli and proximal tubules but not in distal tubules. This enhanced superoxide anion production was prevented by diphenylene iodonium, an inhibitor of NADPH oxidase. Consistently, this effect was associated with the increased expression of gp91phox and p47phox, subunits of NADPH oxidase. The enhanced superoxide anion production in glomeruli and proximal tubules, associated with the increased expression of gp91phox and p47phox, is involved in the oxidative stress in cisplatin‐induced nephrotoxicity. 相似文献
23.
Luz-María Torres Liliana Rivera-Espinosa Juan L. Chávez-Pacheco Carlos F. Navas Joel A. Demetrio Radamés Alemón-Medina Francisca Trujillo Martín Pérez Martha M. Zapata Rocío Cárdenas Citlaltepetl Salinas Arnoldo Aquino Rafael Velázquez-Cruz Manuel-de-Jesús Castillejos 《PloS one》2015,10(11)
Ifosfamide blood concentrations are necessary to monitor its therapeutic response, avoiding any adverse effect. We developed and validated an analytical method by UPLC-MS/MS to quantify ifosfamide in dried blood spots (DBS). Blood samples were collected on Whatman 903® filter paper cards. Five 3 mm disks were punched out from each dried blood spot. Acetonitrile and ethyl acetate were used for drug extraction. Chromatographic separation was carried out in an Acquity UPLC equipment with a BEH-C18 column, 2.1 x 100 mm, 1.7 μm (Waters®). The mobile phase consisted in 5 mM ammonium formate and methanol:acetonitrile (40:48:12 v/v/v) at 0.2 mL/min. LC-MS/MS detection was done by ESI+ and multiple reaction mode monitoring, ionic transitions were m/z1+ 260.99 > 91.63 for ifosfamide and 261.00 > 139.90 for cyclophosphamide (internal standard). This method was linear within a 100–10000 ng/mL range and it was accurate, precise and selective. Ifosfamide samples in DBS were stable for up to 52 days at -80°C. The procedure was tested in 14 patients, ages 1 month to 17 years (9 males and 5 females), with embryonic tumours treated with ifosfamide, alone or combined, at a public tertiary referral hospital. Ifosfamide blood levels ranged from 11.1 to 39.7 μmol/L at 12 hours after the last infusion, while 24-hour levels ranged from 0.7–19.7 μmol/L. The median at 12 hours was 19.5 μmol/L (Q25 14.4–Q75 29.0) and 3.8 μmol/L (Q25 1.5–Q75 9.9) at 24 hours, p<0.001. This method is feasible to determine ifosfamide plasma levels in paediatric patients. 相似文献
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Two glutamic acid analogs, (+)-(S)- and (-)-(R)-4-(2,2-diphenyl-1,3,2-oxazaborolidin-5-oxo)propionic acid ((+)-(S)- and (-)-(R)-Trujillon, respectively), were prepared. The stereospecific activity of their pharmacological properties was studied. The median convulsant dose (CD(50)) and median lethal dose (LD(50)) were analyzed in female Swiss Webster mice and their effects in vivo on unitary electrical activity in globus pallidus neurons were elucidated in male Wistar rats. Compounds were characterized by (1)H, (13)C, and (11)B nuclear magnetic resonance. The LD(50) of (+)-(S)-Trujillon was 449.08 mg/kg and it increased spontaneous motor activity, while with (-)-(R)-Trujillon there was no mortality up to 1,000 mg/kg and it decreased spontaneous motor activity. The CD(50) in experiments with (+)-(S)-Trujillon was 199.34 mg/kg. Unitary recording in globus pallidus neurons showed i.v. administration (+)-(S)-Trujillon (50 mg/kg) increased frequency 79.0 +/- 23.0% in relation to basal response. (-)-(R)-Trujillon and (+)-(S)-glutamate (50 mg/kg each) did not provoke changes in spontaneous basal firing. Local infusion of (+)-(S)-Trujillon (1 nMol) increased spontaneous firing in most neurons tested by 269.0 +/- 83.0% in relation to basal values. Intrapallidal infusion of (-)-(R)-Trujillon (1 nMol) and saline solution did not cause statistically significant changes in globus pallidus spiking. Results showed that (+)-(S)-Trujillon crosses the blood-brain barrier and has stereospecific activity. 相似文献
27.
F?Luna M?Cortés M?Flores B?Hernández A?Trujillo R?DomínguezEmail author 《Reproductive biology and endocrinology : RB&E》2003,1(1):61
The effects on spontaneous ovulation associated with the unilateral or bilateral sectioning of the superior ovarian nerves
(SON) were analyzed in guinea pigs at different time intervals of the estrous cycle. Day 1 of the estrous cycle was defined
as the day when the animal presents complete loss of the vaginal membrane (open vagina). Subsequent phases of the cycle were
determined by counting the days after Day 1. All animals were autopsied on the fifth day of the estrous cycle after surgery.
Sectioning the right, left, or both SONs on day 5 (early luteal phase) resulted in a significant increase in the number of
fresh corpora lutea. Ovulation increased significantly when the left SON (L-SON) was sectioned during late follicular phase
(day 1) and medium luteal phase (day 8). When surgery was performed on days 1 or 8, neither sectioning the right SON (R-SON)
nor sectioning the SON bilaterally had an apparent effect on ovulation rates. Similarly, ovulation rates were not affected
when unilateral (right or left) or bilateral sectioning of the SON was performed during late luteal phase two (day 12). Unilateral
or bilateral sectioning of the SON performed during the early luteal phase (day 5) was associated with a significant decrease
in uterine weight. A comparable effect was observed when the L-SON was sectioned during late follicular phase (day 1), or
medium luteal phase (day 8). No effects on uterine weight were observed when unilateral or bilateral sectioning of the SON
was performed during late luteal phase. Our results suggest that in the guinea pig the SON modulates ovulation, and that the
degree of modulation varies along the estrous cycle. The strongest influence of the SONs on ovulation occurs during early
luteal phase, and decrease thereafter, being absent by late luteal phase. In addition, sectioning the left or the right SON
caused different responses by the ovaries of adult guinea pigs. This paper discusses the mechanisms by which ovulation increased
when the SON was surgically cut. 相似文献
28.
Chintamani Sharma R Badran R Singhal V Saxena S Bansal A 《World journal of surgical oncology》2003,1(1):13
Background
Sweat gland adenocarcinoma is a rare malignancy with high metastatic potential seen more commonly in later years of life. Scalp is the most common site of occurrence and it usually spreads to lymph nodes. Liver, lung and bones are the distant sites of metastasis with fatal results. The differentiation between apocrine and eccrine metastatic sweat gland carcinoma is often difficult. The criteria's are inadequate to be of any practical utility. 相似文献29.
Lorda-Sanchez I Garcia-Ruiz PJ Rodriguez de Alba M Montoya J Playan A Sarasa JL Trujillo MJ Sanz R Ramos C Ayuso C 《Genetic counseling (Geneva, Switzerland)》2000,11(3):261-265
A MELAS phenotype and a paternal inherited inversion of chromosome 10 in a female patient: We describe a patient suffering from encephalomyopathy with overlapping symptoms, including MELAS and Kearn-Sayre syndrome features. Mutations in tRNA LEU (UUR) were not found in mtDNA of blood cells, suggesting a different genetic defect. Cytogenetic studies revealed a paternal inherited pericentric inversion of chromosome 10 (p13;q22) pat. Although the presence of the same inversion in the father and in the apparently asymptomatic sister does rather suggest that the concurrence of the mitochondrial disease in the patient was due to chance, some alternative explanations to associate both events might be proposed. 相似文献
30.
The pathogenesis-related accumulation of superoxide radical anions (O·−
2) and hydrogen peroxide (H2O2) was comparatively analyzed in a barley line (Hordeum vulgare L. cv Sultan-5) carrying the powdery mildew (Blumeria graminis f.sp. hordei, Speer, Bgh) resistance gene Mla12, and in susceptible mutants defective in Mla12 or in genes “required for Mla12-specified disease resistance” (Rar1 and Rar2). In-situ localization of reactive oxygen intermediates was performed both by microscopic detection of azide-insensitive
nitroblue tetrazolium (NBT) reduction or diaminobenzidine (DAB) polymerization, and by an NBT-DAB double-staining procedure.
The Mla12-mediated hypersensitive cell death occurred either in attacked epidermal cells or adjacent mesophyll cells of wild-type plants.
Whole-cell H2O2 accumulation was detected in dying cells, while O·−
2 emerged in adjacent cells. Importantly, all susceptible mutants lacked these reactions. An oxalate oxidase, which is known
to generate H2O2 and has been implicated in barley resistance against the powdery mildew fungus, was not differentially expressed between
the wild type and all mutants. The results demonstrate that the Rar1 and Rar2 gene products, which are control elements of R-gene-mediated programmed cell death, also control accumulation of reactive oxygen intermediates but not the pathogenesis-related
expression of oxalate oxidase.
Received: 7 January 2000 / Accepted: 2 June 2000 相似文献