Alpha-tocopherol protects against the renal damage caused by potassium dichromate.

Exposure to hexavalent chromium (Cr(6+)) causes mutagenic, carcinogenic, and toxic effects, some of which have been associated with its oxidative capacity. In the kidney, Cr(6+) has been claimed to provoke necrosis of the proximal tubular cells. Our aim was to assess the functional involvement of the different segments that form the nephron in a model of acute renal failure caused by potassium dichromate and the participation of oxidative damage in this process. We also studied the possible protective effect of alpha-tocopherol (alpha-TOC) against renal damage. Wistar female rats 200g body weight (bw) received potassium dichromate (15mg/kg, sc, single dose). Lipid peroxidation and renal function were evaluated on days 0, 1, 2, 3, 7, 10, and 14. A second group received alpha-TOC (125mg/kg, by gavage) 5 days before and during dichromate exposure (same dose as for the first group), and was monitored at 0, 2, and 7 days of exposure. Creatinine clearance, glucose and sodium fractional excretions, p-aminohippurate uptake, free-water and osmolal clearances were also measured. Thiobarbituric acid-reactive substances were quantified in renal cortex. The results revealed altered proximal tubule function, decreased glomerular filtration, and distal segment dysfunction, accompanied by oxidative damage 48h after exposure to dichromate. In the alpha-TOC-treated group proximal reabsorptive and secretory functions were preserved, suggesting that oxidative damage is a participating mechanism in dichromate toxicity on these functions. In contrast alpha-TOC did not prevent glomerular or distal dysfunction, indicating selectivity of the protection afforded by this compound on the toxicity of dichromate, at the several components of the nephron.

A high-throughput colorimetric and fluorometric microassay for the evaluation of nitroimidazole derivatives anti-trichomonas activity.

Several nitroimidazole derivatives were synthesized and tested as possible trichomonicidal agents. A fast, simple, practical and reliable in vitro colorimetric method was applied to the screening of the nitroimidazole derivatives anti-trichomonas activity. The colorimetric technique was based on the use of Alamar blue as a redox-indicator. The test was carried out both qualitatively (minimal inhibitory concentration determined by naked eye observation) and quantitatively (fluorometric determination of 50% and 90% inhibitory concentrations), the latter took advantage of the dye fluorometric properties. The performance of the method was excellent affording an exactitude 97.86% and a reproducibility of 95% and no interference of the trichomonas-culture medium was observed during the test. Some of the nitroimidazole compounds tested showed a fair trichomonicidal activity, however none of them was as active as the model compound, metronidazole.

Indomethacin decreases furosemide-induced natriuresis and diuresis on the neonatal kidney.

Indomethacin is used to pharmacologically occlude patent ductus arteriosus in preterm infants. It induces renal untoward effects and furosemide is administered simultaneously to counteract them. The effect of furosemide is blunted by indomethacin. We analyzed comparatively the interactions of furosemide and indomethacin at the organic anion transport system in adult and newborn individuals. Adult and 5-day-old Wistar rats were allocated into three groups: (1) indomethacin (10 mg/kg, ip); (2) furosemide (2 mg/kg, ip); and (3) indomethacin/furosemide, at the same doses. Urinary flow, glomerular filtration rate (GFR), sodium and potassium fractional excretions, and free-water and osmolal clearances were estimated. Para-aminohippuric acid (PAH) uptake was measured in renal cortical slices to study the organic anion's secretory pathway. In adult and newborn rats, furosemide-induced increments in urinary fluxes and excretions of sodium and potassium were blunted by indomethacin administered simultaneously. PAH uptake was decreased to a further extent by indomethacin than by furosemide, suggesting that inhibition of the diuretic effect might be related to competition in the secretion of furosemide. Inhibitory interaction between indomethacin and furosemide was achieved at approximately 10-fold lower concentrations in the newborn than in the adult rats, suggesting that tubular secretion in the neonate is more sensitive to the action of these drugs than in the adult individual.

Parathyroid hormone increases cytosolic calcium in neonatal nephron through protein kinase C pathway.

In mammals, neonatal positive calcium balance is required for adequate growth. Parathyroid hormone (PTH) plays a central role in this process mainly through its action on the distal nephron. We studied the effect of PTH on cytosolic calcium in distal segments from neonatal rat kidney. PTH elicited a concentration-dependent increase in cytosolic calcium in neonatal distal nephron (EC(50)=0.5 nM) but not in proximal tubules. At similar PTH concentrations the response was higher in the neonatal than in the adult tubules. The response was associated with protein kinase C (PKC), since phorbol myristate acetate (100 nM) increased [Ca(2+)]i, and staurosporin, an inhibitor of PKC, decreased (10 nM) or suppressed (100 nM) the PTH effect. cAMP analogues did not change [Ca(2+)]i. The response was diminished in low external calcium (0.1 mM) and absent at zero calcium, indicating dependency on external calcium. Resting calcium decreased from 80+/-10.8 to 28.6+/-2.6 nM at zero [Ca(2+)]e. PTH and nifedipine increased cytosolic calcium in an additive fashion. We show for the first time that PTH increased cytosolic calcium in the distal nephron of neonatal kidney, in a concentration-dependent pattern and in association with PKC activation. Higher sensitivity of the neonatal tubule might facilitate absorption of this cation during the neonatal period, when growth requires a positive balance of calcium.