Kidneys renal tubule

LLC-PK1 Pig kidney Renal tubule epithelial cell Cadmium Cytotoxicity, apoptosis... 

MDCK Dog kidney Renal tubule epithelial cell Organic mercury compounds Cytotoxicity, transepithelial leakiness... 

The US EPA has subsequently published a comprehensive toxicological review of bromate (US EPA, 2001). Studies with rats based on low-dose linear extrapolation, using the time-to-tumour analysis, and using the Monte Carlo analysis to sum the cancer potency estimates for kidney renal tubule tumoms, mesotheliomas, and thyroid follicular cell tumours, gave an upper-bound cancer potency estimate for bromate ion of 0.70 per mg/kg day. This potency estimate corresponds to a drinking water unit risk of 2 x 10 per pg/L, assuming a daily water consumption of 2 litres/day for a 70-kg adult. Lifetime cancer risks of 10 , 10 , and 10 are associated with bromate concentrations of 5, 0.5, and 0.05 pg/L, respectively. A major source of uncertainty in these estimates is from the interspecies extrapolation of risk from rats to humans. 

AVP plays a central role in water homeostasis of terrestrial mammals, leading to water conservation by the kidney. OT is primarily involved in milk ejection, parturition and in sexual and maternal behaviour. Both hormones are pqDtides secreted by the neurohypophysis, and both act also as neurotransmitters in the central nervous system (CNS). The major hormonal targets for AVP are the renal tubules and vascular myocytes. The hormonal targets for OT are the myoepithelial cells... 

M (increased kidney weight renal tubule dilation, degeneration of renal tubule epithelium albuminous casts focal interstitial nephritis)... 

Amphotericin B-induced ARF occurs in as many as 40% to 65% of patients treated with the conventional desoxycholate formulation.30 Nephrotoxicity is due to renal arterial vasoconstriction and distal renal tubule cell damage. Risk factors include high doses, treatment for at least 7 days, preexisting kidney dysfunction, and concomitant use of other nephrotoxic drugs.31 Three lipid-based formulations of amphotericin B have been developed in an attempt to decrease the incidence of ARF amphotericin B lipid complex, amphotericin colloidal dispersion, and liposomal amphotericin B. The range of... 

The possible mechanism kidney-induced hypertension is discussed in Section 2.4.2, Mechanisms of Toxicity. Lead appears to affect vitamin D metabolism in renal tubule cells, such that circulating levels of the vitamin D hormone, 1,25-dihydroxyvitamin D, are reduced. This effect is discussed later in this section under Other Systemic Effects. 

Tubular component. Approximately 180 1 of filtrate is processed by the kidneys each day. Depending upon the volume of fluid intake, about 99% of this filtrate must be reabsorbed from the renal tubule back into the vascular... 

Schaub TP, Kartenbeck J, Konig J, Spring H, Dorsam J, Staehler G et al. Expression of the MRP2 gene-encoded conjugate export pump in human kidney proximal tubules and in renal cell carcinoma. J Am Soc Nephrol 1999 10(6) 1159—1169. 

The proteinuria and aminoaciduria, and acidosis and glucosuria where they occur, are probably caused by reversible inhibition of some functions of the renal tubule. There would appear to be no structural damage to the kidney. However, 2 children developed nephrolithiasis while being treated with a low-lactose diet (B7, C5), The time course of events, when galactose is withdrawn from and returned to the diet, suggests that some metabolite of galactose accumulates in the cells of the renal tubules and has an inhibitory effect on the reabsorption of a number of substances. 

After peroral intake of nickel sulphate in mice, kidney damage appeared at the corticomedullary junction [296]. There was loss of renal tubular epithelial cells and protein loss, giving numerous hyaline casts in the renal tubules and collecting ducts, especially prominent in the renal papillae. 

Isolated perfused kidney Isolated tubules Renal cells Cell lines Primary cells Kidney slices Isolated organelles... 

Bellemann, P. (1980). Primary monolayer culture of liver parenchymal cells and kidney cortical tubules as a useful new model for biochemical pharmacology and experimental toxicology. Studies in vitro on hepatic membrane transport, induction of liver enzymes, and adaptive changes in renal cortical enzymes. Arch. Toxicol. 44 63-84. 

The excretion of water soluble waste via the kidneys requires filtration followed by selective reabsorption from and secretion into the renal tubules. Regulation of normal blood pH within very strict limits due to proton secretion and bicarbonate reabsorption is a major role of the kidney. 

Assuming the capsular pressures opposing the movement of water out of the blood and into the top of the nephron are constant, the net filtration pressure is due largely to the blood pressure. Any fall in blood pressure can have a dramatic effect on the efficiency of filtration and therefore clearance of waste materials. So important is the pressure within the renal vasculature that the kidney is critical in regulating systemic blood pressure via the renin-angiotensin-aldosterone (RAA) axis, a physiological process which relies on transport mechanisms within the renal tubules. 

Available data on chronic exposure to 1,4-dichlorobenzene in animal studies include a 76-week inhalation study in rats that resulted in increased liver and kidney weights (Riley et al. 1980) a 2-year oral study in mice that resulted in liver effects (NTP 1987), such as hepatocellular degeneration, and cell necrosis and renal effects such as nephropathy and renal tubular degeneration and a 2-year oral study in rats that resulted in a high rate of mortality and renal effects including nephropathy and degeneration of the renal tubules (NTP 1987). No animal studies of chronic dermal contact with 1,4-dichlorobenzene have been located. 

A plethora of methods has been developed to evaluate renal function by dynamic renography and remote analysis of the excretion of renal function markers. The underlying principle is that the kidneys excrete a majority of small hydrophilic molecules and their clearance, secretion, or fixation in the kidney is quantifiable. When a renal marker in plasma is filtered through the glomeruli, the accumulation of the filtrate in the Bowman s capsule. One or more of the following events may occur in the renal tubule once a marker is filtered or is in plasma [171] ... 

The filtered and secreted marker may irreversibly bind to renal tubule, making their quantification in urine of little value. They are primarily used for static imaging of the kidneys and to obtain information about the functional renal mass. Tc-dimercaptosuccinic acid and Tc-glucoheptonate are good examples of such markers [172 -175]. 

In chronic inhalation studies rats and mice were exposed to 0, 75, 250, or 750ppm 6 hours/day, 5 days/week for 104 weeks. Eor male rats exposed at 750 ppm survival was decreased, and the incidence of renal tubule neoplasms and testicular adenomas was increased. The findings from an extended evaluation of the kidneys showed a significant increase in the incidences of renal tubule adenoma and hyperplasia in high-dose males and females. In high-dose mice there were increased incidences of alveolar/bronchiolar neoplasms in males, whereas females had... 

In a 2-year inhalation study, rats and mice were exposed to 0, 67, 292, or 2056ppm 6 hours/day, 5 days per week. The major finding was a time- and dose-related increase in the incidence of kidney lesions in the male rats. These lesions consisted of cortical multifocal tubular basophilia (indicative of areas of cell regeneration), protein casts, and interstitial inflammation. There was epithelial cell shedding, and the casts were found within dilated renal tubules commonly at the corti-comedullary junction. 

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