Alamine aminopeptidase excretion after mercuric chloride renal failure
Abstract
Within the first 24 hr after induction of acute renal failure in rats by 4.7 mg/kg body weight of mercuric chloride, there was a highly significant (P < 0.001) increase in urine AAP activity. Enzymuria sharply declined during the next 48 hr, although did not return to baseline until Day 4. A transient secondary period of hyperenzymuria occurred 8 to 10 days after injection. In addition to the type of renal injury, timing of sample collections influences the diagnostic value of urine enzyme determinations.
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Cited by (10)
Mechanisms Involved in the Renal Handling and Toxicity of Mercury
2018, Comprehensive Toxicology: Third EditionOne of the most important factors that determines the dispositional and toxicological fate of environmentally relevant forms of mercury in the body is the strong bonding affinity that exists between mercuric ions and reduced sulfur atoms of certain biomolecules. The formation of unique chemical species by the bonding of inorganic and organic mercuric ions in both extracellular and intracellular compartments of the body turns out to be a crucial part of the mechanisms involved in the handling and toxicity of inorganic and organic mercury in specific target tissues and organs, especially in the liver and kidneys. For example, certain membrane transporters present in renal proximal tubular epithelial cells have been shown to import certain species of mercury formed in extracellularly, while other transporters have been shown to export mercuric species formed in intracellular compartments of these target cells. Interestingly, the specific thiol S-conjugates that gain entry into the intracellular milieu of a target (renal) epithelial cell may not be the same type of thiol S-conjugate that is exported out of the cell. Over the last couple of decades, significant progress has been made in identifying membrane transporters in renal proximal tubular cells that take up and export certain thiol S-conjugates mercury. This chapter not only reviews the advances in understanding the roles of the transporters taking up and exporting endogenously formed species of mercury by renal tubular epithelial cells, but it also reviews some of the more relevant findings pertaining to key intracellular biochemical effects of mercuric ions that likely play a role in intoxicating proximal tubular cells. Moreover, discussion of factors that modify the proximal tubular uptake and subsequent toxicity of mercuric species has also been included.
Renal Handling and Toxicity of Mercury
2010, Comprehensive Toxicology, Second EditionMercury is a unique heavy metal that can exist in the environment in several physical and chemical forms, including elemental mercury, which is a liquid at room temperature. All forms of mercury express some form of toxic effects in target organs, especially in the kidneys. Interestingly, the epithelial cells lining the straight portions of renal proximal tubules are among the most vulnerable to the toxic effects of mercury. The biological and toxicological activity of mercurous and mercuric ions can be defined largely by chemical bonding with critical nucleophilic sites in and around target cells. Due to the high bonding affinity between mercuric ions and sulfur-reduced atoms, particular interest is paid to the interactions that occur between mercuric ions and thiol group(s) of proteins, peptides, and amino acids. Chemical interactions between mercuric ions and sulfhydryl groups in molecules of albumin, metallothionein, glutathione, and cysteine have been implicated in the mechanisms participating in the uptake, accumulation, transport, and toxicity of mercuric ions in the renal proximal tubule. Numerous factors, both within and outside the intracellular compartment of proximal tubular epithelial cells, influence greatly the susceptibility of these target cells to the injurious effects of mercury. These very factors serve as the theoretical basis for most of the currently employed therapeutic strategies used for mercury poisoning in humans. This chapter provides a brief update on the current body of knowledge regarding the mechanisms involved in the renal cellular uptake, accumulation, elimination, and toxicity of mercury.
Urinary enzymes, nephrotoxicity and renal disease
1982, ToxicologyThe value of urinary enzymes as non-invasive tests of renal integrity in toxicology and medicine is reviewed. Urinary enzymes provide very sensitive indicators of renal damage and although a wide variety of enzymes have been assayed, only a few have proved useful because of practical considerations. The assay of NAG and AAP have proved to be most valuable, while other enzymes, including LDH, lysozyme, kallikrein, carbonic anhydrase C, arylsulphatase A, alkaline phosphatase and γGT have proved to be useful in particular situations. The diagnostic potential of urinary enzymes is often enhanced by the simultaneous assay of more than one enzyme, particularly if the activities of the enzymes used are high in different regions of the nephron. Isoenzyme studies provide additional diagnostic information. Urinary enzyme assays are most useful when carried out in conjunction with simple non-invasive test of renal function, e.g. osmolality, and protein selectivity.
The marked susceptibility of the kidney to toxic damage and the effect of drugs on subcellular organelles are discussed. Further, the problems of assaying enzymes in urine are considered and the various ways in which they can be overcome is described. Recent improvements in techniques, including automation, miniphotometers and “dipstick” tests, are described. The importance of age is emphasised, and different ways of expressing enzyme activities, which allow for varying urine flow, is discussed.
Urinary enzymes can play a role in the detection of nephrotoxicity, monitoring the level of safe doses in patients, the evaluation of new drugs and in the control of industrial workers using hazardous chemicals. The most important nephrotoxins are certain antibiotics, heavy metals, herbicides and anti-inflammatory drugs. Urinary enzymes have considerable potential value for the early warning of rejection in transplant patients, screening for renal disease and for the detection of renal damage secondary to hypertension, diabetes and rheumatoid arthritis. The review concludes by considering how urinary enzymes will be used in the future as an aid to the toxicologist and clinician.
Proximal tubule brush border alterations during the course of chromate nephropathy
1981, Toxicology and Applied PharmacologyTubular transport abnormalities reportedly predominate over alterations in glomerular filtration rate and epithelial morphology during the early phase of Na-chromate-induced acute renal failure. We have studied the role of the brush border membrane in the sequence of events after the subcutaneous injection of Na2CrO4 (20 mg/kg body weight) to rats. Brush border integrity was evaluated by ultrastructural criteria and the activities of several enzymes assayed in vitro on purified brush border membrane preparations. By electron microscopy, subtle alterations of microvillar morphology were present within 1 hr of chromate injection. Alkaline phosphatase activity declined significantly by 2 hr but represented the only brush border enzyme alteration at this earliest time of study. During 0–2 hr, Cin declined to 0.90 ± 0.04 ml/min from a control value of 1.30 ± 0.04 then increased during the 2–4 hr period to 1.09 ± 0.05 ml/min. The fractional excretion of lysozyme at 0–2 and 2–4 hr and of phosphate at 2–4 hr, and the urine excretion of N-acetyl-glucosaminidase at 0–2 and 2–4 hr increased significantly in chromate rats and exceeded values in saline-injected rats for the corresponding collection periods. [14C]Leucine incorporation into proteins of renal cortex and brush border was 50% or less of control at 2 hr after chromate. By 12–16 hr, brush border enzyme abnormalities were well established and became more severe with longer periods of observation coincident with advancing degrees of renal insufficiency. These results indicate that chromate-induced epithelial cell toxicity and tubular transport defects become operative within the first 2–4 hr after injection of Nachromate. Whereas injury to the brush border membrane is a feature of chromate nephropathy, the available evidence does not strongly favor the view that transport defects are attributable to microvillar pathology.
Mechanisms Involved in the Renal Handling and Toxicity of Mercury
2018, Comprehensive Toxicology, Third Edition: Volume 1-15Molecular interactions with mercury in the kidney
2000, Pharmacological Reviews