Nephrotoxicity: A better mechanistic understandings using histochemistry and cytochemistry

Bach, Peter H.

doi:10.1016/s0079-6336(11)80183-x

Cited by 3 publications

(1 citation statement)

References 33 publications

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“…MECHANIShl OF RPN CAUSED BY ANALGESICS AND NSAIDs Data derived from the BEA and other models of RPN together with what is known about the chronically induced lesion in animals and man have been synthesized into what is now regarded as the "textbook explanation" for RPN (9,10,13,16,18). The morphological and histochemical changes (8,15,19,82,85) support distinct pathological changes following a papillotoxic insult.…”

Section: Clironic Degenerative Cliaitgesmentioning

confidence: 99%

Renal Papillary Necrosis—40 Years On

Bach

Thanh

1998

Toxicol Pathol

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Analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) are well recognized as a major class of therapeutic agent that causes renal papillary necrosis (RPN). Over the last decade a broad spectrum of other therapeutic agents and many chemicals have also been rcportcd that have the potential to cause this lesion in animals and man. There is consensus that RPN is the primary lesion that can progress to cortical degeneration; and it is only at this stage that the lesion is easily diagnoscd. In the absence of sensitive and selective noninvasive biomarkers of RPN there is still no clear indication of which compound, under what circumstances, has the greatest potential to cause this lesion in man. Attempts to mimic RPN in rodents using analgesics and NSAIDs have not provided robust models of the lesion. Thus, much of the research has concentrated on those compounds that cause an acute or subacute RPN as the basis by which to study the pathogenesis of the lesion. Based on the mechanistic understanding gleaned from these model compounds it has been possible to transpose an understanding of the underlying processes to the analgesics and NSAIDs. The mechanism of RPN is still controversial. There are data that support microvascular changes and local ischemic injury as the underlying cause. Alternatively, several model papillotoxins, some analgesics, and NSAIDs target selectively for the medullary interstitial cells, which is the earliest reported aberration, after which there are a series of degenerative processes affecting other renal cell types. Many papillotoxins have the potential to undergo prostaglandin hydroperoxidase-mediated metabolic activation, specifically in the renal medullary interstitial cells. These reactive intermediates, in the presence of large quantities of polyunsaturated lipid droplets, result in localized and selective injury of the medullary interstitial cells. These highly differentiated cells do not repair, and it is generally accepted that continuing insult to these cells will result in their progressive erosion. The loss of these cells is thought to be central to the degenerative cascade that affects the cortex. There is still a need to understand better the primary mechanism and the secondary consequences of RPN so that the risk of chemical agents in use and novel molecules can be fully assessed.

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Section: Clironic Degenerative Cliaitgesmentioning

confidence: 99%

Renal Papillary Necrosis—40 Years On

Bach

Thanh

1998

Toxicol Pathol

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Fluorescent Probes for the Assessment of the Subcellular Effects of Chemicals and Disease Processes In Vivo and In Vitro

Bach

Reynolds

Brant

1993

Biotechnology Applications of Microinjection, Microscopic Imaging, and Fluorescence

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Normal Ultrastructure of the Kidney and Lower Urinary Tract

Verlander

1998

Toxicol Pathol

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The mammalian urinary tract includes the kidneys, ureters, urinary bladder, and urethra. The renal parenchyma is composed of the glomeruli and a heterogeneous array of tubule segments that are spccialized in both function and structure and are arranged in a specific spatial distribution. The ultrastructure of the glomeruli and renal tubule epithelia have been well characterized and the relationship between the cellular structure and the function of the various components of the kidney have been the subject of intense study by many investigators. The lower, urinary tract, the ureters, urinary bladder, and urethra, which are histologically similar throughout, are composed of a mucosal layer lined by transitional epithelium, a tunica muscularis, and a tunica serosa or adventitia.The present manuscript reviews the normal ultrastructural morphology of the kidney and the lower urinary tract. The normal ultrastructure is illustrated using transmission electron microscopy of normal rat kidney and urinary bladder preserved by in ~vivo perfusion with glutaraldehyde fixative and processed in epoxy resin.

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Nephrotoxicity: A better mechanistic understandings using histochemistry and cytochemistry

Cited by 3 publications

References 33 publications

Renal Papillary Necrosis—40 Years On

Renal Papillary Necrosis—40 Years On

Fluorescent Probes for the Assessment of the Subcellular Effects of Chemicals and Disease Processes In Vivo and In Vitro

Normal Ultrastructure of the Kidney and Lower Urinary Tract

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