Enzyme Histochemical Changes in an Acutely Induced Renal Papillary Necrosis

Gregg, Neill J.; Courtauld, E.; Bach, Peter H.

doi:10.1177/019262339001800106

Cited by 16 publications

(4 citation statements)

References 20 publications

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“…The morphological and histochemical changes (8,15,19,82,85) support distinct pathological changes following a papillotoxic insult. The primary morphological changes occur in the interstitial cells in acute (13,16,82,85), subchronic (92), and chronic (13) papillary necrosis. This is followed by damage to the endothelial cells and loops of Henle, and then collecting duct changes (Fig.…”

Section: Clironic Degenerative Cliaitgesmentioning

confidence: 87%

“…The earliest change in the papilla was marked pyknosis of the renal medullary interstitial cells at a time when other cells were normal or near normal. Other investigations using lower doses of BEA and shorter time intervals (15,16,19,82,85) were unable to show any role for microvasculature injury in the pathogenesis of RPN. The only microvascular effects seen were platelet adhesion well after interstitial necrosis had occurred.…”

Section: Target-selective Injirry To the Renal Mediillary Interstitiamentioning

confidence: 92%

“…Platelet adhesion is not seen before 8 hr after a single dose of BEA. Platelets then increase markedly, but only in those capillaries adjacent to necrosed areas (82). Colloidal carbon outlines microvascular filling and shows how this changes as a result of renal injury.…”

Section: The Pathologic Corrrse Of Bea-induced Rpnmentioning

confidence: 99%

“…1,1998 RENAL PAPILLARY NECROSIS 83 pears to be supported by the arachidonic-acid-dependent metabolism of 2-bromoethanamine to a cytotoxic metabolite in cultured rat medullary interstitial cell cultures (86). These differences also appear to apply iii vivo, as BEA has a direct effect on the medullary interstitial cell as the earliest focal lesion (82,85). It is only subsequently that other fine elements of the medulla such as the loops of Henle, capillaries, and collecting duct cells are affected.…”

Section: Bea Cytotoxicity and Rpnmentioning

confidence: 99%

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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: 87%

Section: Target-selective Injirry To the Renal Mediillary Interstitiamentioning

confidence: 92%

Section: The Pathologic Corrrse Of Bea-induced Rpnmentioning

confidence: 99%

Section: Bea Cytotoxicity and Rpnmentioning

confidence: 99%

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Renal Papillary Necrosis—40 Years On

Bach

Thanh

1998

Toxicol Pathol

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N‐Acetyl‐l‐cysteine abolishes the bromoethylamine‐induced choline incorporation into renal papillary tissue

Thielemann

Rodrigo

Oberhauser

et al. 1995

J. Biochem. Toxicol.

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The role of regenerative processes in the protective effect of N-acetyl-L-cysteine (NAC) against bromoethylamine-induced renal papillary necrosis was assessed in rats given bromoethylamine (BEA)(1.2 mmol/kg), N-acetylcysteine (6 mmol/kg), or N-acetyl-cysteine plus BEA. Renal papillary slices were dissected after 15 hours of treatment, and 14C-choline incorporation into total phospholipid, lysophosphatidylcholine, sphingomyelin, and phosphatidylcholine was measured. Bromoethylamine elicited an increase in the incorporation of 14C-choline into choline-containing phospholipid, an effect that was abolished when N-acetylcysteine was administered prior to bromoethylamine. These studies indicate that the defensive mechanism of N-acetylcysteine against bromoethylamine-induced renal papillary necrosis is not related to regenerative processes and that N-acetylcysteine abolishes the bromoethylamine-induced choline incorporation into papillary phospholipid.

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