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Nguyen T. K. Thanh - One of the best experts on this subject based on the ideXlab platform.
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phospholipiduria in 2 bromoethanamine induced Renal Papillary Necrosis
Biomarkers, 2001Co-Authors: Nguyen T. K. Thanh, David K Obatomi, P. H. BachAbstract:The possibility that phospholipid excretion in urine might be a marker of Renal Papillary Necrosis (RPN) induced by 2-bromoethanamine (BEA) was investigated in male Wistar rats following a single i.p. injection in time course and dose-response experiments. Urinary and serum creatinine as well as electrolytes were also measured in parallel to histological examination of tissues. A single i.p. injection of BEA caused a characteristic dose-related change in urinary phospholipids, notably sphingomyelin (SPM), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) excretion on the first day of treatment. At a lower dose of 30 mg kg -1 BEA, there was no alteration in the levels of the phospholipids; however, significant increases in the excretion of SPM, PC and PE at the 90 and 240 mg kg -1 dose level were observed. There was an early increase in the three phospholipids irrespective of whether the excretion is expressed in units per hour excretion or units per milligram creatinine. The increased excretion of SPM and PC remained over 4 days while PE levels returned to normal after day 1. On day 1, urinary flow rate and creatinine were also increased significantly while there was a significant fall in the levels of some electrolytes (Na + , K + , Cl - ). Parallel histological examination also confirmed the presence of RPN at the two higher doses (90, 240 mg kg -1 ) of BEA. Other measurements such as blood urea nitrogen and the levels of Ca 2+ and Mg 2+ in blood were unaffected at all dose levels of BEA. These results demonstrate the potential of specific urinary phospholipids as diagnostic bio-markers for early Renal injury associated with RPN and may provide an important improvement in the non-invasive approach to the therapeutic management of Renal diseases, and potentially prevent further degenerative changes.
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Renal Papillary Necrosis--40 years on.
Toxicologic pathology, 1998Co-Authors: Peter H Bach, Nguyen T. K. ThanhAbstract: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 reported 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 diagnosed. 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 gleane...
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Renal Papillary Necrosis 40 years on
Toxicologic Pathology, 1998Co-Authors: Peter H Bach, Nguyen T. K. ThanhAbstract: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 reported 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 diagnosed. 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.
Peter H Bach - One of the best experts on this subject based on the ideXlab platform.
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Renal Papillary Necrosis--40 years on.
Toxicologic pathology, 1998Co-Authors: Peter H Bach, Nguyen T. K. ThanhAbstract: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 reported 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 diagnosed. 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 gleane...
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Renal Papillary Necrosis 40 years on
Toxicologic Pathology, 1998Co-Authors: Peter H Bach, Nguyen T. K. ThanhAbstract: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 reported 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 diagnosed. 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.
William W. Carlton - One of the best experts on this subject based on the ideXlab platform.
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Diphenylamine-induced Renal Papillary Necrosis and Necrosis of the Pars Recta in Laboratory Rodents
2016Co-Authors: S.d. Lenz, William W. CarltonAbstract:Abstract. The nephrotoxicity of diphenylamine, the parent compound of the mefenamate family of non-steroidal anti-inflammatory drugs, was evaluated in male Syrian hamsters, male Sprague-Dawley rats, and male Mongolian gerbils. Total Renal Papillary Necrosis was observed in four of ten, seven of ten, and six of ten male Syrian hamsters orally treated with diphenylamine at respective doses of 400 mg/kg body weight/day, 600 mg/ kg body weight/day, and 800 mg/kg body weight/day. Total Renal Papillary Necrosis was also observed in five of ten and four of ten male Syrian hamsters intraperitoneally treated with diphenylamine at respective doses of 600 mg/kg body weight/day and 800 mg/kg body weight/day. Focal intermediate Renal Papillary Necrosis was induced in two hamsters orally given diphenylamine at 600 mg/kg body weight/day and in two of ten hamsters intraperitoneally given diphenylamine at 800 mg/kg body weight/day. Apex-limited Necrosis of the medullary interstitial cells and vasa recta and degeneration of the Renal interstitial matrix occurred in two Sprague-Dawley rats orally administered diphenylamine at 800 mg/kg body weight/day. Degeneration and Necrosis of the pars recta was induced in seven of ten hamsters intraperitoneally given diphenylamine at 400 mg/kg body weight/ day. Gross and microscopic Renal lesions were not observed in any Mongolian gerbils. It was concluded that the Syrian hamster is more susceptible to the papillotoxic effects of diphenylamine than the Sprague-Dawley rat and the Mongolian gerbil. Renal Papillary Necrosis in the Syrian hamster treated orally with diphenylamin
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Experimental Renal Papillary Necrosis in the Mongolian Gerbil (Merianes unguiculatus)*
2016Co-Authors: D C Wolf, William W. Carlton, J. TurekAbstract:Sequential light microscopic and ultrastructural examination of kidneys from male and light microscopic examination of female Mongolian gerbils given 250 mg 2-bromoethylamine hydrobromide (BEA)/kg body weight ip were performed. In addition, male Mongolian gerbils were treated with both BEA and ip injections of either water, dimethyl sulfoxide, piperonyl butoxide, or reserpine. Light microscopic Renal lesions in male Mongolian gerbils progressed from congestion of the vasa recta of the proximal inner medulla at 6 hr post-treatment to total Renal Papillary Necrosis (RPN) at 24 hr post-treatment. There was no sex difference in sensitivity to BEA. Ultrastructural alterations in male gerbils were restricted to the vasa recta. Vascular lesions of endothelial swelling and pericapillary edema in the vasa recta of the proximal inner medulla was observed 2 hr post-treatment and progressed to occlusion by platelets adherent to exposed basement mem-branes at 6 hr post-treatment. Diuresis induced by injections of saline and injections of dimethyl sulfoxide or piperonyl butoxide did not affect the development of BEA-induced RPN. Reserpine slowed the devel-opment of BEA-induced RPN by its vasodilatory effect on the Renal vasculature, not by blocking the en-dothelial toxicity of BEA. RPN induced by BEA in the Mongolian gerbil is apparently an ischemic Necrosis of the inner medulla that develops secondary to endothelial damage of the vasa recta
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Early ultrastructural lesions of diphenylamine-induced Renal Papillary Necrosis in Syrian hamsters
Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie, 1995Co-Authors: S.d. Lenz, John J. Turek, William W. CarltonAbstract:The ultrastructural lesions of diphenylamine-induced Renal Papillary Necrosis in Syrian hamsters were characterized by transmission electron microscopy. Twenty-four male Syrian hamsters were orally administered 600 mg diphenylamine/kg body weight as a single dose. At 30 minutes and at 1, 2, 4, 8, 16 and 24 hours after administration of diphenylamine, three hamsters were anesthetized with pentobarbital, perfused via the left ventricle with half-strength KARNOVSKY's fixative, and the Renal papilla and outer medulla collected. Three hamsters administered 0.5 ml peanut oil/kg body weight (vehicle controls) were anesthetized at 24 hours, perfused, and the Renal papilla and outer medulla collected. Initial ultrastructural lesions were observed in the endothelial cells of the ascending vasa recta in the proximal portion of the Renal papilla at 1 hour after diphenylamine administration. The endothelial cell basal plasma membrane was elevated from the basal lamina, forming large subendothelial vacuoles. Alterations in inner medullary interstitial cells, endothelial cells of the descending vasa recta, and the epithelial cells of the thin limbs of Henle and the medullary collecting tubules were observed subsequent to the lesion in the ascending vasa recta. It was concluded that the endothelial cell of the ascending vasa recta is the target cell in diphenylamine-induced Renal Papillary Necrosis in Syrian hamsters.
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Decreased incidence of diphenylamine-induced Renal Papillary Necrosis in Syrian hamsters given dimethylsulphoxide.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 1991Co-Authors: S.d. Lenz, William W. CarltonAbstract:Abstract The Renal papillotoxicity of diphenylamine dissolved in dimethylsulphoxide (DMSO) was investigated in male Syrian hamsters, male Sprague-Dawley rats and female Mongolian gerbils. When diphenylamine in DMSO was administered orally to male Syrian hamsters (400, 600 or 800 mg/kg body weight/day for up to 9 days), the incidence of Renal Papillary Necrosis was almost zero. Hamsters pretreated with DMSO (0.5 ml/100 g body weight/day) and 1 hr later given 400, 600 or 800 mg diphenylamine in peanut oil/kg body weight/day for 3 consecutive days had significantly reduced incidences of Renal Papillary Necrosis ( 0 10 , 0 10 and 1 10 in the low-, mid- and high-dose groups, respectively) when compared with hamsters given similar doses of diphenylamine but not pretreated with DMSO ( 5 10 , 7 10 and 5 10 in the lo was observed in two Sprague-Dawley rats given 800 mg diphenylamine in DMSO/kg body weight/day orally for 9 days. Focal, intermediate Renal Papillary Necrosis was observed in two additional rats administered 800 mg diphenylamine in DMSO/kg/day orally for 9 days. Renal Papillary Necrosis was not observed in any of the Mongolian gerbils. The results of these studies suggest that DMSO protects against diphenylamine-induced Renal Papillary Necrosis in male Syrian hamsters.
John J. Turek - One of the best experts on this subject based on the ideXlab platform.
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Early ultrastructural lesions of diphenylamine-induced Renal Papillary Necrosis in Syrian hamsters
Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie, 1995Co-Authors: S.d. Lenz, John J. Turek, William W. CarltonAbstract:The ultrastructural lesions of diphenylamine-induced Renal Papillary Necrosis in Syrian hamsters were characterized by transmission electron microscopy. Twenty-four male Syrian hamsters were orally administered 600 mg diphenylamine/kg body weight as a single dose. At 30 minutes and at 1, 2, 4, 8, 16 and 24 hours after administration of diphenylamine, three hamsters were anesthetized with pentobarbital, perfused via the left ventricle with half-strength KARNOVSKY's fixative, and the Renal papilla and outer medulla collected. Three hamsters administered 0.5 ml peanut oil/kg body weight (vehicle controls) were anesthetized at 24 hours, perfused, and the Renal papilla and outer medulla collected. Initial ultrastructural lesions were observed in the endothelial cells of the ascending vasa recta in the proximal portion of the Renal papilla at 1 hour after diphenylamine administration. The endothelial cell basal plasma membrane was elevated from the basal lamina, forming large subendothelial vacuoles. Alterations in inner medullary interstitial cells, endothelial cells of the descending vasa recta, and the epithelial cells of the thin limbs of Henle and the medullary collecting tubules were observed subsequent to the lesion in the ascending vasa recta. It was concluded that the endothelial cell of the ascending vasa recta is the target cell in diphenylamine-induced Renal Papillary Necrosis in Syrian hamsters.
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experimental Renal Papillary Necrosis in the mongolian gerbil meriones unguiculatus
Toxicologic Pathology, 1992Co-Authors: D C Wolf, W W Carlton, John J. TurekAbstract:Sequential light microscopic and ultrastructural examination of kidneys from male and light microscopic examination of female Mongolian gerbils given 250 mg 2-bromoethylamine hydrobromide (BEA)/kg body weight ip were performed. In addition, male Mongolian gerbils were treated with both BEA and ip injections of either water, dimethyl sulfoxide, piperonyl butoxide, or reserpine. Light microscopic Renal lesions in male Mongolian gerbils progressed from congestion of the vasa recta of the proximal inner medulla at 6 hr post-treatment to total Renal Papillary Necrosis (RPN) at 24 hr post-treatment. There was no sex difference in sensitivity to BEA. Ultrastructural alterations in male gerbils were restricted to the vasa recta. Vascular lesions of endothelial swelling and pericapillary edema in the vasa recta of the proximal inner medulla was observed 2 hr post-treatment and progressed to occlusion by platelets adherent to exposed basement membranes at 6 hr post-treatment. Diuresis induced by injections of saline and injections of dimethyl sulfoxide or piperonyl butoxide did not affect the development of BEA-induced RPN. Reserpine slowed the development of BEA-induced RPN by its vasodilatory effect on the Renal vasculature, not by blocking the endothelial toxicity of BEA. RPN induced by BEA in the Mongolian gerbil is apparently an ischemic Necrosis of the inner medulla that develops secondary to endothelial damage of the vasa recta.
James W. Lohr - One of the best experts on this subject based on the ideXlab platform.
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Renal Papillary Necrosis in a patient with sickle cell trait.
Journal of the American Society of Nephrology : JASN, 1997Co-Authors: G Zadeii, James W. LohrAbstract:A patient with sickle cell trait who presented with gross hematuria and was subsequently found to have Renal Papillary Necrosis is presented. The hematuria resolved with conservative therapy consisting of bed rest and hydration with hypotonic intravenous fluids. The pathophysiology of Renal abnormalities associated with sickle cell trait is described. The management of the primary clinical manifestations of this disorder, hematuria and Papillary Necrosis, are discussed.