Light‐ and electron‐microscope studies of the rat kidney after administration of inhibitors of the citric acid cycle <i>in vivo</i>: Changes in the proximal convoluted tubule during fluorocitrate poisoning

McDowell, Elizabeth M.

doi:10.1002/path.1711080406

Cited by 18 publications

(5 citation statements)

References 35 publications

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“…The kidneys had mitochondrial swelling with disorganization and disruption of the mitochondrial cristae. The ultrastructural findings in the kidney of the rabbits are similar to those observed in experimental poisoning FA mice (McDowell 1972). The hydropic degeneration observed in the distal convoluted tubules does not occur in all cases of poisoning probably due to the amount of FA contained in the plant ingested, and the time necessary to eliminate this substance in the kidney.…”

Section: Resultssupporting

confidence: 75%

Ultrastructural lesions in the myocardium and kidneys of rabbits in experimental acute Amorimia exotropica poisoning

et al. 2016

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RESUMO.-[Lesões ultra-estruturais no miocárdio e rins de coelhos na intoxicação experimental aguda por Amorimia exotropica.] Amorimia exotropica é uma importante planta associada à morte súbita em bovinos no Sul do Brasil. Visando compreender os mecanismos pelos quais a A. exotropica provoca lesões agudas no coração e rins de animais intoxicados, foi conduzido uma intoxicação experimental em coelhos para determinar a histopatologia e ultraestrutura da lesão miocárdica e renal. Depois de receber 18g/kg de planta seca, seis coelhos morreram subitamente. Na necropsia, o fígado apresentava acentuação do padrão Amorimia exotropica is an important plant associated with sudden death in cattle in Southern Brazil. In order to understand the mechanisms by which A. exotropica causes acute lesions in the heart and kidney of intoxicated animals, an experiment was conducted to determine the histopathology and ultrastructure of myocardial and renal lesions of intoxicated rabbits. After receiving 18g/kg of dried plant, six rabbits died suddenly. At necropsy, the liver was swollen and no other macroscopic lesions were observed. Histologically, centrolobular and midzonal hepatocytes were vacuolated. These vacuoles were strong PAS stained positive, suggesting that they corresponded to glycogen accumulations. In some regions of the ventricular septum and ventricles were found vacuoles of different sizes and the kidneys of two rabbits showed vacuolar degeneration on distal convoluted tubules. Ultrastructurally, the myocardium had cardiomyocytes swelling with separation of myofibrils bundles and rupture and disorganization of the sarcomeres. The mitochondria displayed swelling, disorganization, disruption of the mitochondrial cristae, and electron-dense matrix. Some mitochondria exhibited eccentric projections of their membranes with disruption of both outer and inner membranes. The sarcoplasmic reticulum had no alterations, whereas the T-tubule system was occasionally dilated and ruptured. The kidneys had mitochondrial swelling with disorganization and disruption of the mitochondrial cristae. The vacuoles result from the swelling of the endoplasmatic reticulum and usually were located between two basolateral infoldings and mitochondria, occurring preferentially around the nucleus. The myocytes and T system damages induced by A. exotropica result in acute heart failure and death. Furthermore, this mechanism of cardiotoxicity may be common to all plant containing monofluoroacetate.

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Section: Resultssupporting

confidence: 75%

Ultrastructural lesions in the myocardium and kidneys of rabbits in experimental acute Amorimia exotropica poisoning

et al. 2016

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“…This may be attributed to the role of electromagnetic radiation on the hydration of ions of the exposed water which affect on molecules arrangement around charged ions in the experimental animal cells causing disruption and deformation of animal tissue cells. This concurred with Kholodov (1974), Mc Dwell (1974, Ali (2013), Türker and Yel (2014) and Khater and Ibraheim (2016).…”

Section: Electron Microscopic Studies On the Liver Of Studied Ratssupporting

confidence: 78%

Ecotoxicological Effects of Electromagnetic Radiation on the Wild Rat, Rattus norvegicus norvegicus

Khater

Ghareeb

Ibraheim

2018

Egyptian Academic Journal of Biological Sciences, B. Zoology

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Wild rat, Rattus norvegicus is one of the most important pests in rodents. It is the transmitter of a large number of infectious diseases to domestic animals (Dedovic et al., 2012). The chain of toxicoinfection to farmer's food infected by rat urine and feces and also contaminated forage which poses a risk to animal health (Daniels et al., 2003). Different methods were used for reducing economic damage caused by this rodent species. Magnetic radiation is one of the most potent methods for control rats (Pierre et al., 2007). The effects of electromagnetic radiation in biology have been intensively studied on animals (Zwingelberg et al., 1993). It is not shown any toxic effect against rats at low intensity (Boorman et al., 1997). Acute effect on rats become apparent at the higher radiation strengths (Houpt et al., 2003). Moreover, magnetism sciences have developed and become ARTICLE INFO ABSTRACT Article History

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“…Na–K–ATPase activity in distal renal segments is unaffected by the drug [ 24 ], possibly due to reduced OAT expression there [ 25 ] or greater glycolytic capability of that nephron segment. The closely related malonic acid was recognized as early as 1972 [ 26 ] to cause morphological changes in mitochondria by disrupting the Krebs cycle. There may be a single common pathway of injury that is shared between malate-induced renal Fanconi syndrome and hypoxic–ischaemic AKI [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Fumaric acid ester-induced renal Fanconi syndrome: evidence of mitochondrial toxicity

Wan

Siew

Heptinstall

et al. 2021

Clinical Kidney Journal

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Background Fumaric acid esters (FAEs) are used to treat chronic plaque psoriasis. Fumarate is a crucial component of the Krebs cycle, and mitochondrial function. Proximal tubule cells have high energy demands, and rely on aerobic respiration. Proximal tubular dysfunction can cause the renal Fanconi syndrome and acute kidney injury. We sought to better understand the mechanism for this in the context of FAE therapy. Methods We describe a case series of 10 patients with FAE-associated Fanconi syndrome. Patients were diagnosed and managed at a tertiary renal tubular disorder clinic, with examination of serum and urine biochemistry. 5 patients had a renal biopsy with examination of the specimens by electron microscopy. Results The median age was 36.5 years (IQR 32.25-54.25 years). The median dose of FAE was 720 mg/day (IQR 390-720mg). There was low molecular weight proteinuria: median urinary retinol binding protein (RBP) at presentation was 8385 μg/ml (IQR 2793-14600μg/ml) and RBP/creatinine ratio was 710 (IQR 390-2415). All patients had hyperphosphaturia (median fractional excretion of phosphate 24.2%, IQR 20.8-26.9%, normal range <20%), as well as relative hypophosphataemia, with a median serum phosphate concentration of 0.93 mmol/L (IQR 0.83-0.97 mmol/L). Renal histology showed proximal tubular damage and abnormal mitochondrial morphology. Two patients had a favourable biochemical response to treatment with probenecid. Conclusions We document for the first time that FAE-associated renal Fanconi syndrome is associated with mitochondrial damage visible on electron microscopy. This effect may be ameliorated by antagonism of the organic anion transporter with probenecid.

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Light‐ and electron‐microscope studies of the rat kidney after administration of inhibitors of the citric acid cycle in vivo: Changes in the proximal convoluted tubule during fluorocitrate poisoning

Cited by 18 publications

References 35 publications

Ultrastructural lesions in the myocardium and kidneys of rabbits in experimental acute Amorimia exotropica poisoning

Ultrastructural lesions in the myocardium and kidneys of rabbits in experimental acute Amorimia exotropica poisoning

Ecotoxicological Effects of Electromagnetic Radiation on the Wild Rat, Rattus norvegicus norvegicus

Fumaric acid ester-induced renal Fanconi syndrome: evidence of mitochondrial toxicity

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