Renal tubular hypertrophy

Other Effects Other effects noted with PFCs in rats include renal tubular hypertrophy and increased kidney weights, decreased red blood cell numbers and hematocrit, and, with FTOHs, ameloblast degeneration with tooth breakage (Ladies et al. 2005, 2008 Cui et al. 2009). The effects on teeth are not apparent in toxicological studies conducted with PFCAs, indicating that these effects may be specific to either the parent compound or one of its non-PFCA metabolites. No effects of PFOA on the incidence of chronic kidney disease were noted in the Washington Works cohort (C8 Science Panel 2012e). 

Inhalation exposure of mice at 7000ppm 6hrs/day, 5 days week for 14 weeks caused hyperreactivity and diminished response to an auditory alerting stimulus during exposures and significantly increased liver weights at the end of exposures rats similarly exposed also had a significantly increased incidence of hepatic centrilobular hypertrophy. Repeated intraperitoneal administration of 1.5g/kg caused evidence of renal tubular injury in rats effects were attributed to cyclohexanol, the main metabolite of cyclohexane."... 

Forestomach and the renal proximal tubule are the primary target tissues of chlorothalonil toxicity in Sprague-Dawley rats. Toxicity is characterized by hypertrophy, hyperplasia, vacuolization, and degeneration of renal tubular epithelium and acanthosis, hyperkeratosis, and hyperplasia of the squamous epithelium of the forestomach. Chlorothalonil is a well-known skin and eye irritant. Sustained contact with the squamous epithelium of the forestomach can lead to an inflammatory response. The earliest observation following chlorothalonil administration at 175 mgkg day to rats for varying periods of time for up to 91 days has been characterized by multifocal ulceration and rosion of the mucosa,... 

LOEL 250 mg/kg/day (mice) 125 mg/kg/day [10, 11] (rats) hepatocellular hypertrophy NOEL 10 mg/kg/day increases in liver and [1] kidney weights, increases in the incidence of hepatocellular hypertrophy, increases in thyroidparathyroid weights, hypertrophy and hyperplasia of the thyroid high incidences of trace-to-mild chronic nephritis in kidneys of male rats and increased pigmentation of the renal tubules in female rats LOAEL = 312 mg/kg/day (rats) 125 mg/kg/day [10, 11] (mice) hepatocellular neoplasms and adenomas or adenocarcinomas of the liver mononuclear cell leukemia adenomas or hyperplasia of the renal tubular cells in exposed male rats follicular cell adenomas or carcinomas of the thyroid in exposed female rats and female mice alveolar/bronchiolar adenomas or carcinomas in male mice 52 mg/kg Paroil intestinal activities of aryl [13] hydrocarbon hydroxylase (increase), UDP-glucuronosyltransferase (decrease) and epoxide hydrolase (increased)... 

Angiotensin-II AT, Human cDNA Artherosderosis, cardiac hypertrophy, congestive heart failure, hypertension, myocardial infarction, renal disease, cancer, diabetes, obesity, glaucoma, cystic fibrosis, Alzheimer s disease, Parkinson s disease Smooth muscle contraction, cell proliferation and migration, aldosterone and ADH release, central and peripheral sympathetic stimulation, extracellular matrix formation, tubular sodium retention, neuroprotection... 

However, resistance to loop diuretics can occur by various mechanisms (36). These include poor adherence to therapy, poor absorption, progressive worsening of heart failure, excess volume loss, renal insufficiency, secondary hyperaldosteronism, and hypertrophy of the tubular cells of the distal nephron. Resistance due to inadequate drug absorption—either its speed or extent—is common with furosemide, which is poorly absorbed (34). Once recognized, this hurdle to response can be overcome by using loop diuretics that are predictably well absorbed, such as bumetanide and torasemide or by giving intravenous furosemide (37). 

Andoh et al developed an experimental model of TAC-induced chronic nephrotoxicity using salt-depletion in rats [687, 704]. A particular characteristic of this model is that renal functional changes and structural injury occur with TAC blood levels equivalent to those found in treated patients, in a striking contrast with the CSA chronic nephrotoxicity model, where extremely high CSA blood levels are necessary to produce injury. In this TAC model, there is an early and dose-dependent decrease in GFR and RBF with a parallel RVR increase followed by a late development of renal interstitial fibrosis involving the itmer strip and medullary rays, arteriolar hyahnosis, tubular atrophy and hypertrophy and medullary thick ascending limb size variance. Structural injury showed a significant positive correlation with decreased renal function [687, 704,705]. 

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