Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034186 (pyelonephritis)
 6,144 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The carcinogenic effects of aniline and norharman given alone or in combination were examined in rats. Neoplastic changes including hyperplastic changes of the urinary bladder were not found in all groups. Papillomas of forestomach were observed in 5 rats out of 110 rats. However, this was not significantly different among the groups. Pyelonephritis or chronic nephritis were also seen in all groups. Hematological and blood biochemical analysis did not show any notable difference in the animals treated with aniline and/or norharman.
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PMID:Chronic effects of norharman in rats treated with aniline. 741 22

Phenylbutazone is a nonsteroidal anti-inflammatory drug. NTP Toxicology and Carcinogenesis studies were conducted by administering phenylbutazone (greater than 99% pure) in corn oil by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 19 days, 13 weeks, or 2 years. Genetic toxicology studies were performed with Salmonella typhimurium, mouse L5178Y lymphoma cells, and Chinese hamster ovary (CHO) cells. Nineteen-Day Studies: The deaths of 3/5 male and 4/5 female rats that received 600 mg/kg and of 2/5 females that received 300 mg/kg were considered to be chemically related. The final mean body weight of rats that received 300 or 600 mg/kg was 14%-15% or 46% lower than that of vehicle controls. No compound-related deaths occurred in mice (doses up to 600 mg/kg). The final mean body weights of dosed and vehicle control mice were similar. Thirteen-Week Studies: Most rats that received 300 mg/kg and 1/10 male and 2/10 female rats that received 200 mg/kg died early. The final mean body weight of male rats at 300 mg/kg was 31% lower than that of the vehicle controls. The liver weight to body weight ratios were increased in the 200 and 300 mg/kg group of rats. Compound-related lesions occurred mainly in the kidney and included papillary necrosis, papillary edema, and multifocal mineralization. Five of 10 male mice and 4/10 female mice that received 600 mg/kg died early. No other compound-related deaths occurred in mice. Final mean body weights of dosed and vehicle control mice were comparable. The liver weight to body weight ratios were increased for mice at 300 and 600 mg/kg. No compound-related histopathologic effects were observed in mice. Body Weight and Survival in the Two-Year Studies: Two-year studies were conducted by administering 0, 50, or 100 mg/kg phenylbutazone in corn oil by gavage to groups of 50 rats of each sex, 5 days per week for 103 weeks. The doses given groups of 50 mice of each sex on the same schedule were 0, 150, or 300 mg/kg. Mean body weights of high dose rats were generally 6%-11% lower than those of vehicle controls. Mean body weights of mice were similar among all groups except for high dose female mice, which weighed 4%-11% less than vehicle controls. The survival of all groups was similar except for that of the low dose group of male rats, which was significantly lower than that of the vehicle controls at the end of the studies; the survival of the top dose group of female rats and the vehicle control group of female mice was low but not statistically reduced(final survival--male rats: vehicle control, 33/50; low dose, 20/50; high dose, 27/50; female rats: 31/50; 35/50; 22/50; male mice: 36/50; 40/50; female mice: 22/50; 29/50; 32/50). Nonneoplastic and Neoplastic Effects in the Two-Year Studies: Mild pyelonephritis, renal papillary necrosis, and mineralization of the renal papillae in dosed male and female rats and hyperplasia of the renal pelvis epithelium, dilatation of the renal pelvis, and renal cysts in dosed female rats were observed at increased incidences compared with those in vehicle controls. A renal tubular cell carcinoma was observed in one low dose male rat, and renal tubular adenomas were observed in three high dose male rats. A carcinoma of uncertain histogenesis was observed in one low dose female rat. Carcinomas of the renal transitional epithelium were seen in two high dose female rats. When the kidneys were step-sectioned, additional tubular cell adenomas were diagnosed in four low dose and one high dose male rats and in three low dose and one high dose female rats; none was observed in vehicle controls. Papillomas of the transitional epithelium of the urinary bladder were seen in 2/43 low dose male and 1/49 low dose female F344/N rats. The historical incidence of urinary bladder transitional cell neoplasms in male corn oil vehicle control F344/N rats is 5/2,034 (0.2%; highest observed incidence, 2/50) and 4/2,026 (0.2%; highest observed incidence, 1/45) in females. Adrenal medullary hyperplasia was observed at an increased incidence in high dose female rats (veherplasia was observed at an increased incidence in high dose female rats (vehicle control, 3/50; low dose, 6/50; high dose, 19/50). Ulcers of the forestomach were observed at increased incidences in high dose rats (male: 0/50; 5/50; 6/50; female: 2/49; 1/49; 12/49). In high dose female rats, acanthosis (4/49; 0/49; 12/49), hyperkeratosis (3/49; 0/49; 12/49), and basal cell hyperplasia (4/49; 1/49; 12/49) of the forestomach were observed at increased incidences. No neoplasms were associated with these stomach lesions. Peliosis hepatis, centrilobular cytomegaly and karyomegaly, fatty change, hepatocellular degeneration, and coagulative necrosis of the liver were observed in dosed male mice; clear cell foci were observed in five high dose male mice. The incidences of hepatocellular adenomas and adenomas or carcinomas (combined) in male mice were increased in the high dose group (adenomas or carcinomas, combined: 16/50; 14/50; 31/50). Genetic Toxicology: Phenylbutazone was not mutagenic in S. typhimurium strains TA98, TA100, TA1535, or TA1537 when tested with or without exogenous metabolic activation. Phenylbutazone produced a positive response in the mouse lymphoma assay in both the presence and absence of activation. Phenylbutazone induced chromosomal aberrations in CHO cells in the presence, but not the absence, of exogenous metabolic activation; no induction of sister chromatid exchanges was observed in CHO cells in the presence or absence of activation. Conclusions: Under the conditions of these 2-year gavage studies, there was equivocal evidence of carcinogenic activity of phenylbutazone for male F344/N rats, as shown by the occurrence of small numbers of renal tubular cell adenomas or carcinomas. There was some evidence of carcinogenic activity for female F344/N rats, as shown primarily by the occurrence of two rare transitional cell carcinomas in the top dose group; none has ever been seen in vehicle control or untreated control female rats. Tubular cell adenomas may have been associated with the administration of phenylbutazone to female rats. There was some evidence of carcinogenic activity for male B6C3F1 mice, as shown by the increased incidence of hepatocellular adenomas or carcinomas (combined). There was no evidence of carcinogenicity for female B6C3F1 mice administered phenylbutazone in corn oil by gavage at doses of 150 or 300 mg/kg. Phenylbutazone was also nephrotoxic to rats, as shown by the dose-related increase in the severity of age-related nephropathy, necrosis of the renal papilla, and mineralization of the collecting ducts in the papilla. Synonyms: 4-butyl-1,2-diphenyl-3,5-pyrazolidinedione; 3,5-dioxo-1,2-diphenyl-4-n-butylpyrazolidine Trade Names: There have been over 100 registered trade names including: Anerval; Azobutil; Bizolin 200; Butacote; Butadion; Butagesic; Butazolidin; Chembutazone; Equi Bute; Flexazone; Fenibutol; G 13,871; Pyrazolidin; Reumazol; Robizon-V; Uzone
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PMID:NTP Toxicology and Carcinogenesis Studies of Phenylbutazone (CAS No. 50-33-9) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1269 37

Dimethylarsinic acid (DMA(V), cacodylic acid), a foliar herbicide, was administered in the diet to B6C3F1 mice (at dose levels of 0, 8, 40, 200, and 500 ppm) and to F344 rats (at dose levels of 0, 2, 10, 40, and 100 ppm) for 2 years, according to US EPA guidelines. In mice, there were no treatment-related tumors observed at any site. Treatment-related progressive glomerulonephropathy and nephrocalcinosis were observed in the kidneys in both sexes. The incidence of vacuolation of the epithelium in the urinary bladder was increased in both sexes, but was not associated with cytotoxicity, necrosis or hyperplasia. Based on non-neoplastic lesions found in the urinary bladder, the NOEL for mice was assessed to be 40 ppm in males and 8 ppm in females. In rats, treatment-related mortality occurred early in the study in five males in the 100 ppm group and in one male in the 40 ppm group. Papillomas and carcinomas with degeneration of the urothelium, necrosis and urothelial cell hyperplasia, were found in the urinary bladders of both sexes. In male rats, one papilloma was found in each of the 10 and 40 ppm groups; one urothelial cell carcinoma was found in the 2 ppm group and two in the 100 ppm group. Four papillomas and six urothelial cell carcinomas were found in the female 100 ppm group. Non-neoplastic treatment-related kidney lesions were confined to the 40 and 100 ppm levels and included necrosis, pyelonephritis, medullary nephrocalcinosis and tubular cystic dilation, hyperplasia of the epithelial lining of the papilla, and pelvic urothelial cell hyperplasia. All of these kidney changes appear to be related to an increase in the aging nephropathy of the rat. Dose-related increases in the height of the thyroid follicular epithelium were also noted in males and females, however, such changes reflect an adaptive response of the thyroid to decreased levels of circulating thyroid hormone, rather than an adverse effect. Based on the kidney and bladder lesions, the NOEL for non-neoplastic and neoplastic lesions was considered to be 10 ppm in males and females. Based on these studies, DMA(V) is carcinogenic only in rats and only at relatively high doses, with the urinary bladder as the target organ. Female rats appear to be more sensitive to the effects of DMA(V) than male rats. DMA(V) is not carcinogenic in mice.
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PMID:Dimethylarsinic acid: results of chronic toxicity/oncogenicity studies in F344 rats and in B6C3F1 mice. 1667 51