Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:5116-45-0 (GPT)
 2,404 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Haloanilines are commonly used as chemical intermediates in the manufacture of a wide range of products. The purpose of this study was to examine the in vivo nephrotoxic and hepatotoxic potentials of the 3-haloanilines. The in vitro effects of the 3-haloanilines on renal function were also examined. In the in vivo experiments, male Fischer 344 rats (four rats/group) were administered a single intraperitoneal (i.p.) injection of an aniline hydrochloride (1.0 or 1.25 mmol kg-1) or vehicle. Renal and hepatic function were monitored at 24 and/or 48 h post-treatment. None of the 3-haloanilines were potent nephrotoxicants at either dose level. The greatest effects on renal function were observed following administration of 3-chloroaniline at a dose of 1.25 mmol kg-1 (oliguria, glucosuria, hematuria, decreased p-aminohippurate accumulation by renal cortical slices and increased blood urea nitrogen concentration). 3-Chloroaniline also was the only aniline compound to increase plasma ALT/GPT activity at 48 h. In the in vitro experiments, the ability of an aniline (10(-5) - 10(-3) M) to decrease organic ion accumulation in renal cortical slices from untreated rats was examined. The decreasing order of in vitro nephrotoxic potential was 3-iodoaniline > 3-bromoaniline > 3-chloroaniline > aniline > 3-fluoroaniline. These results indicate that the 3-haloanilines are not potent nephrotoxicants or hepatotoxicants at sublethal doses. In addition, the reasons why the 3-haloanilines have different orders of nephrotoxic potential in vivo and in vitro are not clear at this time.
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PMID:Acute renal and hepatic effects induced by 3-haloanilines in the Fischer 344 rat. 778 60

Halogenated anilines and aminophenols are nephrotoxicants and hepatotoxicants in mammals. The purpose of this study was to determine the in vivo and in vitro nephrotoxic and hepatotoxic potential of 4-amino-2,6-dichlorophenol, a putative metabolite of 3,5-dichloroaniline. In the in vivo experiments, male Fischer 344 rats (four/group) were administered a single intraperitoneal (i.p.) injection of 4-amino-2,6-dichlorophenol (0.25, 0.38 or 0.50 mmol/kg) or vehicle (dimethylsulfoxide (DMSO), 1.0 ml/kg) and renal and hepatic function monitored for 48 h. Only minor changes in function or morphology were observed in the 0.25 mmol/kg treatment group. However, in the 0.38 mmol/kg treatment group evidence of both nephrotoxicity and hepatotoxicity were evident. Nephrotoxicity was characterized by increased proteinuria, glucosuria, hematuria, elevated blood urea nitrogen (BUN) concentration and kidney weight, decreased p-aminohippurate (PAH) accumulation and proximal tubular necrosis in the corticomedullary region of the kidney. Hepatotoxicity was characterized by elevated plasma alanine aminotransferase (ALT/GPT) activity and liver weight. Animals administered the 0.5 mmol/kg dose died within 24 h. In the in vitro experiments, the effect of 4-amino-2,6-dichlorophenol on organic ion accumulation, gluconeogenesis and lactate dehydrogenase (LDH) leakage was quantitated in liver and/or renal cortical slices. Organic anion accumulation was inhibited in renal cortical slices by 4-amino-2,6-dichlorophenol bath concentrations of 5 x 10(-6) M or higher, while organic cation uptake was decreased at 4-amino-2,6-dichlorophenol bath concentrations of 1 x 10(-5) M or greater. Renal and hepatic pyruvate-stimulated gluconeogenesis were inhibited and renal LDH leakage increased at 4-amino-2,6-dichlorophenol bath concentrations of 5 x 10(-5) M or greater. Increased LDH leakage from liver slices was not observed. These results demonstrate that 4-amino-2,6-dichlorophenol is a nephrotoxicant and hepatotoxicant in vivo and in vitro and that the kidney is more susceptible to 4-amino-2,6-dichlorophenol toxicity than the liver.
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PMID:In vivo and in vitro 4-amino-2,6-dichlorophenol nephrotoxicity and hepatotoxicity in the Fischer 344 rat. 802 37

Twenty three pregnancy-induced hypertension (PIH) patients with ascites were treated in Beijing Obstetrics and Gynecology Hospital from Jan. 1981 to April 1992. The incidence of ascites in PIH was 1.9/1000 in total in this study, and 21.6/1000 in severe PIH. Clinical manifestations showed an early onset of PIH at 29.4 +/- 4.8 weeks, and ascites occurred at 32.4 +/- 7.4 weeks. There were 18 cases out of 23 who had no routine antenatal care, all of them had complications with IUGR. Laboratory studies: ascites showed transudate in all of them except one with chronic nephritis exhibiting milky appearance. 10% of patients had abnormal complete blood count (CBC) and 13%-17% abnormal electrolytes. 17.0% of the patients had GPT > 30IU, 21.0% urea nitrogen > 35 g/L, 95.7% had plasma albumin < 35 g/L. The ratio of A/G was < 1.5 in all patients. We conclude that once PIH was 1.5 in all patients. We conclude that once PIH was complicated by ascites, it can not be cured by active treatment. It is an indication for termination of pregnancy. After delivery the ascites and pleural effusion gradually disappeared in 2 weeks. Perinatal mortality rate was as high as 42.1% because of premature induced labor and IUGR.
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PMID:[Complication of ascites in pregnancy-induced hypertension]. 803 24

This study examined the contribution of biotransformation by the mixed function oxidase system on hepatic and renal toxicity of 1,2-dichlorobenzene (1,2-DCB). Male Fischer 344 (F344) rats (190-250 g) were pretreated with phenobarbital (PB), beta-naphthoflavone (BNF), pyridine (PYR), piperonyl butoxide (PiBx) or vehicle prior to the administration of 2 or 3 mmol/kg of 1,2-DCB. Pair-fed control animals were treated with corn oil, (1 ml/kg). Plasma alanine amino-transaminase (ALT/GPT) was increased in a dose-dependent manner by 1,2-DCB. Pretreatment with PB, BNF or PB pretreatment prior to 1,2-DCB administration increased hepatic toxicity within 24 h. Toxicity was characterized by increased ALT/GPT activity and increased liver weight. Acute administration of 1,2-DCB produced renal alterations within 24 h. Renal toxicity was characterized by altered blood urea nitrogen (BUN) concentration and decreased renal cortical slice accumulation of p-aminohippurate (PAH) 24 h after injection of 3 mmol/kg 1,2-DCB. Pretreatment with PB, BNF or PYR increased the renal toxicity of 2 and 3 mmol/kg 1,2-DCB. Conversely, pretreatment with PiBx to inhibit P450 activity slightly decreased the hepatic and renal toxicity of 1,2-DCB. These results establish that the kidney was a target organ for 1,2-DCB toxicity and that the proximal tubule was a site of damage. Additionally, these studies indicate induction of P450 isozymes increased the hepatic and renal toxicity of 1,2-DCB. Further studies are needed to examine the specific role of P450 in generation of toxicity.
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PMID:Modification of P450 activity and its effect on 1,2-dichlorobenzene toxicity in Fischer 344 rats. 831 47

Chlorinated anilines are widely used chemical intermediates which have been shown to be nephrotoxicants and hepatotoxicants. A major metabolic pathway for the chloroanilines is via acetylation of the amino group to form chlorocetanilides. The purpose of this study was to examine the hepato- and nephrotoxic potential of the three monochloroacetanilides to determine if N-acetylation is an important biotransformation step for activation or detoxification of the chloroanilines in organ-directed toxicity. In one set of experiments, male Fischer 344 rats (4 rats/group) were injected intraperitoneally (i.p.) with a chloroacetanilide (CAA) (0.5, 1.0 or 1.5 mmol/kg) or vehicle and renal function monitored for 24 or 48 h. Liver function and tissue morphology also were determined at 24 or 48 h. None of the CAA were marked nephrotoxicants at doses of 0.5 or 1.0 mmol/kg. However, 4-CAA (1.5 mmol/kg) induced an increase in blood urea nitrogen concentration and kidney weight at 24 h and 3-CAA (1.5 mmol/kg) was lethal within 24 h. The decreasing order of in vivo nephrotoxic potential was found to be 4-CAA > or = 3-CAA > 2-CAA. Based on the elevation of ALT/GPT activity at 48 h, the order of hepatotoxic potential was found to be 4-CAA > 3-CAA, 2-CAA. In a second set of experiments, the in vitro effect of the chloroacetanilides on organic ion transport by renal cortical slices was examined. Both 3- and 4-CAA decreased organic ion accumulation at bath concentrations of 10(-5) M or greater, while 2-CAA had no effect at concentrations up to 10(-3) M. These results demonstrate that the order of nephrotoxic and hepatotoxic potential among the chloroacetanilide isomers is different than among the chloroanilines and that the chloroacetanilides were generally less potent as hepatotoxicants or nephrotoxicants than the corresponding chloroaniline. In addition, N-acetylation appears to be a detoxification rather than a bioactivation step in chloroaniline-induced liver or kidney injury.
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PMID:Renal and hepatic toxicity of monochloroacetanilides in the Fischer 344 rat. 831 48

We analyzed historical control data of clinical pathology testings provided by sixty-seven member companies of the Japan Pharmaceutical Manufacturers Association covering study populations of approximately 7,000 rats/sex, 5,000 dogs/sex, and 700 monkeys/sex. This paper assesses the relationship between conditions of sample collection, methods of measurement, etc. and potential factors contributing to variations in reference data, based on weighted means and standard deviations thereof derived from data for rats, dogs and monkeys for those parameters measured using methods most common to the participating facilities. Parameters included erythrocyte count (RBC), hematocrit (Ht), hemoglobin concentration(Hb), reticulocyte count (Rt), platelet count, total leukocyte count (WBC), differential leukocyte count (%WBC), coagulation time (activated partial thromboplastin time: APTT, prothrombin time: PT), and serum/plasma levels of GOT, GPT, ALP, LDH, glucose, cholesterol, triglycerides (TG), total protein, albumin, urea nitrogen (UN), creatinine, sodium (Na), potassium (K), calcium (Ca), chloride (Cl), inorganic phosphorus (Ip), and CPK. Analyses of the data revealed species differences in RBC, Ht, Rt, platelet count, WBC, %WBC, ALP, LDH, glucose, cholesterol, TG, total protein, UN, creatinine, Ca, Ip, and CPK. There were strain differences in rats in platelet count, WBC, GOT, ALP, UN, creatinine, and CPK. Sex differences were noted for Hb, Ht, WBC, ALP, glucose, cholesterol, TG, total protein, A/G ratio, UN, and Ip. Age differences were observed with RBC, Hb, Ht, Rt, %WBC, GOT, GPT, ALP, LDH, cholesterol, TG total protein, Ip, and CPK. APTT, PT, ALP, glucose, TG and UN were found to be subject to the influence of fasting/feeding. In rats, Ht, WBC, CPK and K showed differences by the site of bleeding. Observed values for LDH and CPK varied with specimen type, plasma or serum; serum assay values showed greater variation than plasma values.
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PMID:Clinical pathology reference ranges of laboratory animals. Working Group II, Nonclinical Safety Evaluation Subcommittee of the Japan Pharmaceutical Manufacturers Association. 835 5

Studies were conducted to examine acute hepatic and renal toxicity of dichlorobenzene (DCB) structural isomers. Male Fischer 344 (F344) rats were injected with 2, 3 or 4 mmol kg-1 of 1,2-DCB, 1,3-DCB or 1,4-DCB (o-, m-, p-). Pair-fed control (PFC) animals were injected (i.p.) with corn oil (1 ml kg-1). Hepatic and renal toxicity was quantitated 24 h after injection of DCB or vehicle. Plasma transaminase (ALT/GPT) activity was increased (P < 0.05) by 1,2-DCB as a function of dose administered. Centrilobular necrosis was observed in rats treated with 1,2-DCB while morphology was relatively normal in rats treated with m- or p-DCB. Administration of (2 or 4 mmol kg-1) 1,3-DCB or 1,4-DCB did not alter kidney weight or blood urea nitrogen (BUN) levels. Renal cortical slice accumulation of p-aminohippurate (PAH) was decreased (P < 0.05) by (2 and 4 mmol kg-1) 1,3-DCB and (3 and 4 mmol kg-1) 1,2-DCB while accumulation of the cation tetraethylammonium (TEA) was decreased by 4 mmol kg-1 1,4-DCB. (TEA). The results of these studies demonstrated that ortho substitution enhanced hepatic and renal toxicity. The results also would suggest that the liver was more sensitive than the kidney for DCB toxicity.
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PMID:Acute hepatic and renal toxicity of dichlorobenzene isomers in Fischer 344 rats. 844 Aug 69

Toxic effects of gentamicin administration (10-80 mg/kg body weight, subcutaneously (s.c.), once daily for 7 days) on several enzyme activities of kidney and duodenal mucosa together with other parameters were compared between male rats and mice. In Wistar rat kidney, tubular brush border Mg(2+)-dependent, HCO3(-)-stimulated ATPase (Mg(2+)-HCO3(-)-ATPase) activity was inhibited by 40-80 mg/kg gentamicin in an almost dose-dependent manner with no changes in microsomal Mg(2+)-Na(+)-K(+)-ATPase activity. Cytosol carbonic anhydrase (CA) activity was inhibited only by 80 mg/kg gentamicin. In rat duodenal mucosa, Mg(2+)-HCO3(-)-ATPase and CA activities were unchanged by any dose of gentamicin. Rat serum urea nitrogen (UN), GOT and GPT concentrations and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity were significantly increased by 80 mg/kg gentamicin. In ddY mice, however, almost all parameters described above were unaffected by gentamicin except for the urinary NAG activity which was increased only by 80 mg/kg gentamicin. The concentration of gentamicin in cytosol of rat whole kidney was approximately 3.4-fold higher compared with that in mouse kidney after 80 mg/kg treatment. In light microscopic analysis, 80 mg/kg gentamicin produced necrosis in the greater part of rat kidney proximal tubuli with no pathological findings in mouse kidney. In conclusion, Mg(2+)-HCO3(-)-ATPase activity in brush border membrane of rat proximal tubuli was selectively damaged in gentamicin nephrotoxicity, indicating that the rats are the suitable model for studies of gentamicin nephrotoxicity in humans.
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PMID:Comparison of gentamicin nephrotoxicity between rats and mice. 856 86

A 13-week oral toxicity study of beta-cyclodextrin was carried out in F344 rats at the dose levels of 10, 5, 2.5, 1.25, 0.6 and 0% in powdered diet. Each group consisted of 10 males and 10 females. All animals survived at the end of the experiment, while a slight decrease in body-weight gain was observed in males of the 10%- and 5%-groups. Dose-dependent increases in serum levels of GOT, GPT and alkaline phosphatase were observed in treated animals of both sexes, and increases in serum levels of urea nitrogen and relative liver weights in treated males. Histopathologically, a dose-dependent increase in the severity of inflammatory cell infiltration was seen in the liver of treated animals, focal hepatocellular necrosis being detected in both sexes of the 10%-group and females of the 5%-group. These findings indicate that beta-cyclodextrin causes hepatocellular injury to rats when it is orally administered.
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PMID:[Hepatic lesions in F344 rats treated orally with beta-cyclodextrin for 13 weeks]. 871 26

Effect of intravenous prostagrandin E1 (PGE1) during and after surgery on postoperative hepatorenal functions in senile patients was evaluated in 36 elective surgical patients ranged in age from 60 to 85 years. The patients with carcinoma of the stomach underwent total or subtotal gastrectomy under isoflurane anesthesia. These patients were devided into two groups. Eighteen patients received intravenous PGE1 at a rate of 0.03-0.13 micrograms.kg-1.min-1 during surgery and 0.03 microgram.kg.min-1 after surgery until 9:00 am on the first operative day. The remaining 18 patients did not receive PGE1 and served as the control group. Serum GOT and GPT levels in both groups increased significantly at emergence from anesthesia compared with the preanesthetic levels and then declined to the preanesthetic levels on the 3rd postoperative day. Thereafter they increased significantly again on the 7th postoperative day. Serum GOT levels in the PGE1 administered group were significantly lower than those in the control group at the emergence from anesthesia. Serum GPT levels in the PGE1 group tended to be lower than those in the control group on awakening from anesthesia and on the first postoperative day. Serum gamma-GTP levels were stable postoperatively but they increased significantly on the 7th postoperative day in both groups. Serum bilirubin levels were within normal limits in both groups. Postoperative serum levels of urea nitrogen and creatinine were at the preanesthetic levels in both groups. Our findings suggest that continuous intravenous administration of PGE1 during and after surgery is beneficial in attenuating hepatic injury in senile patients for gastrectomy. However, protective effect of PGE1 on postoperative renal function was found to be vague in this study.
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PMID:[Intravenous infusion of prostagrandin E1 during and after gastrectomy on postoperative hepato-renal functions in senile patients]. 872 Nov 40


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