Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of 40 days of treatment with Cyclosporine A (CSA) on plasma and urine free amino acids were investigated in sham-operated (C) and partially nephrectomized (Pnx) female Fischer 344 rats. High Dose CSA (30 mg/kg/day ip) was associated with reduced weight gain, increased plasma urea nitrogen, and hypoproteinemia in C and Pnx animals. These animals also demonstrated increased plasma levels of alanine, markedly reduced levels of tryptophan, and an increase in urinary excretion of methylhistidines. C but not Pnx animals also showed a significant increase in plasma serine and a decrease in plasma taurine. CSA treatment of group C resulted in a progressive aminoaciduria involving substrates of the neutral and acidic renal amino acid transport systems; however, the renal excretion of taurine and beta-alanine by these animals was markedly reduced as compared to vehicle treated controls. High dose CSA exacerbated aminoaciduria in Pnx animals, but in this group, the excretion of beta amino acids was also increased. Our findings demonstrate that chronic CSA toxicity in rodents with normal renal function is characterized by increased muscle protein catabolism, significant reductions in plasma tryptophan, and an apparent decrease in whole body taurine pools. With the exception of the taurine abnormalities. CSA treatment had similar effects on Pnx animals; however, in this group, CSA-induced pathological changes were superimposed on the changes due to renal insufficiency per se. CSA toxicity as identified by the parameters investigated in this study was no more severe in Pnx animals with moderate chronic renal insufficiency than in controls with intact renal function.
Exp Mol Pathol 1991 Aug
PMID:Free amino acids during chronic cyclosporine A toxicity in intact and partially nephrectomized rats. 188 71

Adriamycin widely used in the treatment of neoplastic conditions is nephrotoxic. In the present study the protective effect of lipoic acid was investigated in adriamycin-induced nephrotoxicity in adult male albino Wistar rats. Adriamycin-induced nephrotoxicity was characterized by hyperlipidemia, proteinuria, and hypoproteinemia, by decreased activities of the enzymes N-acetyl-beta-D-glucosaminidase and cathepsin D, by increased lipid peroxidation and decreases in serum catalase and glutathione activities, and by increased urinary and serum urea, creatinine and urinary glycosaminoglycans. Pretreatment with lipoic acid restored the changes, indicating that lipoic acid is renoprotective in adriamycin nephrotoxicity.
Mol Cell Biochem 2003 May
PMID:The influence of lipoic acid on adriamycin-induced hyperlipidemic nephrotoxicity in rats. 1284 41

A deficiency of citrin, which is encoded by the SLC25A13 gene, causes both adult-onset type II citrullinemia (CTLN2) and neonatal intrahepatic cholestasis (NICCD). We analyzed 16 patients with NICCD to clarify the clinical features of the disease. Severe intrahepatic cholestasis with fatty liver was the most common symptom, but the accompanying clinical features were variable, namely; suspected cases of neonatal hepatitis or biliary atresia, positive results from newborn screening, tyrosinemia, failure to thrive, hemolytic anemia, bleeding tendencies and ketotic hypoglycemia. Laboratory data showed elevated serum bile acid levels, hypoproteinemia, low levels of vitamin K-dependent coagulation factors, and hypergalactosemia. Hypercitrullinemia was detected in 11 out of 15 patients examined. Most of the patients were given a lactose-free and/or medium chain triglycerides-enriched formula and lipid-soluble vitamins. The prognosis of the 16 patients is going fairy well at present, but we should observe these patients carefully to see if they manifest any symptom of CTLN2 in the future.
Mol Genet Metab 2004 Nov
PMID:Clinical heterogeneity of neonatal intrahepatic cholestasis caused by citrin deficiency: case reports from 16 patients. 1554 92

Although ATRA is a potent renoprotective agent, relatively little is known regarding the mechanisms of its action. The present study was designed to further elucidate the mechanisms of ATRA's action to GS rats and compare that with the beneficial effect of benazepril. Male SD rats weighting 160 to 200g were used in this study. GS was induced by unilateral nephrectomy and intravenous injection of adriamycin (6mg/kg). They were divided randomly 20 ones per group into GS group, GS treated with ATRA (20mg/kg/day) group, and GS treated with benazepril (10mg/kg/day) group. The other 20 ones were taken as sham-operation group, injected normal saline into caudal vein. 12weeks later, all rats were subjected to sacrifice. As expected, the GS group exhibited significant lower serum TP and Alb, and higher BUN, Cr and proteinuria than those of the sham group. Administration of ATRA or benazepril did ameliorate these above disorders of biochemical parameters in GS rats. Extensive renal damage was observed in the GS group, such as mononuclear infiltration, mesangial proliferation, focal segment glomerular sclerosis, and tubulointerstitial fibrosis. The pathological changes in both ATRA and benazepril group were alleviated remarkably. Semiquantitative GSI was used to evaluate the degree of GS in all groups. GSI was significantly higher in the GS group than in sham group. GSI decreased from 21.9+/-6.7 in the GS group to 6.9+/-2.8 in the ATRA group and 7.0+/-2.7 in benazepril group respectively. However, no significant difference in GSI between rats treated with ATRA and rats treated with benazepril was found. RT-PCR analysis revealed the renal expression of alpha-SMA mRNA was induced substantially in GS group as compared to sham group, which could be offset completely by ATRA or benazepril administration. However, expression level of alpha-SMA mRNA in GS rats treated with ATRA was identical to that in GS rats treated with benazepril. We also examined immunohistochemical staining for renal alpha-SMA, TGF-beta1, Col IV, and FN in this model. Weak staining was observed in some glomerulus, mesangial cells, and tubular interstitium of sham rats. Staining was markedly enhanced in the majority of glomerulus, mesangial cells, and tubular interstitium of untreated GS rats. Compared with untreated GS animals, intensity and extent of staining for renal alpha-SMA, TGF-beta1, Col IV, and FN were markedly reduced in glomerulus, mesangial cells, and tubular interstitium of GS rats treated with either ATRA or benazepril. However, no significant differences existed between ATRA and benazepril with respect to the glomerular and tubulointerstitial staining scores. Interestingly, our data documented some differences of therapeutic capacities between ATRA and benazepril. In comparison with benazepril, ATRA exerted no improvement in hypoproteinemia, but more significant decrease in serum Cr level in GS rats. The reasons leading to these variations are unclear. Whatever they are, the properties of down-regulate inflammatory/proliferative programs may make ATRA an attractive potential candidate for future therapeutic use in kidney disease.
Exp Mol Pathol 2010 Aug
PMID:Beneficial effect of all-trans retinoic acid (ATRA) on glomerulosclerosis rats via the down-regulation of the expression of alpha-smooth muscle actin: a comparative study between ATRA and benazepril. 2049 35