Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enteric excretion of oxalate was studied in rats with chronic renal failure (CRF) by measuring the magnitude and direction of oxalate fluxes in vitro across short-circuited preparations of distal colon in Ussing chambers. The net absorptive flux of oxalate that is characteristic of colonic tissues removed from control rats was significantly changed to a net secretory flux in CRF rats. Injecting CRF rats with a specific angiotensin II (AngII) receptor (AT1) antagonist, losartan, results in a reversal of the CRF-induced net secretory flux (-13.87+/-0.08 pmol x cm(-2) x h(-1)) to an absorptive flux (+7.32+/-3.68 pmol x cm(-2) x h(-1)) by normalizing the unidirectional fluxes of oxalate. Similarly, oxalate fluxes were normalized across CRF colonic tissues by acute, in vitro application of losartan to the serosal bathing solution. It was also possible to simulate the CRF-induced secretory flux of oxalate (Jsm) in vitro across colonic tissues removed from control rats. Serosal application of AngII at 10(-6), 10(-5), and 10(-4) M resulted in significant increases in the s-->m flux of oxalate (increasing deltaJsm = 4.06+/-1.2, 8.41+/-0.94, and 13.8+/-3.8 pmol x cm(-2) x h(-1), respectively). Taken together, these results suggest that CRF-induced oxalate secretion is at least partly mediated by AngII, which is consistent with previous findings of a twofold upregulation of AT1 receptors in CRF colonic mucosa.
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PMID:Regulatory aspects of oxalate secretion in enteric oxalate elimination. 1054 Dec 56

In this study, we investigated the protective effect of losartan as an AT1 receptor antagonist by evaluating the expression of apoptosis-regulatory genes that contribute to the progressive damage in the renal tubules of hyperoxaluric rats. Rats were divided into 4 groups of 10 each; control (C), ethylene glycol (EG), ethylene glycol + losartan (EG + L) and Losartan (L). For 4 weeks 0.8% EG, as a precursor for oxalate, was administered to EG and EG + L and losartan (300 mg/l) was administered to groups EG + L and L. Urine and blood samples were collected for biochemical determination. Bcl-2, bax, caspase-3 and TGF-beta 1 antibodies were used for immunohistochemistry. Apoptosis was determined by TUNEL method. A marked increase in urinary oxalate levels of the rats in EG and EG + L groups was found. In the EG group a diffuse amount of oxalate crystals into the tubular lumina and interstitium in the cortex was observed. In the EG group GBM thickening, interstitial fibrosis and tubular atrophy with infiltration of mononuclear cell findings reduced in the EG + L group were presented as well. In the EG group, immunoreactivity of TGF-beta 1 was increased in glomeruli and tubuli. In the EG + L group, immunoreactivity of TGF-beta 1 was decreased compared to the EG group. Bax expression increased in the renal tubules of EG group and reduced in the EG + L group comparing to the control. In the EG + L group, the immunoreactivity of bcl-2 was increased in glomeruli. In EG + L treated group, number of caspase-3 immunopositive cells were decreased compared to all groups (P < 0.01). Apoptotic cells were increased in the EG-treated group compared to the other groups. Decreased apoptotic cell number was observed in the EG + L compared to the EG group (P < 0.01). Our findings suggest that losartan may provide a beneficial effect against tubulointerstitial damage and decrease renal tubular apoptosis caused by hyperoxaluria.
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PMID:Antiapoptotic effect of angiotensin-II type-1 receptor blockade in renal tubular cells of hyperoxaluric rats. 2015 Nov 16