+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

S3226, a novel NHE3 inhibitor, attenuates ischemia-induced acute renal failure in rats

, : S3226, a novel NHE3 inhibitor, attenuates ischemia-induced acute renal failure in rats. Kidney International 60(6): 2283-2289

Background. Acute renal failure (ARF) remains a major problem in clinical nephrology characterized by sudden loss of the kidney function due to ischemia, trauma, and/or nephrotoxic drugs. The current therapy of ARF is symptomatic with mortality rates exceeding 50%. The aim of this study was to investigate the effects of an intravenous infusion of S3226 (3-(2-(3-guanidino-2-methyl-3-oxopropenyl)-5-methyl-phenyl)-N-isopropylidene-2-methyl-acrylamide dihydrochloride), a selective Na+/H+ exchange subtype 3 (NHE3) blocker, in ischemia-induced ARF in rats. In a second series of experiments cytosolic pH (pHi) changes in the kidney during ARF were continuously measured by means of nuclear magnetic resonance spectroscopy (MRS). Methods. ARF was induced by bilateral occlusion of renal arteries for 40 minutes in three groups of anaesthetized Wistar rats. Control rats (N = 12) were infused with saline (6.25 mL/kg over 30 min) before occlusion and the compound groups (each N = 12) were infused with S3226 at a dose of 20 mg/kg over 30 minutes either before initiation of ischemia or immediately after release of clamps. Plasma creatinine (PCr), creatinine clearance (CCr), urine volume, sodium, and potassium excretion were determined up to seven days after release of clamps. In the second series of experiments in anaesthetized rats the left kidney was exposed by flank incision and fixed in a non-magnetic device. An inflatable cuff was positioned around the pedicle to induce ischemia without removing animals from the magnet. A double-tuned 1H-31P home-built surface coil was placed above the exposed kidney for the detection of pHi. Results. At day 1 after ischemia CCr in the control group was significantly lower as compared to S3226-treated animals (control 0.30 +- 0.05 vs. before 0.90 +- 0.26 and reperfusion 0.83 +- 0.15 mL/min/kg, respectively). PCr increased from 18 +- 0.1 mumol/L before occlusion to 245 +- 7 mumol/L in the control. The increase in PCr was significantly lower in the S3226 treated groups on days 1, 2, and 3 post-infusion. Fractional sodium excretion decreased significantly from 8.17% in the control to 1.42% and 1.88% in the treated groups. Renal pHi was significantly decreased by 0.15 units versus control during reperfusion. Histological examination of the kidneys on day 7 revealed pronounced reduction of tubular necrosis, dilatation, protein casts and cellular infiltration. Conclusions. These results demonstrate that an intravenous administration of S3226 acutely improves GFR and kidney function and structure in both treated groups. In addition, in a separate set of studies S3226 significantly decreased post-occlusion renal pHi values. Thus, the inhibition of NHE3 with S3226 may be beneficial in treatment of ischemic ARF.


PMID: 11737601

DOI: 10.1046/j.1523-1755.2001.00058.x

Other references

Okochi, M.; Joh, T.; Kataoka, H.; Suzuki, H.; Seno, K.; Okayama, N.; Yokoyama, Y.; Itoh, M., 2000: Endoscopic and histological esophagitis in patients with pharyngeal and laryngeal paresthesia. Gastroenterology 118(4 Suppl 2 Part 2): AGA A1287, April

Kudriavtsev, V.I., 2014: Problem of species in microorganisms. Trudy Instituta Mikrobiologii 1: 90-107

Hyde, G.E.; Crawford, N.M.; Campbell, W.H., 1991: The sequence of squash NADH:nitrate reductase and its relationship to the sequences of other flavoprotein oxidoreductases. A family of flavoprotein pyridine nucleotide cytochrome reductases. Nucleotide sequences were determined for cDNA clones for squash NADH:nitrate oxidoreductase (EC, which is one of the most completely characterized forms of this higher plant enzyme. An open reading frame of 2754 nucleotides began at the f...

Ohashi, O.S.; Coutinho, J.C.; Silva, O.F., 1993: Aspectos biologicos de Dinarmus basalis Rondani, 1877 Hymenoptera Pteromalidae ectoparasito de Callosobruchus maculatus Fabricius, 1775 Coleoptera Bruchidae. Anais da Sociedade Entomologica do Brasil. 31 Julho; 221: 161-167

Zhao X.; Burton J.H.; Mcbride B.W.; Rehman J.D., 1991: Lactation performance of dairy cows given either daily injections or a sustained release form of rbst. Canadian Journal of Animal Science 71(4): 1290

Soda, H.; Yoshida, I.; Aramaki, S.; Kuriya, N.; Aoki, K.; Inokuchi, T.; Yoshino, M.; Kato, H., 1996: Renal handling of methylmalonic acid in a uraemic patient with vitamin B-12-unresponsive methylmalonic acidaemia. Journal of Inherited Metabolic Disease 19(1): 90-91

Bell, P.R.; Mühlethaler, K., 1964: The Degeneration And Reappearance Of Mitochondria In The Egg Cells Of A Plant. Details are given of the elimination of mitochondria which occurs during the first 1 to 2 hours of the life of the egg of the fern Pteridium aquilinum (L.) Kuhn. During this phase the only mitochondria present are swollen and appear degenerate, bu...

Das, H.C.L., 1995: New global economic environment and India's farm exports potential. An assessment is first made of the new global economic environment and market accessibility in the context of developing countries like India. The paper goes on to provide projections of India's farm exports for the year 2005/6. The largest c...

Tan, L.Wen.; Tan, C.Seng.; Rahman, Z.A.; Goh, H-Han.; Ismail, I.; Zainal, Z., 2017: Microarray dataset of transgenic rice overexpressing iAbp57. The dataset presented in this article describes microarray experiment of <i>Auxin-binding protein 57</i>, <i>Abp57</i>-overexpressing transgenic rice. The gene expression profiles were generated using Affymetrix GeneChip®...

Mefferd, R.B.; Hale, H.B.; Shannon, I.L.; Prigmore, J.R.; Ellis, J.P., 1971: Stress responses as criteria for personnel selection: baseline study. Aerospace Medicine 42(1): 42-51