Inhibition of Dehydrogenases by Salicylate

Hines, W. J. W.; Smith, M. J. H.

doi:10.1038/201192a0

Cited by 40 publications

(10 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The glucose level–decreasing effects of interleukin-1 β blockade support a general strategy to targeting inflammation, albeit using an independent anti-inflammatory approach (36, 37). Salicylate has additional potential mechanisms to consider, including effects on mitochondrial dehydrogenases (38, 39), transcription factors in addition to nuclear factor- κ B (40-42), and cellular kinases (43-49). Recently, salicylate has also been shown to inhibit 11- β hydroxysteroid dehydrogenase type 1 in adipose tissue (50) and to stimulate adenosine monophosphate–activated protein kinase (51).…”

Section: Discussionmentioning

confidence: 99%

Salicylate (Salsalate) in Patients With Type 2 Diabetes

Goldfine

Fonseca²,

Jablonski³

et al. 2013

Ann Intern Med

221

129

View full text Add to dashboard Cite

Background Short-duration studies show that salsalate improves glycemia in type 2 diabetes mellitus (T2DM). Objective To assess 1-year efficacy and safety of salsalate in T2DM. Design Placebo-controlled, parallel trial; computerized randomization and centralized allocation, with patients, providers, and researchers blinded to assignment. (ClinicalTrials.gov: NCT00799643) Setting 3 private practices and 18 academic centers in the United States. Patients Persons aged 18 to 75 years with fasting glucose levels of 12.5 mmol/L or less (≤225 mg/dL) and hemoglobin A1c (HbA1c) levels of 7.0% to 9.5% who were treated for diabetes. Intervention 286 participants were randomly assigned (between January 2009 and July 2011) to 48 weeks of placebo (n = 140) or salsalate, 3.5 g/d (n = 146), in addition to current therapies, and 283 participants were analyzed (placebo, n = 137; salsalate, n = 146). Measurements Change in hemoglobin A1c level (primary outcome) and safety and efficacy measures. Results The mean HbA1c level over 48 weeks was 0.37% lower in the salsalate group than in the placebo group (95% CI, −0.53% to −0.21%; P < 0.001). Glycemia improved despite more reductions in concomitant diabetes medications in salsalate recipients than in placebo recipients. Lower circulating leukocyte, neutrophil, and lymphocyte counts show the anti-inflammatory effects of salsalate. Adiponectin and hematocrit levels increased more and fasting glucose, uric acid, and triglyceride levels decreased with salsalate, but weight and low-density lipoprotein cholesterol levels also increased. Urinary albumin levels increased but reversed on discontinuation; estimated glomerular filtration rates were unchanged. Limitation Trial duration and number of patients studied were insufficient to determine long-term risk–benefit of salsalate in T2DM. Conclusion Salsalate improves glycemia in patients with T2DM and decreases inflammatory mediators. Continued evaluation of mixed cardiorenal signals is warranted. Primary Funding Source National Institutes of Health.

show abstract

Section: Discussionmentioning

confidence: 99%

Salicylate (Salsalate) in Patients With Type 2 Diabetes

Goldfine

Fonseca²,

Jablonski³

et al. 2013

Ann Intern Med

221

129

View full text Add to dashboard Cite

show abstract

“…The enzyme DT-diaphorase, which has been suggested as an important enzyme in vitamin K reduction, was found to be sensitive to salicylate inhibition. Salicylate inhibition of several pyridine nucleotide-linked dehydrogenases has been reported (Hines & Smith 1964;Smith 1966;Smith & Dawkins 1971). The sensitivity of DT-diaphorase to salicylate is several times greater than any previously reported instance of enzyme inhibition by this drug.…”

Section: Discussionmentioning

confidence: 96%

The effects of salicylate on enzymes of vitamin K metabolism

Hildebrandt

Suttie

1983

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

The mechanism of salicylate-induced hypoprothrombinaemia has been investigated in the rat. Salicylate administration produced an increase in the percentage of the total liver vitamin that was present as vitamin K 2,3-epoxide, but the addition of salicylate did not influence vitamin K epoxide reductase activity in-vitro. Neither did it influence vitamin K-dependent carboxylase or vitamin K epoxidase activity. Both cytosolic and microsomal DT-diaphorase activities were, however, inhibited about 50% by 75 microM sodium salicylate. Salicylate inhibition was also observed when vitamin K quinone and NADH or dithiothreitol were used to support carboxylation. To achieve 50% inhibition required 0.5 mM salicylate with NADH as a reductant and 4 mM salicylate when dithiothreitol was the reductant. These results suggest that the main effect of salicylate on vitamin K metabolism is to inhibit quinone reductases and may be useful in explaining the inhibition of the biosynthesis of vitamin K-dependent clotting factors that occurs in salicylate-induced hypothrombinaemia. These data also demonstrate that the percentage of total liver vitamin present as vitamin K epoxide can be increased by agents that do not have a direct effect on the vitamin K epoxide reductase in-vitro.

show abstract

“…Effects of ASA on the intermediary metabolism have been known since 1943, when von Euler and Ahlstrom showed that salicylate inhibited glucose and lactate dehydrogenases in uitro. Inhibition of several dehydrogenases in the Krebs cycle has since been demonstrated (Kaplan, Kennedy and Davis 1954, Bryant, Smith and Hincs 1963, Hines and Smith 1964. Inhibition of transaminases and an uncoupling cffect on oxidative phosphorylation reactions have also been found (Huggins, Smith andMoses 1961, Brody 1956).…”

Section: Discussionmentioning

confidence: 96%

The Disappearance of Acetylsalicylic Acid (ASA) in Aqueous Solution from the Cat Stomach and its Influence on the Transmucosal Ion Transport in the Innervated Non‐secreting Stomach

Frenning¹

1971

Acta Physiologica Scandinavica

View full text Add to dashboard Cite

FRENNINC, B. The disappearance of acetylsalicylic acid ( A S A ) in aqueous solutionfrom the cat stomach and its influence o n the transmucosal ion transport in the innervated, non-secreting stomach. Acta physiol. scand. 197 1. 83. 235-246.During instillation of aqueous solutions of acetylsalicylic acid (ASA) into innervated, nonsecreting whole stomach pouches in the cat, parallel decreases in the salicylate and hydrogen

show abstract

Inhibition of Dehydrogenases by Salicylate

Cited by 40 publications

References 3 publications

Salicylate (Salsalate) in Patients With Type 2 Diabetes

Salicylate (Salsalate) in Patients With Type 2 Diabetes

The effects of salicylate on enzymes of vitamin K metabolism

The Disappearance of Acetylsalicylic Acid (ASA) in Aqueous Solution from the Cat Stomach and its Influence on the Transmucosal Ion Transport in the Innervated Non‐secreting Stomach

Contact Info

Product

Resources

About