scholarly journals Effect of nonsteroidal anti-inflammatory drugs with varying extent of COX-2–COX-1 selectivity on urinary sodium and potassium excretion in the rat

2005 ◽  
Vol 83 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Sam Harirforoosh ◽  
Fakhreddin Jamali
Keyword(s):  
Flow Rate ◽  
Urine Flow ◽  
Urinary Sodium ◽  
Urine Flow Rate ◽  
Potassium Excretion ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Sodium And Potassium ◽  
Cox 1

Nonsteroidal anti-inflammatory drugs (NSAIDs) have different selectivity to inhibit cyclooxygenase-1 (COX-1) and COX-2. Treatment with NSAIDs has been associated with kidney side effects. We compared the effect of a selected group of NSAIDs with different COX-2–COX-1 selectivities on urinary sodium and potassium excretion in rats. Each treatment with rofecoxib, celecoxib, meloxicam, diclofenac, and flurbiprofen (30, 120, 9, 30, and 125 mg/kg, respectively) and placebo was administered orally once daily for 4 days. Urine was collected 0–8 h after each dose. Urinary sodium and potassium excretion and urine flow rate were compared with placebo. As compared with placebo, rofecoxib, celecoxib, diclofenac, and flurbiprofen significantly reduced excretion rate of sodium (rofecoxib, 0.28 ± 0.02 vs. 0.41 ± 0.03; celecoxib, 0.23 ± 0.03 vs. 0.48 ± 0.04; diclofenac, 0.09 ± 0.02 vs. 0.46 ± 0.03; and flurbiprofen, 0.11 ± 0.02 vs. 0.47 ± 0.02 µmol/(min × 100 g)) and potassium (rofecoxib, 0.55 ± 0.04 vs. 0.68 ± 0.04; celecoxib, 0.50 ± 0.06 vs. 0.72 ± 0.06; diclofenac, 0.26 ± 0.05 vs. 0.67 ± 0.04; and flurbiprofen, 0.35 ± 0.05 vs. 0.62 ± 0.03 µmol/ (min × 100 g)). Rofecoxib and flurbiprofen significantly reduced urine flow rate. Meloxicam had no significant effect on either sodium and potassium excretion or on the urine flow rate. At the examined dosage level, no relationship was found between reported COX-2–COX-1 selectivity and urinary electrolytes excretion.Key words: COX-1, COX-2, kidney, NSAIDs, urinary sodium excretion.

Homeostatic potassium excretion in fed and fasted sheep

1988 ◽  
Vol 254 (2) ◽  
pp. R357-R380 ◽  
Author(s):  
L. Rabinowitz ◽  
D. M. Green ◽  
R. L. Sarason ◽  
H. Yamauchi
Keyword(s):  
Flow Rate ◽  
Urine Flow ◽  
Plasma Aldosterone ◽  
Urine Flow Rate ◽  
Potassium Excretion ◽  
Adult Sheep ◽  
Blood Ph ◽  
Low Levels ◽  
K Concentration ◽  
Filtered Load

In unanesthetized adult sheep, following intake of a daily meal, there was a peak in K excretion. The maximum and minimum rates of K excretion following meals were directly related to meal K content. On days without meals, no peak in K excretion occurred. Changes in K excretion on fed and fast days occurred without changes in the low levels of plasma aldosterone and were poorly correlated with urine or blood pH, urine flow rate, Na excretion, or the filtered load of K, but they correlated well with fractional K excretion. Plasma K did not change on fast days. Plasma K increased on some, but not all, fed days. Increases in plasma K that occurred on fed days were insufficient to account for the concurrent kaliuresis. Infusion of aldosterone or isotonic NaCl failed to alter K excretion in fed or fasted sheep. Infusion of isotonic NaCl + aldosterone hypertonic Na2SO4 + aldosterone increased K excretion in fasted but not fed sheep. Infusion of K in the rumen of fed and fasted sheep elevated rumen K concentration and led to increases in K excretion that could not be explained by increases in plasma K. The mechanisms responsible for the homeostatic changes in K excretion on fed and fast days were not ascertained but may importantly depend on sensors of enteric K content.

Synthesis and evaluation of new benzimidazole-based COX inhibitors: a naproxen-like interaction detected by STD-NMR

RSC Advances ◽  
2015 ◽  
Vol 5 (61) ◽  
pp. 49098-49109 ◽  
Author(s):  
Luísa C. R. Carvalho ◽  
Daniela Ribeiro ◽  
Raquel S. G. R. Seixas ◽  
Artur M. S. Silva ◽  
Mariana Nave ◽  
...  
Keyword(s):  
Pharmacological Activity ◽  
Cox Inhibitors ◽  
Cyclooxygenase 1 ◽  
Inflammatory Drugs ◽  
Std Nmr ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Non-steroidal anti-inflammatory drugs exert their pharmacological activity through inhibition of cyclooxygenase 1 and 2 (COX-1 and COX-2).

Effect of Posture on Renal Lithium Clearance

1976 ◽  
Vol 51 (1) ◽  
pp. 103-105
Author(s):  
D. F. Smith ◽  
M. Shimizu
Keyword(s):  
Renal Clearance ◽  
Flow Rate ◽  
Urine Flow ◽  
Urine Flow Rate ◽  
Lithium Clearance ◽  
Healthy Men ◽  
The Subject ◽  
First Time ◽  
Sodium And Potassium ◽  
Lying Down

1. Renal lithium clearance in healthy men was elevated while the subject was reclining, decreased upon standing and increased upon lying down during 45–60 min tests. 2. Parallel changes in renal clearance of creatinine, sodium and potassium, and urine flow rate occurred in response to the changes in posture. 3. The findings demonstrate for the first time that posture is a factor that can influence lithium excretion. Control of posture during lithium excretion tests is recommended.

scholarly journals In silico study of anthocyanin and ternatin flavonoids for the treatment of inflammation-related diseases using molecular docking analysis

Food Research ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 780-785
Author(s):  
Y.T. Wijaya ◽  
A. Yulandi ◽  
A.W. Gunawan ◽  
Yanti
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Active Site ◽  
In Silico ◽  
Protein Crystal ◽  
Drug Candidate ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Inflammatory markers such as cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), and prostaglandin (PEG) are widely known as major targets in discovering natural anti-inflammatory drugs for the treatment of inflammationrelated diseases. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin are mostly used at present, however, some NSAIDS have been reported to cause gastrointestinal side effect due to ligand-protein interaction. Molecular docking is a promising tool to study such modes of interaction. In this study, we evaluated the potential use of anthocyanin and ternatin flavonoids as natural anti-inflammatory agents for treatment of inflammatory-related diseases using in silico molecular docking assay. Automated docking study using Protein-Ligand ANT System (PLANTS) and AutoDock Vina was performed with various ligand molecules, including ibuprofen, anthocyanin, and ternatin against the protein crystal structures of COX-1, COX-2, iNOS, and MPO. The in silico data demonstrated that ibuprofen bound effectively to the active site of COX-1 and MPO with minimum binding energy, yet the compound required more energy to bind the active site of COX-2. Ternatin flavonoid was bound to COX-2 and iNOS with minimum binding energy. In terms of binding energy, anthocyanin flavonoid was found to be effective for inhibiting COX-1, COX-2, and iNOS. These results suggested that anthocyanin and ternatin flavonoids may potentially be developed as anti-inflammatory drug candidate for the treatment of inflammatory-related diseases.

scholarly journals Motion – Cyclo-oxygenase-2 Selective Nonsteroidal Anti-Inflammatory Drugs are as Safe as Placebo for the Stomach: Arguments Against the Motion

2003 ◽  
Vol 17 (5) ◽  
pp. 335-338 ◽  
Author(s):  
Andreas Maetzel
Keyword(s):  
Low Dose ◽  
Traditional Nsaid ◽  
Suitable Alternative ◽  
Randomized Controlled ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Upper Gastrointestinal ◽  
Cox 1

Cyclo-oxygenase (COX) exists in two isoforms, COX-1 and COX-2, that direct the synthesis of prostaglandins, prostacyclin and thromboxane. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both isoenzymes, resulting in damage to the mucosa of the stomach and duodenum, but also in cardioprotection. Selective COX-2 inhibitors are less likely to damage the upper gastrointestinal tract, as has been shown by large, randomized, controlled trials. Specifically, the newer agents are superior to ibuprofen and naproxen in this regard, but celecoxib and diclofenac were not significantly different in patients who were not also taking low-dose acetylsalicylic acid. These studies did not include a placebo arm, however, and controlled comparisons of COX-2 inhibitors with placebo have not enlisted enough subjects to demonstrate conclusively that they are equally safe. Selectivity for the COX-2 isoform affords protection against upper gastrointestinal toxicity possibly at the expense of the cardioprotective effect of traditional NSAIDs. This might explain the higher rate of nonfatal myocardial infarction in patients who aregiven rofecoxib compared with naproxen. A traditional NSAID, combined with either misoprostol or a proton pump inhibitor, is still a suitable alternative to selective COX-2 inhibitors for the treatment of arthritis.

scholarly journals NSAIDs and heart failure: A dangerous relationship

2018 ◽  
Vol 88 (2) ◽  
Author(s):  
Raffaele Rotunno ◽  
Igino Oppo ◽  
Gabriele Saetta ◽  
Pietro Aveta ◽  
Sergio Bruno
Keyword(s):  
Heart Failure ◽  
Urinary Flow ◽  
Vascular Thrombosis ◽  
Cyclooxygenase 1 ◽  
Vasodilatory Action ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Cox 1

One of the potential cardiotoxic action of anti-inflammatory drugs is the occurrence of heart failure (HF), due to their effects on fluid retention and blood pressure. The risk of hospitalization for HF is roughly doubled for both Coxibs, cyclooxygenase-1 (COX-1) and cyclooxygenase- 2 (COX-2) inhibitors, and all the conventional nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs are also associated with a risk of vascular thrombosis, which for NSAIDs is different in relation to their different ability to inhibit COX-1 and COX-2. The cardiovascular toxicity of these drugs in the direction of HF follow different pathways respect to their related vascular thrombosis toxicity and involves, in particular, the renal prostaglandins, PGE2 and prostacyclin, mostly synthesized by COX-2. In the kidneys the PGs perform a direct vasodilatory action, e.g. by means of non-contrasting angiotensin mechanisms, and for this reason nimesulide effects on renal microcirculation are independent from the prevalence of intrarenal renin angiotensin aldosterone system (RAAS) activity. Conversely, nimesulide reduces sodium tubular urinary flow only in presence of intrarenal RAAS.

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