Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protein aldose reductase has been implicated in cataract in diabetes and galactosaemia. Recently it has been suggested that a number of non-steroidal anti-inflammatory agents have inhibitory activity against aldose reductase activity, and therefore might be used to prevent diabetic complications including cataract. Steady state kinetic experiments show that Clinoril (Sulindac sulphoxide) acts as a non-competitive inhibitor of NADPH oxidation with purified bovine lens aldose reductase, with an action that may involve binding to more than one site on the protein. As a preliminary to studying the effect on human lens and cataract, a double-masked, placebo-controlled study using random allocation into parallel groups was conducted on 20 volunteers to determine the penetration of Clinoril (Sulindac) and its metabolites into normal human red cells, and the effect of the drug on red cell NADPH-oxidising activity. It was found that while Clinoril, the sulphoxide form of the drug, and its metabolites the sulphone and the sulphide could be detected in the appropriate plasma samples (up to 36 micrograms of the sulphone/ml of plasma), very little could be detected in the red cells. There was no significant effect on red cell NADPH-oxidising activity.
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PMID:The inhibition of bovine lens aldose reductase by Clinoril, its absorption into the human red cell and its effect on human red cell aldose reductase activity. 392 May 99

Prostaglandins are ubiquitous biologically active compounds that are involved in inflammatory reactions, hemostasis, and, under certain circumstances, the maintenance of renal function. NSAIDs, which inhibit PG synthesis, are used therapeutically most often as antiinflammatory agents in conditions of inflammation and pain, mostly of a nonurologic nature. However, since NSAIDs inhibit systemic PG synthesis, administration of NSAIDs can lead to adverse side effects. For example, the gastrointestinal irritation caused by NSAIDs probably reflects removal of a cytoprotective effect of gastrointestinal PGs. Similarly, the kidney may be especially susceptible to adverse effects of NSAIDs. In diseases such as peptic ulcers, diabetes, hypertension, congestive heart failure, liver disease with ascites, and renal insufficiency, PGs seem to play a protective role in the kidney. This protective role, which results from increased synthesis of vasodilator PGs in the face of elevated vasoconstrictors, is diminished in the presence of NSAIDs. Other side effects include the antagonism by NSAIDs of the action of diuretics, such that the dose of the diuretic must be adjusted accordingly. The diuretic triamterene should not be used in conjunction with indomethacin due to several reported cases of toxicity. Another drug interaction involves the salicylates, which have been shown to diminish the uricosuric effects of probenecid and sulfinpyrazone. Likewise, since corticosteroids increase the renal clearance of salicylates, it is important to monitor the patient carefully following termination of steroid treatment in patients receiving large doses of salicylates, since this change in elimination can precipitate toxicity. In addition, the NSAIDs bind to plasma proteins and, as such, can displace or be displaced by other drugs that bind in the same manner and can result in either decreased efficacy or toxicity. Despite the fact that the kidney may not be the target of NSAID therapy, renal function may be adversely affected by NSAID treatment. It has therefore been proposed that a renal-sparing NSAID would be a very useful therapeutic agent. Sulindac (Clinoril) has been suggested to be such an agent, eg, able to inhibit systemic PG synthesis (usually monitored by measuring serum thromboxane synthesis) without an apparent effect on renal PG synthesis (monitored by measurement of urinary PGs). However, recent data have suggested that Sulindac does inhibit renal PG synthesis and does not exhibit selectivity. The reasons for the discrepancy are not clear, but may relate to the doses or time intervals examined.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Indications and contraindications for the use of nonsteroidal antiinflammatory drugs in urology. 393 61