Comparative study on the effects of indomethacin and nabumetone on renal function in anaesthetized and conscious rats

Rao, G.Janardhana and Singh, Harbindar Jeet (2004) Comparative study on the effects of indomethacin and nabumetone on renal function in anaesthetized and conscious rats. Comparative study on the effects of indomethacin and nabumetone on renal function in anaesthetized and conscious rats. (Submitted)

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Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely prescribed agents in the treatment of pain, fever and inflammation ( 1 ). They exert their antiinflammatory, analgesic and antipyretic effects through the inhibition of prostaglandin synthesis by blocking cyclooxygenase (COX) activity, a major enzyme in the biosynthesis of all prostaglandins (2). Prostaglandins are ubiquitous in their distribution throughout the body and function for most part as "local hormones". Kidney is extremely acti·Je in the biosynthesis and mechanism of prostaglandins. These compounds participate in several processes in renal physiology, including autoregulation of renal blood flow and glomerular filtration rate, modulation of renin release, tubular ion transport and water metabolism(3). COX is a key enzyme regulating the formation of prostaglandins from arachidonic acid. Recently however, COX was discovered to have two isoform namely COX- 1 and COX-2 ( 4 ). These are derived from different genes but share -60°/o amino acid identity. The expression patterns of COX-1 and COX-2 genes are quite different (5). COX-1 is normally expressed in the gastrointestinal tract, kidney and platelets and thought to participate in housekeeping function. It appears to be responsible for mediating the production of thromboxane and prostaglandins. Under the influence of COX-1, prostaglandins maintain the integrity of the gastric mucosa, mediate normal platelet function and regulate renal blood flow during states of hemodynamic stress (6). The isoenzyme COX-2 is primarily associated with inflammation (7). Cytokines and growth factors increase the expression of COX-2 at inflammatory sites, producing prostaglandins that mediate inflammation, pain and fever. The discovery of the COX-2 isoenzyme has led to believe that COX-2 selective inhibition would provide the potent anti-inflammatory, analgesic and antipyretic effects that have been associated with the traditional NSAIDs with less side effects especially on renal function(8). Traditional NSAIDs such as ibuprofen, indomethacin, aspirin and naproxen which inhibit both COX-1 and COX-2 are known to produce deleterious effects on renal function. particularly durirg haemodynamically stressful situations (9). This includes patients and individuals with decreased effective blood volume causesd by cardiac failure ( 1 0), liver cirrhosis with ascites ( 11 ), renal insufficiency ( 12) and hypertension (13). Responses to these hemodynamic challenges include stimulation of the renin-angiotensin-aldosterone axis, with enhanced production of renin, the vasoconstrictive angiotensin II and aldosterone, which promotes sodium, water and chloride reabsorption and elevated sympathetic outflow, which further tend to promote vascular tone (14). In these situations, prostaglandins promote compensatory vasodilation of renal vascular beds to ensure an adequate blood supply and preclude acute functional deterioration of the kidney (15). But NSAIDs blunted these prostaglandins production and may cause further marked decreases in renal blood flow, glomerular filtrcltion rate (GFR) and renal excretion of sodium and water, hyperkalemia and hyponatriemia (16). However, little information exists regarding the effects of COX-2 inhibition on renal function.

Item Type: Article
Uncontrolled Keywords: Anti-Inflammatory
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Kampus Kesihatan (Health Campus) > Pusat Pengajian Sains Perubatan (School of Medical Sciences) > Article
Depositing User: Mr Abdul Hadi Mohammad
Date Deposited: 26 Feb 2020 08:35
Last Modified: 26 Feb 2020 08:35

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