Comparative study on the effects of indomethacin and nabumetone on renal function in anaesthetized and conscious rats
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) acti...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Pusat Pengajian Sains Kesihatan, Universiti Sains Malaysia
2004
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| Subjects: | |
| Online Access: | http://eprints.usm.my/46361/1/GP...A%20Comparative%20Study%20On%20The%20Effects%20Of%20Indomethacin%20And%20Nabumetone%20On%20Renal%20Function%20In%20Anesthetized%20And%20Conscious%20Rats...2005...OCR.pdf |
| _version_ | 1825905546359734272 |
|---|---|
| author | Rao, G.Janardhana Singh, Harbindar Jeet |
| author_facet | Rao, G.Janardhana Singh, Harbindar Jeet |
| author_sort | Rao, G.Janardhana |
| collection | USM |
| description | 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. |
| first_indexed | 2024-03-06T15:36:05Z |
| format | Article |
| id | usm.eprints-46361 |
| institution | Universiti Sains Malaysia |
| language | English |
| last_indexed | 2024-03-06T15:36:05Z |
| publishDate | 2004 |
| publisher | Pusat Pengajian Sains Kesihatan, Universiti Sains Malaysia |
| record_format | dspace |
| spelling | usm.eprints-463612020-02-26T08:35:59Z http://eprints.usm.my/46361/ Comparative study on the effects of indomethacin and nabumetone on renal function in anaesthetized and conscious rats Rao, G.Janardhana Singh, Harbindar Jeet RM Therapeutics. Pharmacology 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. Pusat Pengajian Sains Kesihatan, Universiti Sains Malaysia 2004 Article NonPeerReviewed application/pdf en http://eprints.usm.my/46361/1/GP...A%20Comparative%20Study%20On%20The%20Effects%20Of%20Indomethacin%20And%20Nabumetone%20On%20Renal%20Function%20In%20Anesthetized%20And%20Conscious%20Rats...2005...OCR.pdf 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) |
| spellingShingle | RM Therapeutics. Pharmacology Rao, G.Janardhana Singh, Harbindar Jeet Comparative study on the effects of indomethacin and nabumetone on renal function in anaesthetized and conscious rats |
| title | Comparative study on the effects of
indomethacin and nabumetone on renal function in
anaesthetized and conscious rats |
| title_full | Comparative study on the effects of
indomethacin and nabumetone on renal function in
anaesthetized and conscious rats |
| title_fullStr | Comparative study on the effects of
indomethacin and nabumetone on renal function in
anaesthetized and conscious rats |
| title_full_unstemmed | Comparative study on the effects of
indomethacin and nabumetone on renal function in
anaesthetized and conscious rats |
| title_short | Comparative study on the effects of
indomethacin and nabumetone on renal function in
anaesthetized and conscious rats |
| title_sort | comparative study on the effects of indomethacin and nabumetone on renal function in anaesthetized and conscious rats |
| topic | RM Therapeutics. Pharmacology |
| url | http://eprints.usm.my/46361/1/GP...A%20Comparative%20Study%20On%20The%20Effects%20Of%20Indomethacin%20And%20Nabumetone%20On%20Renal%20Function%20In%20Anesthetized%20And%20Conscious%20Rats...2005...OCR.pdf |
| work_keys_str_mv | AT raogjanardhana comparativestudyontheeffectsofindomethacinandnabumetoneonrenalfunctioninanaesthetizedandconsciousrats AT singhharbindarjeet comparativestudyontheeffectsofindomethacinandnabumetoneonrenalfunctioninanaesthetizedandconsciousrats |