[Non-steroidal anti-inflammatory drug induced gastropathy and preventive effects of teprenone on the gastropathy in rats].
OBJECTIVE
To construct the model of non-steroidal anti-inflammatory drug (NSAID) induced gastropathy and observe the preventive effects of Teprenone on it in rats.


METHODS
Ninety-one male Sprague-Dawley (SD) rats were divided into normal saline group, model group (I) and prophylaxis group (II). Group I includes four subgroups (Ia, Ib, Ic, Id) treated by indomethacin (5 mgxkg(-1)xd(-1)), combination of indomethacin (5 mgxkg(-1)xd(-1)) and prednisone (10 mgxkg(-1)xd(-1)), celecoxib (100 mgxkg(-1)xd(-1)) and combination of celecoxib (100 mgxkg(-1)xd(-1)) and prednisone (10 mgxkg(-1)xd(-1)) respectively. Group II also includes four subgroups (IIa, IIb, IIc, IId) pretreated by teprenone (12 mgxkg(-1)xd(-1)) compared with group I. Lesion index (LI), pathohistology index, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) mRNA detected by RT-PCR were observed after 4 days.


RESULTS
Compared with normal saline group, LI (11.00 (1.00 - 22.5), 8.50 (0.75 - 14.50), 11.00 (3.50 - 14.75), P < 0.01) of three model subgroups (Ia, Ib, Id), and pathohistology indexes (1.00 (0.00 - 1.25), 2.00 (0.00 - 5.00), 1.00 (0.00 - 3.00), 2.00 (0.00 - 2.00), P < 0.01) of the whole model group increased significantly (P < 0.05). Compared with corresponding model subgroups, LIs (0.00 (0.00 - 0.25), 1.00 (0.00 - 1.50), 0.00 (0.00 - 0.00), 0.00 (0.00 - 1.00), P < 0.05) and pathohistology indexes (0.00 (0.00 - 0.00), 0.00 (0.00 - 0.50), 0.00 (0.00 - 0.25), 0.00 (0.00 - 0.50), P < 0.05) of prophylaxis subgroups were decreased significantly (P < 0.05). There was obvious difference in LI between Ic and Ia as well as between Ic and Id (P < 0.05). Compared with normal saline group, COX-1 mRNA expression of the groups (Ia, Ib, Id, IIa, IIb and IId) increased (0.384 +/- 0.031, 0.354 +/- 0.026, 0.753 +/- 0.049, 0.366 +/- 0.035, 0.381 +/- 0.036, 0.766 +/- 0.401, P < 0.001) while COX-2 mRNA expression of the above groups decreased statistically (0.483 +/- 0.056, 0.448 +/- 0.046, 0.461 +/- 0.050, 0.479 +/- 0.032, P < 0.001).


CONCLUSIONS
These results suggested gastric mucosa lesions could be resulted from COX-2 inhibitors but better than those induced by traditional NSAID. Prednisone could promote the risk in NSAID induced gastropathy. In addition to COX-1 inhibition, other factors might also involved in NSAID induced gastropathy. Teprenone could prevented from NSAID induced gastropathy but the actions might be not associated with COXs.
Ma
Juan
J
Division of Gastroenterology, The First Affiliated Hospital, Sun Yan-sen University, Guangzhou 510080, China.
Yuan
Gang
G
Chen
Min-hu
MH
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D000068579:Celecoxib; D051545:Cyclooxygenase 1 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D004224:Diterpenes / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D011241:Prednisone / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013272:Stomach Diseases / Q000139:chemically induced / Q000517:prevention & control*; D013449:Sulfonamides / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D004224:Diterpenes; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000068579:Celecoxib; C031049:geranylgeranylacetone; D011241:Prednisone