Naslov
Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME

Autori
Drmic, Domagoj ; Kolenc, Danijela ; Ilic, Spomenko ; Bauk, Lara ; Sever, Marko ; Zenko Sever, Anita ; Luetic, Kresimir ; Suran, Jelena ; Seiwerth, Sven ; Sikiric, Predrag

Izvornik
World Journal of Gastroenterology (1007-9327) 23 (2017), 29; 5304-5312

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pregledni rad, znanstveni

Ključne riječi
BPC 157, Celecoxib, L-arginine, N(G)-nitro-L-arginine methyl ester, Rats

Sažetak
AIM To counteract/reveal celecoxib-induced toxicity and NO system involvement. METHODS Celecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine (100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L- arginine methyl ester (L-NAME)] (5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter. RESULTS This high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L- arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization (L- arginine) and NO system antagonization (L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157 (at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L- NAME application and in all the BPC 157 groups (L- arginine + BPC 157 ; L-NAME + BPC 157 ; L-NAME + L- arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition (counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade (equally counteracting the noxious effects of celecoxib + L-NAME). CONCLUSION BPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs’ post- surgery application and NO system involvement.

Izvorni jezik
Engleski

POVEZANOST RADA