Avtor/Urednik		Drmić, Domagoj; Kolenc, Danijela; Ilić, Spomenko; Bauk, Lara; Sever, Marko; Zenko Sever, Anita; Luetic, Kresimir; Suran, Jelena; Seiwerth, Sven; Sikirić, Predrag
Naslov		Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME
Tip		članek
Vol. in št.		Letnik 23, št. 29
Leto izdaje		2017
Obseg		str. 5304-5312
ISSN		1007-9327 - World Journal of Gastroenterology : Shijie Wei-Changbingxue Zazhi
Jezik		eng
Abstrakt		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 [micro]g/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.
Proste vsebinske oznake		BPC 157 celecoxib L-arginine BPC 157 celekoksib L-arginin