Published online Aug 7, 2017. doi: 10.3748/wjg.v23.i29.5304
Peer-review started: February 19, 2017
First decision: April 5, 2017
Revised: May 3, 2017
Accepted: July 4, 2017
Article in press: July 4, 2017
Published online: August 7, 2017
To counteract/reveal celecoxib-induced toxicity and NO system involvement.
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.
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).
BPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs’ post-surgery application and NO system involvement.
Core tip: In rats treated with the COX-2 inhibitor celecoxib, BPC 157 (given intraperitoneally) counteracted lesion development in the stomach, liver and brain. BPC 157 treatment alongside with N(G)-nitro-L-arginine methyl ester (L-NAME) also attenuated any effect of L-NAME that would otherwise have intensified the deleterious regular course. Consistently, with exacerbation (induced by L-NAME administration) and amelioration (due to L-arginine) of gastric, liver and brain lesions, L-arginine amelioration prevailed (i.e., the gastric, liver and brain lesions were attenuated) when given together with L-NAME (L-NAME + L-arginine), an effect further reversed toward a marked beneficial effect by the addition of BPC 157 (L-NAME + L-arginine + BPC 157).