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

Drmić, Domagoj and Kolenc, Danijela and Ilić, Spomenko and Bauk, Lara and Sever, Marko and Zenko Sever, Anita and Luetić, Krešimir and Šuran, Jelena and Seiwerth, Sven and Sikirić, Predrag (2017) Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME. World Journal of Gastroenterology, 23 (29). pp. 5304-5312. ISSN 1007-9327

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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.

Item Type: Article
Additional Information: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
MeSH: Animals ; Anti-Ulcer Agents / therapeutic use ; Antidotes / therapeutic use ; Arginine / therapeutic use ; Brain / drug effects ; Brain / pathology ; Celecoxib / administration & dosage ; Celecoxib / toxicity ; Chemical and Drug Induced Liver Injury / drug therapy ; Chemical and Drug Induced Liver Injury / etiology ; Chemical and Drug Induced Liver Injury / pathology ; Cyclooxygenase 2 Inhibitors / administration & dosage ; Cyclooxygenase 2 Inhibitors / toxicity ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Therapy, Combination / methods ; Humans ; Liver / drug effects ; Liver / pathology ; Male ; NG-Nitroarginine Methyl Ester / pharmacology ; Nitric Oxide / metabolism ; Nitric Oxide Synthase / metabolism ; Peptide Fragments / therapeutic use ; Proteins / therapeutic use ; Rats ; Rats, Wistar ; Stomach / drug effects ; Stomach / pathology ; Stomach Ulcer / chemically induced ; Stomach Ulcer / drug therapy ; Stomach Ulcer / pathology
Departments: Katedra za farmakologiju
Katedra za patologiju
Depositing User: Martina Žužak
Status: Published
Kolenc, DanijelaUNSPECIFIED
Zenko Sever, AnitaUNSPECIFIED
Luetić, KrešimirUNSPECIFIED
Sikirić, PredragUNSPECIFIED
Date: 7 August 2017
Date Deposited: 28 Feb 2018 13:41
Last Modified: 18 Aug 2020 07:45
Related URLs:
URI: http://medlib.mef.hr/id/eprint/2812

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