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

Znanstveni rad - Izvorni znanstveni rad

• Autor: Domagoj Drmić
• Autor: Danijela Kolenc
• Autor: Spomenko Ilić
• Autor: Lara Bauk
• Autor: Marko Sever
• Autor: Anita Zenko Sever
• Autor: Krešimir Luetić
• Autor: Jelena Šuran
• Autor: Sven Seiwerth
• Autor: Predrag Sikirić
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Kliničke medicinske znanosti

Sažetak (engleski)

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.

• Ključne riječi (engleski): 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
• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran
• Verzija publikacije: Objavljena verzija rada (izdavačev PDF)
• Naslov časopisa: World Journal of Gastroenterology
• Brojčani podaci: vol. 23, br. 29, str. 5304-5312
• p-ISSN: 1007-9327
• DOI: https://doi.org/10.3748/wjg.v23.i29.5304
• URN:NBN: urn:nbn:hr:105:155023
• Datum objave publikacije: 2017-08-07
• URL dokumenta: https://doi.org/10.3748/wjg.v23.i29.5304
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup
• Datum i vrijeme pohrane: 2024-03-28 09:06:46