학술논문
PENTADECAPEPTIDE BPC 157 SHORTENS DURATION OF TETRACAINE- AND OXYBUPROCAINE-INDUCED CORNEAL ANESTHESIA IN RATS/PENTADEKAPEPTID BPC 157 SKRACUJE TRAJANJE ANESTEZIJE ROZNICE IZAZVANE TETRAKAINOM I OKSIBUPROKAINOM KOD STAKORA
Original Scientific Paper
Original Scientific Paper
Document Type
Report
Author
Source
Acta Clinica Croatica. September 2020, Vol. 59 Issue 3, p394, 13 p.
Subject
Language
English
ISSN
0353-9466
Abstract
Introduction Our study was focused on counteracting corneal anesthesia using the stable gastric pentadecapeptide BPC 157, N(gamma)-nitro-L-arginine methyl ester (L-NAME) and/or L-arginine in rats (1-13). After the stable gastric pentadecapeptide [...]
We focused on the relationship of 0.5% tetracaine- and 0.4% oxybuprocaine-induced corneal anesthesia in rats, and pentadecapeptide BPC 157 (0.4 [micro]g/eye), along with nitric oxide synthase (NOS) inhibitor N(gamma)-nitro-L-arginine methyl ester (L-NAME) (0.1 mg/eye) and/or NOS substrate L-arginine (2 mg/eye), applied in the form of eye drops. We assessed corneal sensitivity recovery (Cochet-Bonnet esthesiometer), corneal lesion elimination (staining with 10% fluorescein) and decrease in tear volume (Schirmer test). BPC 157 administration had a full counteracting effect. Recovery also occurred in the presence of NOS blockade and NOS substrate application. L-arginine eventually shortened duration of corneal insensitivity and exerted corneal lesion counteraction (and counteraction of tetracaine-induced decrease of tear volume) only in earlier but not in later period. L-NAME application led to longer duration of corneal insensitivity, increase in corneal lesions and decrease in tear volume. When L-NAME and L-arginine were applied together, they antagonized each other's effect. These distinctions may indicate particular NOS involvement (corneal insensitivity vs. corneal lesion along with tear production), distinctively affected by the administration of NO agents. However, additional BPC 157 co-administration would re-establish counteraction over topical ophthalmic anesthetic-induced effect, be it in its early or late course. We suggest BPC 157 as an antidote to topical ophthalmic anesthetics. Key words: BPC 157; Tetracaine; Oxybuprocaine; Corneal anesthesia; NOS; Rats U ovom istrazivanju ispitivali smo meduodnos anestezije roznice uzrokovane 0,5% tetrakainom odnosno 0,4% oksi-buprokainom i pentadekapeptida BPC 157 (0,4 [micro]g/oko) u kombinaciji s inhibitorom nitrid oksida L-NAME (0,1 mg/oko) i/ili supstratom nitrid oksida L-argininom (2 mg/oko) primijenjenim u obliku kapi za oci. Procjenjivali smo anesteziju roznice (Cochet-Bonnetov esteziometar), nestajanje lezija roznice (bojenje 10% fluoresceinom) te volumen nastajanja suza (Schirmerov test). Ucinak potpunog ponistavanja anestezije roznice uocen je u skupinama koje su primale BPC 157. Oporavak je takoder nastupio u skupinama koje su primale i supstrat i blokator nitrid oksida. L-arginin skracuje vrijeme neosjetljivosti roznice, a uoceno je i smanjenje lezija roznice te ponistavanje smanjenja lucenja suza, ali samo u ranijem kracem raz-doblju, dok se kasnije taj ucinak gubi. L-NAME je uzrokovao produzenje vremena neosjetljivosti roznice kao i povecanje lezija roznice te dodatno smanjenje stvaranja suza. Kada se L-arginin i L-NAME daju zajedno njihov ucinak se ponistava. Opazene razlike mogu ukazivati na odredeni utjecaj i ukljucenost nitrid oksida (neosjetljivost roznice naspram nastajanja lezija roznice i stvaranja suza), sto je pokazano primjenom supstrata/blokatora nitrid oksida. Medutim, u bilo kojoj kombinaciji prije ili kasnije, dodatak BPC 157 doveo bi do ponistavanja ucinka primijenjenih anestetika. Kljucne rijeci: BPC 157; Tetrakain; Oksibuprokain; Anestezija roznice; NOS; Stakori
We focused on the relationship of 0.5% tetracaine- and 0.4% oxybuprocaine-induced corneal anesthesia in rats, and pentadecapeptide BPC 157 (0.4 [micro]g/eye), along with nitric oxide synthase (NOS) inhibitor N(gamma)-nitro-L-arginine methyl ester (L-NAME) (0.1 mg/eye) and/or NOS substrate L-arginine (2 mg/eye), applied in the form of eye drops. We assessed corneal sensitivity recovery (Cochet-Bonnet esthesiometer), corneal lesion elimination (staining with 10% fluorescein) and decrease in tear volume (Schirmer test). BPC 157 administration had a full counteracting effect. Recovery also occurred in the presence of NOS blockade and NOS substrate application. L-arginine eventually shortened duration of corneal insensitivity and exerted corneal lesion counteraction (and counteraction of tetracaine-induced decrease of tear volume) only in earlier but not in later period. L-NAME application led to longer duration of corneal insensitivity, increase in corneal lesions and decrease in tear volume. When L-NAME and L-arginine were applied together, they antagonized each other's effect. These distinctions may indicate particular NOS involvement (corneal insensitivity vs. corneal lesion along with tear production), distinctively affected by the administration of NO agents. However, additional BPC 157 co-administration would re-establish counteraction over topical ophthalmic anesthetic-induced effect, be it in its early or late course. We suggest BPC 157 as an antidote to topical ophthalmic anesthetics. Key words: BPC 157; Tetracaine; Oxybuprocaine; Corneal anesthesia; NOS; Rats U ovom istrazivanju ispitivali smo meduodnos anestezije roznice uzrokovane 0,5% tetrakainom odnosno 0,4% oksi-buprokainom i pentadekapeptida BPC 157 (0,4 [micro]g/oko) u kombinaciji s inhibitorom nitrid oksida L-NAME (0,1 mg/oko) i/ili supstratom nitrid oksida L-argininom (2 mg/oko) primijenjenim u obliku kapi za oci. Procjenjivali smo anesteziju roznice (Cochet-Bonnetov esteziometar), nestajanje lezija roznice (bojenje 10% fluoresceinom) te volumen nastajanja suza (Schirmerov test). Ucinak potpunog ponistavanja anestezije roznice uocen je u skupinama koje su primale BPC 157. Oporavak je takoder nastupio u skupinama koje su primale i supstrat i blokator nitrid oksida. L-arginin skracuje vrijeme neosjetljivosti roznice, a uoceno je i smanjenje lezija roznice te ponistavanje smanjenja lucenja suza, ali samo u ranijem kracem raz-doblju, dok se kasnije taj ucinak gubi. L-NAME je uzrokovao produzenje vremena neosjetljivosti roznice kao i povecanje lezija roznice te dodatno smanjenje stvaranja suza. Kada se L-arginin i L-NAME daju zajedno njihov ucinak se ponistava. Opazene razlike mogu ukazivati na odredeni utjecaj i ukljucenost nitrid oksida (neosjetljivost roznice naspram nastajanja lezija roznice i stvaranja suza), sto je pokazano primjenom supstrata/blokatora nitrid oksida. Medutim, u bilo kojoj kombinaciji prije ili kasnije, dodatak BPC 157 doveo bi do ponistavanja ucinka primijenjenih anestetika. Kljucne rijeci: BPC 157; Tetrakain; Oksibuprokain; Anestezija roznice; NOS; Stakori