To counteract/reveal celecoxib-induced toxicity and NO system involvement. METHODSCelecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 ...To counteract/reveal celecoxib-induced toxicity and NO system involvement. METHODSCelecoxib (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. RESULTSThis 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). CONCLUSIONBPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs’ post-surgery application and NO system involvement.展开更多
The main objective is to study the role or nitric oxide (NO) in small Intestinal migratingmotor complex (MMC). Rats were implanted with strain gauges in the duobenum and jejunum forrecording the motor action of the sm...The main objective is to study the role or nitric oxide (NO) in small Intestinal migratingmotor complex (MMC). Rats were implanted with strain gauges in the duobenum and jejunum forrecording the motor action of the small intestine in fasting and red states arter intravenous infusionof N'-nitro-L-arginine methyl ester (L-NAME ), L-arginin., D-arglnine, sodium nitropusside(NaNP) and angiotensin 1 respectively. The results showed that intravenous inrusion or L-NAME,a NO synthase inhibitor, induced a fasting-like MMC motor pattern in fed rats. Infusion of NaNP, aNO donor, disrupted small intestinal MMC in fasting rats, inducing a postprandial-like motor pattern. Both fasting and postprandial, infusion of L-NAME shortened the duration or Phase I andphase Ⅱ,but didn't chang. the duration, frequency, amplitude and s,eed or Propogatiou of thephaSe, Ⅲ-argining, not D-arginine infused together with L-NAME, prevented the effect of LNAME infusion. Infusion of L-arginine, D-arginine or angioteusin Ⅰ alone didn't modify the smallintestinal motor pattern. It suggests that an inhibition of NO synthesis may be involved in the initiation of the MMC motor pattern during fasting, whereas an increase of NO output relates to the occurrence of the fed motor pattern展开更多
文摘To counteract/reveal celecoxib-induced toxicity and NO system involvement. METHODSCelecoxib (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. RESULTSThis 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). CONCLUSIONBPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs’ post-surgery application and NO system involvement.
文摘The main objective is to study the role or nitric oxide (NO) in small Intestinal migratingmotor complex (MMC). Rats were implanted with strain gauges in the duobenum and jejunum forrecording the motor action of the small intestine in fasting and red states arter intravenous infusionof N'-nitro-L-arginine methyl ester (L-NAME ), L-arginin., D-arglnine, sodium nitropusside(NaNP) and angiotensin 1 respectively. The results showed that intravenous inrusion or L-NAME,a NO synthase inhibitor, induced a fasting-like MMC motor pattern in fed rats. Infusion of NaNP, aNO donor, disrupted small intestinal MMC in fasting rats, inducing a postprandial-like motor pattern. Both fasting and postprandial, infusion of L-NAME shortened the duration or Phase I andphase Ⅱ,but didn't chang. the duration, frequency, amplitude and s,eed or Propogatiou of thephaSe, Ⅲ-argining, not D-arginine infused together with L-NAME, prevented the effect of LNAME infusion. Infusion of L-arginine, D-arginine or angioteusin Ⅰ alone didn't modify the smallintestinal motor pattern. It suggests that an inhibition of NO synthesis may be involved in the initiation of the MMC motor pattern during fasting, whereas an increase of NO output relates to the occurrence of the fed motor pattern
