AIM: To investigate the role of Sonic hedgehog (Shh) on the course of liver ischemia and reperfusion (I/R) in rats, and the interaction between treatment with nitric oxide donor L-Arginine-methyl ester (L-Arg) and up-...AIM: To investigate the role of Sonic hedgehog (Shh) on the course of liver ischemia and reperfusion (I/R) in rats, and the interaction between treatment with nitric oxide donor L-Arginine-methyl ester (L-Arg) and up-regulation of Shh expression. METHODS: A total of 30 male Sprague-Dawley rats weighing 220-240 g were used in this study. Sham-control group (G1, n = 10): a sham operation was performed (except for liver I/R). I/R-untreated group (G2, n = 10): rats underwent liver ischemia for 1 h followed by reperfusion for 45 min. I/R-L-Arg group (G3, n = 10): after performing the same surgical procedure as in group 2, animals were treated with L-Arg. Liver tissues were taken for determination of malondialdehyde (MDA) levels, and biochemical and histological evaluations were made. RESULTS: Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and γ-glutamyltranspeptidase (GGT) activities were higher in group 2 than in group 3. MDA values and the hepatic injury score decreased in the L-Arg treated group compared to the I/R-untreated group. In group 2, the hepatocytes were swollen with marked vacuolization. Group 3 rats showed well-preserved liver parenchyma, with hepatocytes extending from the central vein. The morphology of the hepatocytes and the sinusoidal structures was normal, without any signs of congestion. Mild Shh positive immunostaining was detected in group 2 animals. The expression of immunoreactive cells was increased markedly in liver tissue from I/R-L-Arg rats.CONCLUSION: Our findings suggest that Shh molecules are critical factors in the pathophysiology of inflammatory liver injury induced by I/R. In addition, NO plays an important role in the immunohistochemical expression of these molecules.展开更多
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, ...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.展开更多
In this paper, some new results on the selective weak interaction between Na-4-tosyl-L-arginine methyl ester hydrochloride (TAME) and adenosine-5'-triphosphate (ATP) have been reported. Fluorescence spectrophotom...In this paper, some new results on the selective weak interaction between Na-4-tosyl-L-arginine methyl ester hydrochloride (TAME) and adenosine-5'-triphosphate (ATP) have been reported. Fluorescence spectrophotometry and Fourier transform infrared (FT-IR) spectroscopy were used to investigate this kind of weak interaction. In fluorescence experiments, obvious fluorescence quenching phenomena were observed when TAME was added, which indicated the weak interactions between TAME and ATP. It has been identified by fluorescence titration experiments that TAME exhibited high selectivity to ATP over ADP and AMP. FT-IR spectral results showed that an ATP-TAME adduct was formed. The experimental results indicated that the interaction sites were the guanidinium group of TAME main-chain and the γ-phosphate group of ATP, and the interaction took place through hydrogen bonding and electrostatic force. In addition, the effects of metal ions on the weak interaction between ATP and TAME, or between ATP and analogues of L-arginine were studied.展开更多
Objective: This study investigated the effects of aqueous leaf extract of Tridax procumbens (ALETP) on con- tractile activity of corpus cavernosum in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive ...Objective: This study investigated the effects of aqueous leaf extract of Tridax procumbens (ALETP) on con- tractile activity of corpus cavernosum in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive male rats. Methods: Twenty normal, adult male rats (130-150 g) were divided into four groups of five rats each. Group I (control) was given normal saline (0.6 mL/kg) and group II was given L-NAME (40 mg/kg) for 6 weeks. Groups Ill and IV also received L-NAME (40 mg/kg) for 6 weeks but were further co-treated with 100 and 200 mg/kg of ALETP, respectively, from week 4 to week 6. All treatments were given orally. Strips of corpus cavernosum from each of the four groups were exposed to increasing concentrations of acetyl~ choline (ACh) and sodium nitroprusside (SNP) (10^-9-10^-5 tool/L) after contraction with phenylephrine (10^-7 mol/L) to test for a dose-response effect, Response to potassium and calcium was also measured after cumulatively adding potassium and calcium (10-50 mmol/L) to potassium- and calcium-free organ chamber. Isometric contractions were recorded through an Ugo Basile data capsule acquisition system. Results: Mean arterial blood pressure was significantly reduced in the ALETP co-treated group compared to the control and L-NAME-only groups (P 〈 0.05). Cavernosa strips from ALETP co-treated rats exhibited significant inhibition of contraction in response to phenylephrine, potassium chloride, and calcium chlo- ride (P 〈 0.05). Relaxation in response to Ach and SNP was also significantly impaired in cavernosa strips from the L-NAME-only treated group (P 〈 0.05), while ALETP co-treated groups showed enhanced per- centage relaxation. Conclusion: ALETP treatment of L-NAME-induced hypertensive rats promotes a relaxant effect on isolated cavernosa strips. ALETP shows potential in correcting erectile dysfunction in hypertension.展开更多
文摘AIM: To investigate the role of Sonic hedgehog (Shh) on the course of liver ischemia and reperfusion (I/R) in rats, and the interaction between treatment with nitric oxide donor L-Arginine-methyl ester (L-Arg) and up-regulation of Shh expression. METHODS: A total of 30 male Sprague-Dawley rats weighing 220-240 g were used in this study. Sham-control group (G1, n = 10): a sham operation was performed (except for liver I/R). I/R-untreated group (G2, n = 10): rats underwent liver ischemia for 1 h followed by reperfusion for 45 min. I/R-L-Arg group (G3, n = 10): after performing the same surgical procedure as in group 2, animals were treated with L-Arg. Liver tissues were taken for determination of malondialdehyde (MDA) levels, and biochemical and histological evaluations were made. RESULTS: Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and γ-glutamyltranspeptidase (GGT) activities were higher in group 2 than in group 3. MDA values and the hepatic injury score decreased in the L-Arg treated group compared to the I/R-untreated group. In group 2, the hepatocytes were swollen with marked vacuolization. Group 3 rats showed well-preserved liver parenchyma, with hepatocytes extending from the central vein. The morphology of the hepatocytes and the sinusoidal structures was normal, without any signs of congestion. Mild Shh positive immunostaining was detected in group 2 animals. The expression of immunoreactive cells was increased markedly in liver tissue from I/R-L-Arg rats.CONCLUSION: Our findings suggest that Shh molecules are critical factors in the pathophysiology of inflammatory liver injury induced by I/R. In addition, NO plays an important role in the immunohistochemical expression of these molecules.
文摘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.
基金Project supported by the National Natural Science Foundation of China (No. 90210027).Acknowledgments The authors especially thank Zhide Hu in Lanzhou University for kindly allowing the use of the RF-5301PC spectrofluorophotometer (Shimadzu) in this work and Wenying He in Lanzhou University for active discussion as well as zealous help during the fluorescence experiments.
文摘In this paper, some new results on the selective weak interaction between Na-4-tosyl-L-arginine methyl ester hydrochloride (TAME) and adenosine-5'-triphosphate (ATP) have been reported. Fluorescence spectrophotometry and Fourier transform infrared (FT-IR) spectroscopy were used to investigate this kind of weak interaction. In fluorescence experiments, obvious fluorescence quenching phenomena were observed when TAME was added, which indicated the weak interactions between TAME and ATP. It has been identified by fluorescence titration experiments that TAME exhibited high selectivity to ATP over ADP and AMP. FT-IR spectral results showed that an ATP-TAME adduct was formed. The experimental results indicated that the interaction sites were the guanidinium group of TAME main-chain and the γ-phosphate group of ATP, and the interaction took place through hydrogen bonding and electrostatic force. In addition, the effects of metal ions on the weak interaction between ATP and TAME, or between ATP and analogues of L-arginine were studied.
文摘Objective: This study investigated the effects of aqueous leaf extract of Tridax procumbens (ALETP) on con- tractile activity of corpus cavernosum in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive male rats. Methods: Twenty normal, adult male rats (130-150 g) were divided into four groups of five rats each. Group I (control) was given normal saline (0.6 mL/kg) and group II was given L-NAME (40 mg/kg) for 6 weeks. Groups Ill and IV also received L-NAME (40 mg/kg) for 6 weeks but were further co-treated with 100 and 200 mg/kg of ALETP, respectively, from week 4 to week 6. All treatments were given orally. Strips of corpus cavernosum from each of the four groups were exposed to increasing concentrations of acetyl~ choline (ACh) and sodium nitroprusside (SNP) (10^-9-10^-5 tool/L) after contraction with phenylephrine (10^-7 mol/L) to test for a dose-response effect, Response to potassium and calcium was also measured after cumulatively adding potassium and calcium (10-50 mmol/L) to potassium- and calcium-free organ chamber. Isometric contractions were recorded through an Ugo Basile data capsule acquisition system. Results: Mean arterial blood pressure was significantly reduced in the ALETP co-treated group compared to the control and L-NAME-only groups (P 〈 0.05). Cavernosa strips from ALETP co-treated rats exhibited significant inhibition of contraction in response to phenylephrine, potassium chloride, and calcium chlo- ride (P 〈 0.05). Relaxation in response to Ach and SNP was also significantly impaired in cavernosa strips from the L-NAME-only treated group (P 〈 0.05), while ALETP co-treated groups showed enhanced per- centage relaxation. Conclusion: ALETP treatment of L-NAME-induced hypertensive rats promotes a relaxant effect on isolated cavernosa strips. ALETP shows potential in correcting erectile dysfunction in hypertension.
基金The work was supported by the Natural Science Foundation of Zhejiang for Talents (No. RC99038) and Fund for Outstanding Young Scientists of Zhejiang University School of Medicine.