Nitric oxide (NO) plays a pivotal role in main- taining balance of physiological events in many systems including the autonomic, cardiovas- cular, hematological, and pulmonary systems. Lipopolysaccharide (LPS) and pep...Nitric oxide (NO) plays a pivotal role in main- taining balance of physiological events in many systems including the autonomic, cardiovas- cular, hematological, and pulmonary systems. Lipopolysaccharide (LPS) and peptidoglycan (PGN), components of the outer cell membranes of Gram-negative bacteria and cell walls of Gram-positive bacteria respectively, are in- criminated in NO-induced septic shock. Ne- bivolol is a third generation β1- adrenoceptor blocker with a vasodilatory property attributed to enhanced availability of nitric oxide and re- duction of cellular oxidative stress through an unknown mechanism. The current study ex- plored the hypothesis that if nebivolol enhances the availability of NO, pretreatment with ne- bivolol may enhance production of NO in re- sponse to subsequent treatment with LPS and PGN, an observation that may have relevance in clinical septic shock. Groups of female BALB/c mice each containing 12 mice (6-8 weeks old) were injected intraperitoneally with LPS (30 μg/mouse), PGN (100 μg/mouse), nebivolol (0.25 μg/g, 0.35 μg/g, 0.7 μg/g), LPS and nebivolol (0.25 μg/g), LPS and nebivolol (0.35 μg/g), LPS and nebivolol (0.7 μg/g), PGN and nebivolol (0.25 μg/g), PGN and nebivolol (0.35μg/g). One group of mice was injected with saline and an- other served as control. Three mice from each group were bled 1, 3, 6 and 9 hours post-injec- tion, the blood was pooled and the nitrite serum levels, reflecting NO concentration, were de- termined using Greiss reagent. The following results were obtained: 1) Treatment with saline did not induce NO production;2) LPS induced NO production to a maximal limit of 545% at 9 hours as compared to treatment with saline;3) PGN did not induce NO production;4) nebivolol at most doses and periods (7 out of 10 deter- minations) increased NO production over a range of 18-110% as compared to treatment with saline;5) Nebivolol enhanced LPS-induced production of NO by 58% at a dose of 0.7 μg/gm at 9 hours. It is concluded that nebivolol in- duces NO production. At low doses nebivolol initially appeared to have a suppressive or no effect on NO production induced by LPS. In- crease in the dose of nebivolol resulted in augmentation of LPS-induced production of NO. PGN, in the dose tested, did not have an effect on NO production.展开更多
Some antibacterial agents have been shown to neutralize the biological properties of bacterial lipopolysaccharide (LPS). The aim of this study was to eluci- date the role of gentamicin, tobramycin, imipenem, tigecycli...Some antibacterial agents have been shown to neutralize the biological properties of bacterial lipopolysaccharide (LPS). The aim of this study was to eluci- date the role of gentamicin, tobramycin, imipenem, tigecycline, and isoniazid in affecting the production of nitric oxide (NO) induced by LPS in mice. Groups of mice were injected intraperitoneally with LPS alone, antibacterial agent alone, or LPS in combination with an antibacterial agent. Serum NO levels were determined at 1, 3, 6 and 9 hours post-injection using the Griess reagent method. Thin layer chroma- tography was performed to determine if antibacterial agent—LPS interaction had occurred. All the antibacterial agents suppressed NO production. More- over, LPS-induced production of NO was suppressed by all the antibacterial agents, tobramycin and tigecycline being the most effective at 9 hours post-injection. Blocking of any of the stages leading to NO production by the antibacterial agents is suggested. Moreover, thin layer chromatograms obtained are suggestive of LPS-antibacterial agent interactions.展开更多
文摘Nitric oxide (NO) plays a pivotal role in main- taining balance of physiological events in many systems including the autonomic, cardiovas- cular, hematological, and pulmonary systems. Lipopolysaccharide (LPS) and peptidoglycan (PGN), components of the outer cell membranes of Gram-negative bacteria and cell walls of Gram-positive bacteria respectively, are in- criminated in NO-induced septic shock. Ne- bivolol is a third generation β1- adrenoceptor blocker with a vasodilatory property attributed to enhanced availability of nitric oxide and re- duction of cellular oxidative stress through an unknown mechanism. The current study ex- plored the hypothesis that if nebivolol enhances the availability of NO, pretreatment with ne- bivolol may enhance production of NO in re- sponse to subsequent treatment with LPS and PGN, an observation that may have relevance in clinical septic shock. Groups of female BALB/c mice each containing 12 mice (6-8 weeks old) were injected intraperitoneally with LPS (30 μg/mouse), PGN (100 μg/mouse), nebivolol (0.25 μg/g, 0.35 μg/g, 0.7 μg/g), LPS and nebivolol (0.25 μg/g), LPS and nebivolol (0.35 μg/g), LPS and nebivolol (0.7 μg/g), PGN and nebivolol (0.25 μg/g), PGN and nebivolol (0.35μg/g). One group of mice was injected with saline and an- other served as control. Three mice from each group were bled 1, 3, 6 and 9 hours post-injec- tion, the blood was pooled and the nitrite serum levels, reflecting NO concentration, were de- termined using Greiss reagent. The following results were obtained: 1) Treatment with saline did not induce NO production;2) LPS induced NO production to a maximal limit of 545% at 9 hours as compared to treatment with saline;3) PGN did not induce NO production;4) nebivolol at most doses and periods (7 out of 10 deter- minations) increased NO production over a range of 18-110% as compared to treatment with saline;5) Nebivolol enhanced LPS-induced production of NO by 58% at a dose of 0.7 μg/gm at 9 hours. It is concluded that nebivolol in- duces NO production. At low doses nebivolol initially appeared to have a suppressive or no effect on NO production induced by LPS. In- crease in the dose of nebivolol resulted in augmentation of LPS-induced production of NO. PGN, in the dose tested, did not have an effect on NO production.
文摘Some antibacterial agents have been shown to neutralize the biological properties of bacterial lipopolysaccharide (LPS). The aim of this study was to eluci- date the role of gentamicin, tobramycin, imipenem, tigecycline, and isoniazid in affecting the production of nitric oxide (NO) induced by LPS in mice. Groups of mice were injected intraperitoneally with LPS alone, antibacterial agent alone, or LPS in combination with an antibacterial agent. Serum NO levels were determined at 1, 3, 6 and 9 hours post-injection using the Griess reagent method. Thin layer chroma- tography was performed to determine if antibacterial agent—LPS interaction had occurred. All the antibacterial agents suppressed NO production. More- over, LPS-induced production of NO was suppressed by all the antibacterial agents, tobramycin and tigecycline being the most effective at 9 hours post-injection. Blocking of any of the stages leading to NO production by the antibacterial agents is suggested. Moreover, thin layer chromatograms obtained are suggestive of LPS-antibacterial agent interactions.
