Guanosine prevents nuclear factor-κB nuclear translocation ameliorating experimental colitis in rats

Rosa Maria Serio, Gaetano Felice Caldara, Maria Grazia Zizzo, Annalisa Bellanca, Domenico Nuzzo, Marta Di Carlo

Risultato della ricerca: Other

Abstract

Backgroundinflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are prevalent and debilitating health problems worldwide. Due to the adverse effects of classical treatment for IBD, therapeutic options and approaches for these diseases continue to evolve. Guanosine, a guanine-based purine, is an extracellular signalling molecule that seems to exert anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. The aim of the present study was to investigate whether exogenous guanosine may have protective effects on 2,4-dinitrobenzene sulfonic acid (DNBS)-induced Colitis in rat.MethodsExperimental Colitis was induced by intrarectal administration of 0.25 ml of DNBS in 50% EtOH solution. After the induction of colitis animal received daily for 6 consecutive days i.p injection of guanosine (8 mg/kg). The effects of guanosine on DNBS-induced colitis were assessed by determination of body weight loss, stool consistency, colon weight/length, histological analysis, Furthermore the myeloperoxidase activity was biochemically evaluated and the mRNA expression of pro-inflammatory cytokines was detected by real-time quantitative reverse transcription PCR (qRT-PCR). In addition, nuclear factor-κB (NF-κB) p65 protein expression levels in colon tissues was investigated using Western blotting and markers of oxidative and nitrosative stress were detected.ResultsInflammation in DNBS-rat is characterised by symptoms of losing body weight, loose feces/watery diarrhoea, leukocyte infiltration upregulation of proinflammatory cytokines, oxidative and nitrosative stress. Treatment with guanosine (8 mg/kg) significantly ameliorated the severity of DNBS-induced colitis as evidenced by the reduction in body weight loss and in diarrhoea. Guanosine also prevented the macroscopic and microscopic damage to the colonic mucosa, and the increase in myeloperoxidase activity induced by DNBS. Furthermore, the guanosine treated colitis rats also exhibited a lower mRNA level of pro-inflammatory cytokines, namely interleukin-1β , interleukin-6 and tumour necrosis factor-α. Importantly, the ameliorative effect of guanosine was related to an inhibition of the NF-κB signalling pathway by downregulating the expression levels of NF-κB p-65, and to a reduction of DNBS increased levels of reactive oxygen species and nitrite.ConclusionOverall these results indicate that guanosine is able to alleviate colonic inflammation in DNBS- rats mainly by down-regulation of the NF-κB signalling pathway and of the production of anti-inflammatory cytokines, reactive oxygen species and nitrite. Further studies are encouraging for disclosure guanosine as a novel drug candidate for the treatment of colonic inflammation.
Lingua originaleEnglish
Pagine144-144
Numero di pagine1
Stato di pubblicazionePublished - 2018

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Guanosine
Colitis
Dinitrobenzenes
Sulfonic Acids
Cytokines
Body Weight
Nitrites
Peroxidase
Weight Loss
Diarrhea
Reactive Oxygen Species
Colon
Oxidative Stress
Anti-Inflammatory Agents
Down-Regulation
Inflammation
Messenger RNA
Disclosure
Guanine
Interleukin-1

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@conference{b6436f9080684d30a903ee9e61d589a8,
title = "Guanosine prevents nuclear factor-κB nuclear translocation ameliorating experimental colitis in rats",
abstract = "Backgroundinflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are prevalent and debilitating health problems worldwide. Due to the adverse effects of classical treatment for IBD, therapeutic options and approaches for these diseases continue to evolve. Guanosine, a guanine-based purine, is an extracellular signalling molecule that seems to exert anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. The aim of the present study was to investigate whether exogenous guanosine may have protective effects on 2,4-dinitrobenzene sulfonic acid (DNBS)-induced Colitis in rat.MethodsExperimental Colitis was induced by intrarectal administration of 0.25 ml of DNBS in 50{\%} EtOH solution. After the induction of colitis animal received daily for 6 consecutive days i.p injection of guanosine (8 mg/kg). The effects of guanosine on DNBS-induced colitis were assessed by determination of body weight loss, stool consistency, colon weight/length, histological analysis, Furthermore the myeloperoxidase activity was biochemically evaluated and the mRNA expression of pro-inflammatory cytokines was detected by real-time quantitative reverse transcription PCR (qRT-PCR). In addition, nuclear factor-κB (NF-κB) p65 protein expression levels in colon tissues was investigated using Western blotting and markers of oxidative and nitrosative stress were detected.ResultsInflammation in DNBS-rat is characterised by symptoms of losing body weight, loose feces/watery diarrhoea, leukocyte infiltration upregulation of proinflammatory cytokines, oxidative and nitrosative stress. Treatment with guanosine (8 mg/kg) significantly ameliorated the severity of DNBS-induced colitis as evidenced by the reduction in body weight loss and in diarrhoea. Guanosine also prevented the macroscopic and microscopic damage to the colonic mucosa, and the increase in myeloperoxidase activity induced by DNBS. Furthermore, the guanosine treated colitis rats also exhibited a lower mRNA level of pro-inflammatory cytokines, namely interleukin-1β , interleukin-6 and tumour necrosis factor-α. Importantly, the ameliorative effect of guanosine was related to an inhibition of the NF-κB signalling pathway by downregulating the expression levels of NF-κB p-65, and to a reduction of DNBS increased levels of reactive oxygen species and nitrite.ConclusionOverall these results indicate that guanosine is able to alleviate colonic inflammation in DNBS- rats mainly by down-regulation of the NF-κB signalling pathway and of the production of anti-inflammatory cytokines, reactive oxygen species and nitrite. Further studies are encouraging for disclosure guanosine as a novel drug candidate for the treatment of colonic inflammation.",
author = "Serio, {Rosa Maria} and Caldara, {Gaetano Felice} and Zizzo, {Maria Grazia} and Annalisa Bellanca and Domenico Nuzzo and {Di Carlo}, Marta",
year = "2018",
language = "English",
pages = "144--144",

}

TY - CONF

T1 - Guanosine prevents nuclear factor-κB nuclear translocation ameliorating experimental colitis in rats

AU - Serio, Rosa Maria

AU - Caldara, Gaetano Felice

AU - Zizzo, Maria Grazia

AU - Bellanca, Annalisa

AU - Nuzzo, Domenico

AU - Di Carlo, Marta

PY - 2018

Y1 - 2018

N2 - Backgroundinflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are prevalent and debilitating health problems worldwide. Due to the adverse effects of classical treatment for IBD, therapeutic options and approaches for these diseases continue to evolve. Guanosine, a guanine-based purine, is an extracellular signalling molecule that seems to exert anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. The aim of the present study was to investigate whether exogenous guanosine may have protective effects on 2,4-dinitrobenzene sulfonic acid (DNBS)-induced Colitis in rat.MethodsExperimental Colitis was induced by intrarectal administration of 0.25 ml of DNBS in 50% EtOH solution. After the induction of colitis animal received daily for 6 consecutive days i.p injection of guanosine (8 mg/kg). The effects of guanosine on DNBS-induced colitis were assessed by determination of body weight loss, stool consistency, colon weight/length, histological analysis, Furthermore the myeloperoxidase activity was biochemically evaluated and the mRNA expression of pro-inflammatory cytokines was detected by real-time quantitative reverse transcription PCR (qRT-PCR). In addition, nuclear factor-κB (NF-κB) p65 protein expression levels in colon tissues was investigated using Western blotting and markers of oxidative and nitrosative stress were detected.ResultsInflammation in DNBS-rat is characterised by symptoms of losing body weight, loose feces/watery diarrhoea, leukocyte infiltration upregulation of proinflammatory cytokines, oxidative and nitrosative stress. Treatment with guanosine (8 mg/kg) significantly ameliorated the severity of DNBS-induced colitis as evidenced by the reduction in body weight loss and in diarrhoea. Guanosine also prevented the macroscopic and microscopic damage to the colonic mucosa, and the increase in myeloperoxidase activity induced by DNBS. Furthermore, the guanosine treated colitis rats also exhibited a lower mRNA level of pro-inflammatory cytokines, namely interleukin-1β , interleukin-6 and tumour necrosis factor-α. Importantly, the ameliorative effect of guanosine was related to an inhibition of the NF-κB signalling pathway by downregulating the expression levels of NF-κB p-65, and to a reduction of DNBS increased levels of reactive oxygen species and nitrite.ConclusionOverall these results indicate that guanosine is able to alleviate colonic inflammation in DNBS- rats mainly by down-regulation of the NF-κB signalling pathway and of the production of anti-inflammatory cytokines, reactive oxygen species and nitrite. Further studies are encouraging for disclosure guanosine as a novel drug candidate for the treatment of colonic inflammation.

AB - Backgroundinflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are prevalent and debilitating health problems worldwide. Due to the adverse effects of classical treatment for IBD, therapeutic options and approaches for these diseases continue to evolve. Guanosine, a guanine-based purine, is an extracellular signalling molecule that seems to exert anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. The aim of the present study was to investigate whether exogenous guanosine may have protective effects on 2,4-dinitrobenzene sulfonic acid (DNBS)-induced Colitis in rat.MethodsExperimental Colitis was induced by intrarectal administration of 0.25 ml of DNBS in 50% EtOH solution. After the induction of colitis animal received daily for 6 consecutive days i.p injection of guanosine (8 mg/kg). The effects of guanosine on DNBS-induced colitis were assessed by determination of body weight loss, stool consistency, colon weight/length, histological analysis, Furthermore the myeloperoxidase activity was biochemically evaluated and the mRNA expression of pro-inflammatory cytokines was detected by real-time quantitative reverse transcription PCR (qRT-PCR). In addition, nuclear factor-κB (NF-κB) p65 protein expression levels in colon tissues was investigated using Western blotting and markers of oxidative and nitrosative stress were detected.ResultsInflammation in DNBS-rat is characterised by symptoms of losing body weight, loose feces/watery diarrhoea, leukocyte infiltration upregulation of proinflammatory cytokines, oxidative and nitrosative stress. Treatment with guanosine (8 mg/kg) significantly ameliorated the severity of DNBS-induced colitis as evidenced by the reduction in body weight loss and in diarrhoea. Guanosine also prevented the macroscopic and microscopic damage to the colonic mucosa, and the increase in myeloperoxidase activity induced by DNBS. Furthermore, the guanosine treated colitis rats also exhibited a lower mRNA level of pro-inflammatory cytokines, namely interleukin-1β , interleukin-6 and tumour necrosis factor-α. Importantly, the ameliorative effect of guanosine was related to an inhibition of the NF-κB signalling pathway by downregulating the expression levels of NF-κB p-65, and to a reduction of DNBS increased levels of reactive oxygen species and nitrite.ConclusionOverall these results indicate that guanosine is able to alleviate colonic inflammation in DNBS- rats mainly by down-regulation of the NF-κB signalling pathway and of the production of anti-inflammatory cytokines, reactive oxygen species and nitrite. Further studies are encouraging for disclosure guanosine as a novel drug candidate for the treatment of colonic inflammation.

UR - http://hdl.handle.net/10447/282143

M3 - Other

SP - 144

EP - 144

ER -