Guanosine

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R Serio - One of the best experts on this subject based on the ideXlab platform.

  • preventive effects of Guanosine on intestinal inflammation in 2 4 dinitrobenzene sulfonic acid dnbs induced colitis in rats
    Inflammopharmacology, 2019
    Co-Authors: Maria Grazia Zizzo, Domenico Nuzzo, Marta Di Carlo, Gaetano Felice Caldara, Annalisa Bellanca, R Serio
    Abstract:

    Guanosine, a guanine-based purine, is an extracellular signaling molecule exerting anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. We aimed to investigate its protective effects on 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rat. Rats were divided into five groups and colitis was induced by intracolonic instillation of DNBS (15 mg/rat). Guanosine (4 or 8 mg/kg) was administered for 6 days i.p. starting the day of the colitis induction. Body weight loss, stool consistency, colon weight/length, histological analysis, myeloperoxidase activity (MPO) and pro-inflammatory cytokine levels were assessed. Immunoblotting of nuclear factor-κB (NF-κB) p65 protein levels and detection of oxidative and nitrosative stress markers were also performed. Guanosine, in a dose-dependent manner, significantly ameliorated the severity of DNBS-induced colitis, reducing body weight loss and diarrhea incidence, preventing the DNBS-induced macroscopic and microscopic damage to the colonic mucosa, and the MPO increase. Guanosine treatment also lowered interleukin-1β, interleukin-6, and tumor necrosis factor-α mRNA levels. Importantly, Guanosine in DNBS rats down-regulated the expression of NF-κB p65 and the levels of reactive oxygen species and nitrite. In conclusion, Guanosine exerts beneficial effects in DNBS-induced colitis in rats, through modulation of colonic inflammation, downregulating of NFκB-mediated signaling.

Maria Grazia Zizzo - One of the best experts on this subject based on the ideXlab platform.

  • preventive effects of Guanosine on intestinal inflammation in 2 4 dinitrobenzene sulfonic acid dnbs induced colitis in rats
    Inflammopharmacology, 2019
    Co-Authors: Maria Grazia Zizzo, Domenico Nuzzo, Marta Di Carlo, Gaetano Felice Caldara, Annalisa Bellanca, R Serio
    Abstract:

    Guanosine, a guanine-based purine, is an extracellular signaling molecule exerting anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. We aimed to investigate its protective effects on 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rat. Rats were divided into five groups and colitis was induced by intracolonic instillation of DNBS (15 mg/rat). Guanosine (4 or 8 mg/kg) was administered for 6 days i.p. starting the day of the colitis induction. Body weight loss, stool consistency, colon weight/length, histological analysis, myeloperoxidase activity (MPO) and pro-inflammatory cytokine levels were assessed. Immunoblotting of nuclear factor-κB (NF-κB) p65 protein levels and detection of oxidative and nitrosative stress markers were also performed. Guanosine, in a dose-dependent manner, significantly ameliorated the severity of DNBS-induced colitis, reducing body weight loss and diarrhea incidence, preventing the DNBS-induced macroscopic and microscopic damage to the colonic mucosa, and the MPO increase. Guanosine treatment also lowered interleukin-1β, interleukin-6, and tumor necrosis factor-α mRNA levels. Importantly, Guanosine in DNBS rats down-regulated the expression of NF-κB p65 and the levels of reactive oxygen species and nitrite. In conclusion, Guanosine exerts beneficial effects in DNBS-induced colitis in rats, through modulation of colonic inflammation, downregulating of NFκB-mediated signaling.

Youn Bok Chung - One of the best experts on this subject based on the ideXlab platform.

  • pharmacokinetics of Guanosine in rats following intravenous or intramuscular administration of a 1 1 mixture of Guanosine and acriflavine a potential antitumor agent
    Archives of Pharmacal Research, 2008
    Co-Authors: Dae Hwan Shin, Kyu Seok Choi, Byung Suk Cho, Sukgil Song, Dongcheul Moon, Jin Tae Hong, Chongkil Lee, Youn Bok Chung
    Abstract:

    A 1:1 mixture of acriflavine (ACF; CAS 8063-24-9) and Guanosine is under evaluation in preclinical studies as a possible antitumor agent. Guanosine is known to potentiate the anti-cancer activity of ACF. We therefore investigated the pharmacokinetics of Guanosine following administration of the ACF/Guanosine mixture in rats. Rats were given Guanosine (1 or 5 mg/kg) or ACF/Guanosine (2 or 10 mg/kg) by i.v. bolus; or Guanosine (3 or 15 mg/kg) or ACF/Guanosine (6 or 30 mg/kg) by i.m. injection. We found that Guanosine was rapidly cleared from the blood and transferred to tissues after i.m. administration of ACF/Guanosine. The mean plasma half-lives (t1/2) at the α and β phases were 0.091 and 6.86 h, or 0.09 and 7.51 h at a dose of 1 or 5 mg/kg Guanosine, respectively. ACF had no effect on the plasma disappearance of Guanosine following either i.v. bolus or i.m. administration of the combination mixture. Moreover, the ACF combination with Guanosine did not significantly alter the values of MRT, Vdss, and CLt of Guanosine. Guanosine exhibited linear pharmacokinetics over the dose range from 1 to 5 mg/kg for i.v. doses and 3 to 15 mg/kg for i.m. doses. The bioavailability of Guanosine after i.m. administration was 84% for 3 mg/kg dose and 88% for 15 mg/kg dose. ACF had no effects on biliary and urinary excretion of Guanosine after i.m. administration. The cumulative amount of Guanosine in urine after i.m. administration was about 5-fold larger than that in bile, indicating that Guanosine is mostly excreted into the urine. Guanosine was widely distributed in all tissues examined in this study, but was most highly concentrated in the kidney after i.m. administration, followed by slow excretion to bile or urine. ACF had no effect on the tissue distribution of Guanosine following i.m. administration. These characterizations of the pharmacokinetics of Guanosine after administration of the ACF/Guanosine combination will be useful in providing preclinical and clinical bases for the potential application of this combination to the treatment of cancer.

  • effects of Guanosine on the pharmacokinetics of acriflavine in rats following the administration of a 1 1 mixture of acriflavine and Guanosine a potential antitumor agent
    Archives of Pharmacal Research, 2007
    Co-Authors: Pung Sok Lee, Dae Hwan Shin, Sukgil Song, Dongcheul Moon, Jin Tae Hong, Kyoungmi Lee, Hwansoo Yoo, Youn Bok Chung
    Abstract:

    Preclinical studies are currently underway to examine the potential antitumor effects of a 1:1 mixture of acriflavine (ACF; CAS 8063-24-9) and Guanosine. Guanosine potentiates the anti-cancer activity of some compounds. However, the effects of Guanosine on the pharmacokinetics of ACF in mammals are unknown. Therefore, this study investigated the effects of Guanosine on the pharmacokinetics of ACF after administering a 1:1 mixture of ACF and Guanosine in rats. The rats were given either 10 mg/kg of the mixture or 5 mg/kg ACF via an intravenous bolus injection; or 30 mg/kg of the mixture or 15 mg/kg ACF intramuscularly. An HPLC-based method, which was validated in this laboratory, was used to analyze the levels of trypaflavine (TRF) and proflavine (PRF) in the plasma, bile, urine, and tissue homogenates. It was found that TRF and PRF were rapidly cleared from the blood and transferred to the tissues after the i.v. bolus or i.m. injection of the combination mixture. Both TRF and PRF were found to be most highly concentrated in the kidneys after the i.v. bolus or i.m. injection, followed by slow excretion to the bile or urine. Guanosine had no effect on the plasma disappearance of TRF or PRF after the i.v. bolus injection. However, Guanosine led to a prolongation of the plasma levels of PRF after the i.m. administration of the combination mixture, resulting in a 2 fold increase in the bioavailability (BA) of PRF. The concentrations of TRF and PRF in all the tissues examined were similar in the groups given the mixture and ACF. However, Guanosine led to a prolongation of the biliary and urinary excretions of both TRF and PRF after the i.v. bolus (1.25 fold) or i.m. (1.5-2.4 folds) injection. These prolonged effects of Guanosine on the plasma disappearance or urinary excretion of TRF and PRF might be one reason for the enhanced antitumor effects of ACF. However, more study will be needed to further examine this potential mechanism.

Annalisa Bellanca - One of the best experts on this subject based on the ideXlab platform.

  • preventive effects of Guanosine on intestinal inflammation in 2 4 dinitrobenzene sulfonic acid dnbs induced colitis in rats
    Inflammopharmacology, 2019
    Co-Authors: Maria Grazia Zizzo, Domenico Nuzzo, Marta Di Carlo, Gaetano Felice Caldara, Annalisa Bellanca, R Serio
    Abstract:

    Guanosine, a guanine-based purine, is an extracellular signaling molecule exerting anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. We aimed to investigate its protective effects on 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rat. Rats were divided into five groups and colitis was induced by intracolonic instillation of DNBS (15 mg/rat). Guanosine (4 or 8 mg/kg) was administered for 6 days i.p. starting the day of the colitis induction. Body weight loss, stool consistency, colon weight/length, histological analysis, myeloperoxidase activity (MPO) and pro-inflammatory cytokine levels were assessed. Immunoblotting of nuclear factor-κB (NF-κB) p65 protein levels and detection of oxidative and nitrosative stress markers were also performed. Guanosine, in a dose-dependent manner, significantly ameliorated the severity of DNBS-induced colitis, reducing body weight loss and diarrhea incidence, preventing the DNBS-induced macroscopic and microscopic damage to the colonic mucosa, and the MPO increase. Guanosine treatment also lowered interleukin-1β, interleukin-6, and tumor necrosis factor-α mRNA levels. Importantly, Guanosine in DNBS rats down-regulated the expression of NF-κB p65 and the levels of reactive oxygen species and nitrite. In conclusion, Guanosine exerts beneficial effects in DNBS-induced colitis in rats, through modulation of colonic inflammation, downregulating of NFκB-mediated signaling.

Gaetano Felice Caldara - One of the best experts on this subject based on the ideXlab platform.

  • preventive effects of Guanosine on intestinal inflammation in 2 4 dinitrobenzene sulfonic acid dnbs induced colitis in rats
    Inflammopharmacology, 2019
    Co-Authors: Maria Grazia Zizzo, Domenico Nuzzo, Marta Di Carlo, Gaetano Felice Caldara, Annalisa Bellanca, R Serio
    Abstract:

    Guanosine, a guanine-based purine, is an extracellular signaling molecule exerting anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. We aimed to investigate its protective effects on 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rat. Rats were divided into five groups and colitis was induced by intracolonic instillation of DNBS (15 mg/rat). Guanosine (4 or 8 mg/kg) was administered for 6 days i.p. starting the day of the colitis induction. Body weight loss, stool consistency, colon weight/length, histological analysis, myeloperoxidase activity (MPO) and pro-inflammatory cytokine levels were assessed. Immunoblotting of nuclear factor-κB (NF-κB) p65 protein levels and detection of oxidative and nitrosative stress markers were also performed. Guanosine, in a dose-dependent manner, significantly ameliorated the severity of DNBS-induced colitis, reducing body weight loss and diarrhea incidence, preventing the DNBS-induced macroscopic and microscopic damage to the colonic mucosa, and the MPO increase. Guanosine treatment also lowered interleukin-1β, interleukin-6, and tumor necrosis factor-α mRNA levels. Importantly, Guanosine in DNBS rats down-regulated the expression of NF-κB p65 and the levels of reactive oxygen species and nitrite. In conclusion, Guanosine exerts beneficial effects in DNBS-induced colitis in rats, through modulation of colonic inflammation, downregulating of NFκB-mediated signaling.