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Salvatore Cuzzocrea - One of the best experts on this subject based on the ideXlab platform.

  • dimethyl fumarate reduces inflammatory responses in experimental colitis
    Journal of Crohns & Colitis, 2016
    Co-Authors: Giovanna Casili, Salvatore Cuzzocrea, Marika Cordaro, Daniela Impellizzeri, Giuseppe Bruschetta, Irene Paterniti, Emanuela Esposito
    Abstract:

    Background and Aims: Fumaric acid esters have been proven to be effective for the systemic treatment of psoriasis and multiple sclerosis. We aimed to develop a new treatment for colitis. Methods: We investigated the effect of dimethylfumarate [DMF, 10-30-100mg/kg] on an experimental model of colitis induced by dinitrobenzene sulphuric acid [DNBS]. We also evaluated the therapeutic activity of 7 weeks’ treatment with DMF [30mg/kg] on 9-week-old IL-10KO mice that spontaneously develop a T helper-1 [Th1]-dependent chronic enterocolitis after birth, that is fully established at 8–10 weeks of age. The mechanism of this pharmacological potential of DMF [10 μM] was investigated in Colonic epithelial cell monolayers [Caco-2] exposed to H2O2. The barrier function was evaluated by the tight junction proteins. Results: The treatment with DMF significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. DMF [30 and 100mg/kg] also caused a substantial reduction in the degree of Colon Injury, in the rise in myeloperoxidase [MPO] activity, and in the increase in tumour necrosis factor [TNF]-α expression, as well as in the up-regulation of ICAM-1 caused by DNBS in the Colon. Molecular studies demonstrated that DMF impaired NF-κB signalling via reduced p65 nuclear translocalisation. DMF induced a stronger antioxidant response as evidenced by a higher expression of Mn-superoxide dismutase. Moreover, DMF protected human intestinal epithelial cells against H2O2-induced barrier dysfunction, restoring ZO-1 occludin expression, via the HO-1 pathway. Conclusions: DMF treatment reduces the degree of colitis caused by DNBS. We propose that DMF treatment may be useful in the treatment of inflammatory bowel disease.

  • effects of 3 aminobenzamide an inhibitor of poly adp ribose polymerase in a mouse model of acute pancreatitis induced by cerulein
    European Journal of Pharmacology, 2006
    Co-Authors: Emanuela Mazzon, Rosanna Di Paola, Tiziana Genovese, Carmelo Muia, Concetta Crisafulli, Giuseppe Malleo, Emanuela Esposito, Rosaria Meli, Edoardo Sessa, Salvatore Cuzzocrea
    Abstract:

    Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the Colon Injury associated with experimental colitis. The aim of the present study was to examine the effects of 3-aminobenzamide (3-AB), an inhibitor of PARP activity, in the development of acute pancreatitis caused by cerulein in mice. Intraperitoneal injection of cerulein in mice resulted in severe, acute pancreatitis characterized by oedema, neutrophil infiltration and necrosis and elevated serum levels of amylase and lipase. Infiltration of pancreatic and lung tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced expression of the intercellular adhesion molecule-1 (ICAM-1) and P-selectin. Immunohistochemical examination demonstrated a marked increase in the staining (immunoreactivity) for transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) in the pancreas of cerulein-treated mice in comparison to sham-treated mice. Acute pancreatitis in vehicle-treated mice was also associated with a significant mortality (40% survival at 5 days after cerulein administration). In contrast, (1) the degree of pancreatic inflammation and tissue Injury (histological score), (2) upregulation/formation of ICAM-1 and P-selectin, (4) neutrophils infiltration and (5) the expression of TGF-β and VEGF was markedly reduced in pancreatic tissue obtained from cerulein-treated mice which have been treated with 3-AB. These findings provide the evidence that PARP inhibition reduce the degree of pancreas Injury caused by acute pancreatitis induced by cerulein administration.

  • the cyclopentenone prostaglandin 15 deoxy δ12 14 pgj2 attenuates the development of Colon Injury caused by dinitrobenzene sulphonic acid in the rat
    British Journal of Pharmacology, 2003
    Co-Authors: Salvatore Cuzzocrea, Nicole S. Wayman, Emanuela Mazzon, Laura Dugo, Rosanna Di Paola, Ivana Serraino, Prabal K. Chatterjee, Angela Ianaro, Barbara Pisano, Massimo Di Rosa
    Abstract:

    Inflammatory bowel disease (IBD) is characterized by oxidative and nitrosative stress, leukocyte infiltration, and increased expression of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) in the Colon. Recent evidence also suggests that the cyclopentenone prostaglandin (PG) 15-deoxy-Δ12,14-PGJ2 (15d- PGJ2) functions as an early anti-inflammatory signal. The aim of the present paper is to investigate the effects of 15d-PGJ2 in rats subjected to experimental colitis. Colitis was induced in rats by intra-Colonic instillation of dinitrobenzene sulphonic acid (DNBS). 15d-PGJ2 was administered daily as intraperitoneal injection (20 or 40 μg kg−1). On day 4, animals were sacrificed and tissues were taken for histological and biochemical analysis. 15d-PGJ2 significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. 15d-PGJ2 also caused a substantial reduction of (i) the degree of Colonic Injury, (ii) the rise in myeloperoxidase (MPO) activity (mucosa), (iii) the increase in the tissue levels of malondialdehyde (MDA) and (iv) of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β). Furthermore, 15d-PGJ2 reduced the increase in immunohistochemical staining for (i) inducible nitric oxide synthase (iNOS), (ii) nitrotyrosine and (iii) poly (ADP-ribose) polymerase (PARP), as well as (iv) the increased expression of ICAM-1 caused by DNBS in the Colon. Electrophoresis mobility shift assay (EMSA) of inflamed Colon revealed that 15d- PGJ2 also caused a substantial reduction of the activation of nuclear factor-kappaB (NF-κB). Furthermore, 15d-PGJ2 stimulates the activation of heat shock protein 72 (hsp72) in the inflamed Colon, as assessed by Western blot analysis. In conclusion, 15d-PGJ2 reduces the development of experimental colitis. British Journal of Pharmacology (2003) 138, 678–688. doi:10.1038/sj.bjp.0705077

  • Calpain inhibitor I reduces Colon Injury caused by dinitrobenzene sulphonic acid in the rat.
    Gut, 2001
    Co-Authors: Salvatore Cuzzocrea, Emanuela Mazzon, Tommaso Centorrino, Antonio Ciccolo, Michelle C. Mcdonald, Achille P. Caputi, Helder Mota-filipe, Maria Luisa Terranova, Domenico Britti, C. Thiemermann
    Abstract:

    BACKGROUND AND AIMS—Inflammatory bowel disease is characterised by oxidative and nitrosative stress, leucocyte infiltration, upregulation of expression of intercellular adhesion molecule 1 (ICAM-1), and upregulation of P-selectin in the Colon. The aim of the present study was to examine the effects of calpain inhibitor I in rats subjected to experimental colitis. METHODS—Colitis was induced in rats by intraColonic instillation of dinitrobenzene sulphonic acid (DNBS). RESULTS—Rats experienced haemorrhagic diarrhoea and weight loss. Four days after administration of DNAB, the mucosa of the Colon exhibited large areas of necrosis. Neutrophil infiltration (determined by histology as well as by an increase in myeloperoxidase activity in the mucosa) was associated with upregulation of ICAM-1 and P-selectin as well as high tissue levels of malondialdehyde. Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) polymerase (PARP) showed intense staining in the inflamed Colon. Staining of sections of Colon obtained from DNBS treated rats with an anti-cyclooxygenase 2 antibody showed diffuse staining of the inflamed tissue. Furthermore, expression of inducible nitric oxide synthase was found mainly in macrophages located within the inflamed Colon of DNBS treated rats. Calpain inhibitor I (5 mg/kg daily intraperitoneally) significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. Calpain inhibitor I also caused a substantial reduction in (i) degree of Colon Injury, (ii) rise in myeloperoxidase activity (mucosa), (iii) increase in tissue levels of malondialdehyde, (iv) increase in staining (immunohistochemistry) for nitrotyrosine and PARP, as well as (v) upregulation of ICAM-1 and P-selectin caused by DNBS in the Colon. CONCLUSION—Calpain inhibitor I reduces the degree of colitis caused by DNBS. We propose that calpain inhibitor I may be useful in the treatment of inflammatory bowel disease. Keywords: calpain; calpain inhibitor I; cyclooxygenase; nitric oxide; inflammatory bowel disease; rat

  • tempol a membrane permeable radical scavenger reduces dinitrobenzene sulfonic acid induced colitis
    European Journal of Pharmacology, 2000
    Co-Authors: Salvatore Cuzzocrea, Emanuela Mazzon, Laura Dugo, Antonio Ciccolo, Michelle C. Mcdonald, Achille P. Caputi, Maria Luisa Terranova, Valeria Lepore, Maria Teresa Fonti, C. Thiemermann
    Abstract:

    Inflammatory bowel disease is characterized by oxidative and nitrosative stress, leukocyte infiltration, and up-regulation of intercellular adhesion molecule 1 (ICAM-1) expression in the Colon. The aim of the present study was to examine the effects of tempol, a membrane-permeable radical scavenger, in rats subjected to experimental colitis. Colitis was induced in rats by intraColonic instillation of dinitrobenzene sulfonic acid. Rats experienced bloody diarrhea and significant loss of body weight. At 4 days after the administration of dinitrobenzene sulfonic acid, the Colon Injury comprised of large areas of mucosal necrosis. Neutrophil infiltration (measured as increase in myeloperoxidase activity in the mucosa) was associated with up-regulation of ICAM-1 and expression of P-selectin and high levels of malondialdehyde (an indicator of lipid peroxidation). Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) synthetase showed an intense staining in the inflamed Colon. Treatment of rats with tempol (15 mg/kg daily i.p.) significantly reduced the appearance of diarrhea and the loss in body weight. This was associated with a remarkable amelioration of the disruption of the Colonic architecture as well as a significant reduction in the degree of both neutrophil infiltration and lipid peroxidation in the inflamed Colon. Tempol also reduced the appearance of nitrotyrosine and poly (ADP-ribose) synthetase immunoreactivity in the Colon as well as the up-regulation of ICAM-1 and P-selectin. The results of this study suggest that membrane-permeable radical scavengers, such as tempol, exert beneficial effects in experimental colitis and may, hence, be useful in the treatment of inflammatory bowel disease.

Hany H Arab - One of the best experts on this subject based on the ideXlab platform.

  • Telmisartan Attenuates Colon Inflammation, Oxidative Perturbations and Apoptosis in a Rat Model of Experimental Inflammatory Bowel Disease
    2016
    Co-Authors: Hany H Arab, Muhammad Y. Al-shorbagy, Dalaal M. Abdallah, Noha N. Nassar
    Abstract:

    Accumulating evidence has indicated the implication of angiotensin II in the pathogenesis of inflammatory bowel diseases (IBD) via its proinflammatory features. Telmisartan (TLM) is an angiotensin II receptor antagonist with marked anti-inflammatory and antioxidant actions that mediated its cardio-, reno- and hepatoprotective actions. However, its impact on IBD has not been previously explored. Thus, we aimed to investigate the potential alleviating effects of TLM in tri-nitrobenezene sulphonic acid (TNBS)-induced colitis in rats. Pretreatment with TLM (10 mg/kg p.o.) attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI), Colon weight/length ratio, macroscopic damage, histopathological findings and leukocyte migration. TLM suppressed the inflammatory response via attenuation of tumor necrosis factor-a (TNF-a), prostaglandin E2 (PGE2) and myeloperoxidase (MPO) activity as a marker of neutrophil infiltration besides restoration of interleukin-10 (IL-10). TLM also suppressed mRNA and protein expression of nuclear factor kappa B (NF-kB) p65 and mRNA of cyclo-oxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proinflammatory genes with concomitant upregulation of PPAR-c. The alleviation of TLM to Colon Injury was also associated with inhibition of oxidative stress as evidenced by suppression of lipid peroxides and nitric oxide (NO) besides boosting glutathione (GSH), total anti-oxidant capacity (TAC) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). With respect to apoptosis, TLM downregulated the increased mRNA, protein expression and activity of caspase-3. It als

  • camel s milk ameliorates tnbs induced colitis in rats via downregulation of inflammatory cytokines and oxidative stress
    Food and Chemical Toxicology, 2014
    Co-Authors: Hany H Arab, Samir A Salama, Hany A Omar, Elshaimaa A Arafa, Ibrahim A Maghrabi
    Abstract:

    Abstract Current treatment strategies for inflammatory bowel diseases (IBD) are associated with several adverse effects, and thus, the search for effective agents with minimal side effects merits attention. Camel’s milk (CM) is endowed with antioxidant/anti-inflammatory features and has been reported to protect against diabetes and hepatic Injury, however, its effects on IBD have not been previously explored. In the current study, we aimed to investigate the potential alleviating effects of CM against TNBS-induced colitis in rats. CM (10 ml/kg b.i.d. by oral gavage) effectively suppressed the severity of Colon Injury as evidenced by amelioration of macroscopic damage, Colon weight/length ratio, histopathological alterations, leukocyte influx and myeloperoxidase activity. Administration of CM mitigated the Colonic levels of TNF-α and IL-10 cytokines. The attenuation of CM to Colon Injury was also associated with suppression of oxidative stress via reduction of lipid peroxides and nitric oxide along with boosting the antioxidant defenses through restoration of Colon glutathione and total anti-oxidant capacity. In addition, caspases-3 activity, an apoptotic marker, was inhibited. Together, our study highlights evidences for the promising alleviating effects of CM in colitis. Thus, CM may be an interesting complementary approach for the management of IBD.

  • telmisartan attenuates Colon inflammation oxidative perturbations and apoptosis in a rat model of experimental inflammatory bowel disease
    PLOS ONE, 2014
    Co-Authors: Hany H Arab, Dalaal M. Abdallah, Muhammad Y Alshorbagy, Noha N. Nassar
    Abstract:

    Accumulating evidence has indicated the implication of angiotensin II in the pathogenesis of inflammatory bowel diseases (IBD) via its proinflammatory features. Telmisartan (TLM) is an angiotensin II receptor antagonist with marked anti-inflammatory and antioxidant actions that mediated its cardio-, reno- and hepatoprotective actions. However, its impact on IBD has not been previously explored. Thus, we aimed to investigate the potential alleviating effects of TLM in tri-nitrobenezene sulphonic acid (TNBS)-induced colitis in rats. Pretreatment with TLM (10 mg/kg p.o.) attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI), Colon weight/length ratio, macroscopic damage, histopathological findings and leukocyte migration. TLM suppressed the inflammatory response via attenuation of tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2) and myeloperoxidase (MPO) activity as a marker of neutrophil infiltration besides restoration of interleukin-10 (IL-10). TLM also suppressed mRNA and protein expression of nuclear factor kappa B (NF-κB) p65 and mRNA of cyclo-oxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proinflammatory genes with concomitant upregulation of PPAR-γ. The alleviation of TLM to Colon Injury was also associated with inhibition of oxidative stress as evidenced by suppression of lipid peroxides and nitric oxide (NO) besides boosting glutathione (GSH), total anti-oxidant capacity (TAC) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). With respect to apoptosis, TLM downregulated the increased mRNA, protein expression and activity of caspase-3. It also suppressed the elevation of cytochrome c and Bax mRNA besides the upregulation of Bcl-2. Together, these findings highlight evidences for the beneficial effects of TLM in IBD which are mediated through modulation of Colonic inflammation, oxidative stress and apoptosis.

C. Thiemermann - One of the best experts on this subject based on the ideXlab platform.

  • Calpain inhibitor I reduces Colon Injury caused by dinitrobenzene sulphonic acid in the rat.
    Gut, 2001
    Co-Authors: Salvatore Cuzzocrea, Emanuela Mazzon, Tommaso Centorrino, Antonio Ciccolo, Michelle C. Mcdonald, Achille P. Caputi, Helder Mota-filipe, Maria Luisa Terranova, Domenico Britti, C. Thiemermann
    Abstract:

    BACKGROUND AND AIMS—Inflammatory bowel disease is characterised by oxidative and nitrosative stress, leucocyte infiltration, upregulation of expression of intercellular adhesion molecule 1 (ICAM-1), and upregulation of P-selectin in the Colon. The aim of the present study was to examine the effects of calpain inhibitor I in rats subjected to experimental colitis. METHODS—Colitis was induced in rats by intraColonic instillation of dinitrobenzene sulphonic acid (DNBS). RESULTS—Rats experienced haemorrhagic diarrhoea and weight loss. Four days after administration of DNAB, the mucosa of the Colon exhibited large areas of necrosis. Neutrophil infiltration (determined by histology as well as by an increase in myeloperoxidase activity in the mucosa) was associated with upregulation of ICAM-1 and P-selectin as well as high tissue levels of malondialdehyde. Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) polymerase (PARP) showed intense staining in the inflamed Colon. Staining of sections of Colon obtained from DNBS treated rats with an anti-cyclooxygenase 2 antibody showed diffuse staining of the inflamed tissue. Furthermore, expression of inducible nitric oxide synthase was found mainly in macrophages located within the inflamed Colon of DNBS treated rats. Calpain inhibitor I (5 mg/kg daily intraperitoneally) significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. Calpain inhibitor I also caused a substantial reduction in (i) degree of Colon Injury, (ii) rise in myeloperoxidase activity (mucosa), (iii) increase in tissue levels of malondialdehyde, (iv) increase in staining (immunohistochemistry) for nitrotyrosine and PARP, as well as (v) upregulation of ICAM-1 and P-selectin caused by DNBS in the Colon. CONCLUSION—Calpain inhibitor I reduces the degree of colitis caused by DNBS. We propose that calpain inhibitor I may be useful in the treatment of inflammatory bowel disease. Keywords: calpain; calpain inhibitor I; cyclooxygenase; nitric oxide; inflammatory bowel disease; rat

  • tempol a membrane permeable radical scavenger reduces dinitrobenzene sulfonic acid induced colitis
    European Journal of Pharmacology, 2000
    Co-Authors: Salvatore Cuzzocrea, Emanuela Mazzon, Laura Dugo, Antonio Ciccolo, Michelle C. Mcdonald, Achille P. Caputi, Maria Luisa Terranova, Valeria Lepore, Maria Teresa Fonti, C. Thiemermann
    Abstract:

    Inflammatory bowel disease is characterized by oxidative and nitrosative stress, leukocyte infiltration, and up-regulation of intercellular adhesion molecule 1 (ICAM-1) expression in the Colon. The aim of the present study was to examine the effects of tempol, a membrane-permeable radical scavenger, in rats subjected to experimental colitis. Colitis was induced in rats by intraColonic instillation of dinitrobenzene sulfonic acid. Rats experienced bloody diarrhea and significant loss of body weight. At 4 days after the administration of dinitrobenzene sulfonic acid, the Colon Injury comprised of large areas of mucosal necrosis. Neutrophil infiltration (measured as increase in myeloperoxidase activity in the mucosa) was associated with up-regulation of ICAM-1 and expression of P-selectin and high levels of malondialdehyde (an indicator of lipid peroxidation). Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) synthetase showed an intense staining in the inflamed Colon. Treatment of rats with tempol (15 mg/kg daily i.p.) significantly reduced the appearance of diarrhea and the loss in body weight. This was associated with a remarkable amelioration of the disruption of the Colonic architecture as well as a significant reduction in the degree of both neutrophil infiltration and lipid peroxidation in the inflamed Colon. Tempol also reduced the appearance of nitrotyrosine and poly (ADP-ribose) synthetase immunoreactivity in the Colon as well as the up-regulation of ICAM-1 and P-selectin. The results of this study suggest that membrane-permeable radical scavengers, such as tempol, exert beneficial effects in experimental colitis and may, hence, be useful in the treatment of inflammatory bowel disease.

Emanuela Mazzon - One of the best experts on this subject based on the ideXlab platform.

  • effects of 3 aminobenzamide an inhibitor of poly adp ribose polymerase in a mouse model of acute pancreatitis induced by cerulein
    European Journal of Pharmacology, 2006
    Co-Authors: Emanuela Mazzon, Rosanna Di Paola, Tiziana Genovese, Carmelo Muia, Concetta Crisafulli, Giuseppe Malleo, Emanuela Esposito, Rosaria Meli, Edoardo Sessa, Salvatore Cuzzocrea
    Abstract:

    Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the Colon Injury associated with experimental colitis. The aim of the present study was to examine the effects of 3-aminobenzamide (3-AB), an inhibitor of PARP activity, in the development of acute pancreatitis caused by cerulein in mice. Intraperitoneal injection of cerulein in mice resulted in severe, acute pancreatitis characterized by oedema, neutrophil infiltration and necrosis and elevated serum levels of amylase and lipase. Infiltration of pancreatic and lung tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced expression of the intercellular adhesion molecule-1 (ICAM-1) and P-selectin. Immunohistochemical examination demonstrated a marked increase in the staining (immunoreactivity) for transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) in the pancreas of cerulein-treated mice in comparison to sham-treated mice. Acute pancreatitis in vehicle-treated mice was also associated with a significant mortality (40% survival at 5 days after cerulein administration). In contrast, (1) the degree of pancreatic inflammation and tissue Injury (histological score), (2) upregulation/formation of ICAM-1 and P-selectin, (4) neutrophils infiltration and (5) the expression of TGF-β and VEGF was markedly reduced in pancreatic tissue obtained from cerulein-treated mice which have been treated with 3-AB. These findings provide the evidence that PARP inhibition reduce the degree of pancreas Injury caused by acute pancreatitis induced by cerulein administration.

  • the cyclopentenone prostaglandin 15 deoxy δ12 14 pgj2 attenuates the development of Colon Injury caused by dinitrobenzene sulphonic acid in the rat
    British Journal of Pharmacology, 2003
    Co-Authors: Salvatore Cuzzocrea, Nicole S. Wayman, Emanuela Mazzon, Laura Dugo, Rosanna Di Paola, Ivana Serraino, Prabal K. Chatterjee, Angela Ianaro, Barbara Pisano, Massimo Di Rosa
    Abstract:

    Inflammatory bowel disease (IBD) is characterized by oxidative and nitrosative stress, leukocyte infiltration, and increased expression of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) in the Colon. Recent evidence also suggests that the cyclopentenone prostaglandin (PG) 15-deoxy-Δ12,14-PGJ2 (15d- PGJ2) functions as an early anti-inflammatory signal. The aim of the present paper is to investigate the effects of 15d-PGJ2 in rats subjected to experimental colitis. Colitis was induced in rats by intra-Colonic instillation of dinitrobenzene sulphonic acid (DNBS). 15d-PGJ2 was administered daily as intraperitoneal injection (20 or 40 μg kg−1). On day 4, animals were sacrificed and tissues were taken for histological and biochemical analysis. 15d-PGJ2 significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. 15d-PGJ2 also caused a substantial reduction of (i) the degree of Colonic Injury, (ii) the rise in myeloperoxidase (MPO) activity (mucosa), (iii) the increase in the tissue levels of malondialdehyde (MDA) and (iv) of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β). Furthermore, 15d-PGJ2 reduced the increase in immunohistochemical staining for (i) inducible nitric oxide synthase (iNOS), (ii) nitrotyrosine and (iii) poly (ADP-ribose) polymerase (PARP), as well as (iv) the increased expression of ICAM-1 caused by DNBS in the Colon. Electrophoresis mobility shift assay (EMSA) of inflamed Colon revealed that 15d- PGJ2 also caused a substantial reduction of the activation of nuclear factor-kappaB (NF-κB). Furthermore, 15d-PGJ2 stimulates the activation of heat shock protein 72 (hsp72) in the inflamed Colon, as assessed by Western blot analysis. In conclusion, 15d-PGJ2 reduces the development of experimental colitis. British Journal of Pharmacology (2003) 138, 678–688. doi:10.1038/sj.bjp.0705077

  • Calpain inhibitor I reduces Colon Injury caused by dinitrobenzene sulphonic acid in the rat.
    Gut, 2001
    Co-Authors: Salvatore Cuzzocrea, Emanuela Mazzon, Tommaso Centorrino, Antonio Ciccolo, Michelle C. Mcdonald, Achille P. Caputi, Helder Mota-filipe, Maria Luisa Terranova, Domenico Britti, C. Thiemermann
    Abstract:

    BACKGROUND AND AIMS—Inflammatory bowel disease is characterised by oxidative and nitrosative stress, leucocyte infiltration, upregulation of expression of intercellular adhesion molecule 1 (ICAM-1), and upregulation of P-selectin in the Colon. The aim of the present study was to examine the effects of calpain inhibitor I in rats subjected to experimental colitis. METHODS—Colitis was induced in rats by intraColonic instillation of dinitrobenzene sulphonic acid (DNBS). RESULTS—Rats experienced haemorrhagic diarrhoea and weight loss. Four days after administration of DNAB, the mucosa of the Colon exhibited large areas of necrosis. Neutrophil infiltration (determined by histology as well as by an increase in myeloperoxidase activity in the mucosa) was associated with upregulation of ICAM-1 and P-selectin as well as high tissue levels of malondialdehyde. Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) polymerase (PARP) showed intense staining in the inflamed Colon. Staining of sections of Colon obtained from DNBS treated rats with an anti-cyclooxygenase 2 antibody showed diffuse staining of the inflamed tissue. Furthermore, expression of inducible nitric oxide synthase was found mainly in macrophages located within the inflamed Colon of DNBS treated rats. Calpain inhibitor I (5 mg/kg daily intraperitoneally) significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. Calpain inhibitor I also caused a substantial reduction in (i) degree of Colon Injury, (ii) rise in myeloperoxidase activity (mucosa), (iii) increase in tissue levels of malondialdehyde, (iv) increase in staining (immunohistochemistry) for nitrotyrosine and PARP, as well as (v) upregulation of ICAM-1 and P-selectin caused by DNBS in the Colon. CONCLUSION—Calpain inhibitor I reduces the degree of colitis caused by DNBS. We propose that calpain inhibitor I may be useful in the treatment of inflammatory bowel disease. Keywords: calpain; calpain inhibitor I; cyclooxygenase; nitric oxide; inflammatory bowel disease; rat

  • tempol a membrane permeable radical scavenger reduces dinitrobenzene sulfonic acid induced colitis
    European Journal of Pharmacology, 2000
    Co-Authors: Salvatore Cuzzocrea, Emanuela Mazzon, Laura Dugo, Antonio Ciccolo, Michelle C. Mcdonald, Achille P. Caputi, Maria Luisa Terranova, Valeria Lepore, Maria Teresa Fonti, C. Thiemermann
    Abstract:

    Inflammatory bowel disease is characterized by oxidative and nitrosative stress, leukocyte infiltration, and up-regulation of intercellular adhesion molecule 1 (ICAM-1) expression in the Colon. The aim of the present study was to examine the effects of tempol, a membrane-permeable radical scavenger, in rats subjected to experimental colitis. Colitis was induced in rats by intraColonic instillation of dinitrobenzene sulfonic acid. Rats experienced bloody diarrhea and significant loss of body weight. At 4 days after the administration of dinitrobenzene sulfonic acid, the Colon Injury comprised of large areas of mucosal necrosis. Neutrophil infiltration (measured as increase in myeloperoxidase activity in the mucosa) was associated with up-regulation of ICAM-1 and expression of P-selectin and high levels of malondialdehyde (an indicator of lipid peroxidation). Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) synthetase showed an intense staining in the inflamed Colon. Treatment of rats with tempol (15 mg/kg daily i.p.) significantly reduced the appearance of diarrhea and the loss in body weight. This was associated with a remarkable amelioration of the disruption of the Colonic architecture as well as a significant reduction in the degree of both neutrophil infiltration and lipid peroxidation in the inflamed Colon. Tempol also reduced the appearance of nitrotyrosine and poly (ADP-ribose) synthetase immunoreactivity in the Colon as well as the up-regulation of ICAM-1 and P-selectin. The results of this study suggest that membrane-permeable radical scavengers, such as tempol, exert beneficial effects in experimental colitis and may, hence, be useful in the treatment of inflammatory bowel disease.

William C Parks - One of the best experts on this subject based on the ideXlab platform.

  • Matrix metalloproteinase-7 (matrilysin) controls neutrophil egress by generating chemokine gradients
    2013
    Co-Authors: Mei Swee, John K Mcguire, Carole L Wilson, Ying Wang, William C Parks
    Abstract:

    (MMP7)] is induced by mucosal Injury of many tissues. To assess function of this proteinase, we subjected wild-type and Mmp7 �/ � mice to acute Colon Injury. When matrilysin expression was increasing, 73 % of wild-type mice died, whereas only 32 % of Mmp7 �/ � mice succumbed. Although re-epithelialization was delayed in Mmp7 �/ � mice, overall Injury did not differ markedly between genotypes. We hypothesized that differences in acute inflammation caused increased mortality in wild-type mice. Indeed, whereas overall neutrophil influx into tissue was similar in wild-type and Mmp7 �/ � mice, their location and extent of migration differed between genotypes. Neutrophils were dispersed throughout the mucosa and within the lumen of wild-type mice, but these leukocytes were largely confined to the submucosa in Mmp7 �/ � mice. The levels of neutrophil chemokines, keratinocyte-derived chemokine and MIP-2, increased in the Colon tissue of both genotypes, but these factors were detected only in lumenal lavages of wild-type mice. Our findings indicate that matrilysin mediates beneficial and deleterious effects in response to Injury. On one hand, it promotes re-epithelialization, but it also controls the transepithelial influx of neutrophils, which if excessive, can lead t

  • matrix metalloproteinase 7 matrilysin controls neutrophil egress by generating chemokine gradients
    Journal of Leukocyte Biology, 2008
    Co-Authors: Mei Swee, John K Mcguire, Carole L Wilson, Ying Wang, William C Parks
    Abstract:

    Matrilysin [matrix metalloproteinase 7 (MMP7)] is induced by mucosal Injury of many tissues. To assess function of this proteinase, we subjected wild-type and Mmp7(-/-) mice to acute Colon Injury. When matrilysin expression was increasing, 73% of wild-type mice died, whereas only 32% of Mmp7(-/-) mice succumbed. Although re-epithelialization was delayed in Mmp7(-/-) mice, overall Injury did not differ markedly between genotypes. We hypothesized that differences in acute inflammation caused increased mortality in wild-type mice. Indeed, whereas overall neutrophil influx into tissue was similar in wild-type and Mmp7(-/-) mice, their location and extent of migration differed between genotypes. Neutrophils were dispersed throughout the mucosa and within the lumen of wild-type mice, but these leukocytes were largely confined to the submucosa in Mmp7(-/-) mice. The levels of neutrophil chemokines, keratinocyte-derived chemokine and MIP-2, increased in the Colon tissue of both genotypes, but these factors were detected only in lumenal lavages of wild-type mice. Our findings indicate that matrilysin mediates beneficial and deleterious effects in response to Injury. On one hand, it promotes re-epithelialization, but it also controls the transepithelial influx of neutrophils, which if excessive, can lead to tissue damage.