Effect of neutropenia on gastric mucosal integrity and mucosal nitric oxide synthesis in the rat

Tepperman, Barry L.; Vozzolo, Benito L.; Soper, B. D.

doi:10.1007/bf01297085

Cited by 27 publications

(8 citation statements)

References 22 publications

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“…To clarify the influence of neutrophils and pancreatic injury, we used a neutrophil depletion model. Rabbit anti-rat neutrophil serum [26,27], MTX [28][29][30] or vinblastin sulfate [31] have been used to deplete neutrophils. In our model, the intraperitoneal injections of MTX were used to produce neutrophil deple tion, and neutrophil infiltration into the pancreatic tissue was assessed by measuring tissue myeloperoxidase activi ty.…”

Section: Discussionmentioning

confidence: 99%

Role of Neutrophils in Cerulein-Induced Pancreatitis in Rats: Possible Involvement of Apoptosis

Fujimoto¹,

Hosotani²,

Doi³

et al. 1997

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We investigated the role of neutrophils and the involvement of apoptosis in cerulein-induced acute pancreatitis. Male Sprague-Dawley rats were divided into 2 groups. In the control group, acute pancreatitis was induced by subcutaneous injections of cerulein. In methotrexate-treated group, the rats received intraperitoneal injections of methotrexate to produce neutrophil depletion before the injections of cerulein. The rats were sacrificed at the indicated time points until 72 h after the first injection of cerulein. Neutrophil depletion ameliorated pancreatic edema and vacuole formation in acinar cells during the early stages of cerulein-induced acute pancreatitis. Electron microscopy, DNA gel electrophoresis and in situ nick end-labeling revealed the involvement of apoptosis in acinar cells in cerulein-induced acute pancreatitis. Furthermore, the number of apoptotic acinar cells in neutrophil-depleted rats showed an about 2-fold increase during the late stages when compared with those in the control rats. Our results suggest that neutrophil depletion in cerulein-induced pancreatitis leads to amelioration of pancreatic injury during the early stage, and enhancement of apoptosis by neutrophil depletion occurs during the late stage.

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Section: Discussionmentioning

confidence: 99%

Role of Neutrophils in Cerulein-Induced Pancreatitis in Rats: Possible Involvement of Apoptosis

Fujimoto¹,

Hosotani²,

Doi³

et al. 1997

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“…), followed by the local intra-arterial infusion of the NO donors. The dose of antineutrophil serum was derived from previous studies (Tepperman et al, 1993). The reduction in the number of circulating neutrophils was determined by differential staining of a blood sample taken from the abdominal aorta of pentobarbitone-anaesthetized rats, 4 h after antibody injection, using a modified Wright-Giesma stain (Diff-Quick; Baxter Corp., Fl., U.S.A.).…”

Section: Effects Of Paf-receptor Antagonists and Thromboxane Synthasementioning

confidence: 99%

Involvement of superoxide and xanthine oxidase in neutrophil‐independent rat gastric damage induced by NO donors

Lamarque

Whittle

1995

British J Pharmacology

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1 Nitric oxide (NO) and the superoxide anion can interact to form the cytotoxic moiety, peroxynitrite. The involvement and potential source of superoxide in the gastric mucosal damage induced by local infusion of NO donors, has now been investigated in the pentobarbitone-anaesthetized rat.2 Local intra-arterial infusion of the NO donor, sodium nitroprusside (40 ,g kg-' min-) for 10 min induced macroscopically apparent gastric mucosal injury. 3 This mucosal damage was dose-dependently reduced by prior administration of a systemically acting form of superoxide dismutase conjugated with polyethylene glycol (500-2000 iu kg-', i.v.).4 Likewise, the mucosal damage induced by nitroprusside was dose-dependently reduced by prior administration of the xanthine oxidase inhibitor, allopurinol (20-100 mg kg-, i.p. or 100 mg kg-, p.o.). 5 Pretreatment with allopurinol (100 mg kg-', i.p.) also reduced the mucosal injury induced by local intra-arterial infusion of the nitrosothiol, S-nitroso-N-acetyl-penicillamine (40 jg kg-' min-), but not that induced by local infusion of endothelin-1 (5 pmol kg-min-'), indicating specificity of action.6 Prior administration (4h) of rabbit anti-rat neutrophil serum (0.4 ml kg-, i.p.), which reduced circulating neutrophils by 90%, did not significantly protect against mucosal injury induced by nitroprusside.7 Intravenous administration of the platelet-activating factor receptor antagonists, WEB 2086 (1 mg kg-') or BN 52021 (10 mg kg-), or the thromboxane synthase inhibitor, OKY 15181 (25 mg kg-), did not modify mucosal damage induced by nitroprusside, showing lack of involvement of these neutrophilderived mediators. 8 These findings indicate the involvement of superoxide in the injurious actions of the NO donors, implicating a cytotoxic role of peroxynitrite. Xanthine oxidase, but not neutrophils, appears to be a source of the superoxide.

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“…Administration of an anti-neutrophil serum protects the intestinal mucosa against ischaemia-reperfusion and indomethacin-induced damage (Hernandez et al, 1987;Chmaisse et al, 1994) and reduces the susceptibility of the gastric mucosa to injury by ethanol (Kvietys et al, 1990;Tepperman et al, 1993), indomethacin (Wallace et al, 1990) or PAF (Etienne et al, 1988). The involvement of neutrophils in at least part of the intestinal vascular injury in the current acute model is suggested by the findings that the administration of an anti-neutrophil serum significantly inhibited the microvascular leakage.…”

Section: Discussionmentioning

confidence: 59%

Attenuation by nitrosothiol NO donors of acute intestinal microvascular dysfunction in the rat

László

Whittle

Moncada

1995

British J Pharmacology

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1 The effects of the nitric oxide (NO) donors, S-nitroso-glutathione (SNOG) and S-nitroso-N-acetylpenicillamine (SNAP), on the acute intestinal microvascular dysfunction induced by N'-nitro-L-arginine methyl ester (L-NAME) in combination with low doses of endotoxin were investigated in the anaesthetized rat. 2 Administration of L-NAME (5 mg kg', s.c.) concurrently with E. coli lipopolysaccharide (LPS, 3 mg kg-1, i.v.) provoked the leakage of radiolabelled albumin in the ileum and colon, as a measure of microvascular damage, determined 1 h after challenge.3 Intravenous infusion of SNOG or SNAP (1-lOpgkg-'min'1) dose-dependently attenuated the microvascular leakage induced by L-NAME and LPS.4 Infusion of the lowest doses of SNOG or SNAP (1 jig kg-' min', i.v.) that significantly reduced the albumin leakage, did not affect the increase in blood pressure in response to L-NAME in LPS-treated rats. Higher doses of SNOG or SNAP (5-I0lg kg-' min', i.v.) dose-dependently reduced this increase in blood pressure.5 In control studies, intravenous infusion of glutathione (10fig kg-' min-') or N-acetyl-penicillamine (I0 ig kg-l minm) had no effect on microvascular leakage in the ileum and colon induced by LPS and L-NAME.6 Pretreatment with rabbit anti-rat neutrophil serum (0.4 ml kg-', i.p., 4 h before challenge), which reduced the neutrophil count in peripheral arterial blood, also inhibited the microvascular leakage in the ileum and colon. 7 The protective effects of the nitrosothiol NO donors in this model may reflect, in part, modulation of neutrophil interactions within the microcirculation or actions on endothelial cell integrity, in addition to any local vasodilator action.

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Effect of neutropenia on gastric mucosal integrity and mucosal nitric oxide synthesis in the rat

Cited by 27 publications

References 22 publications

Role of Neutrophils in Cerulein-Induced Pancreatitis in Rats: Possible Involvement of Apoptosis

Role of Neutrophils in Cerulein-Induced Pancreatitis in Rats: Possible Involvement of Apoptosis

Involvement of superoxide and xanthine oxidase in neutrophil‐independent rat gastric damage induced by NO donors

Attenuation by nitrosothiol NO donors of acute intestinal microvascular dysfunction in the rat

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