Heparins as essential antioxidants

Grant, David M.; Long, William F.; Mackintosh, G. M.; Williamson, Frank B.

doi:10.1007/bf01987642

Cited by 5 publications

(5 citation statements)

References 9 publications

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“…Although heparin is able to block voltage-gated Ca# + channels [48,49], we have previously ruled this out as a means of suppressing c-fos induction [13], and in the present study further discount this possibility by using an ionophore to circumvent channel-dependent entry. Heparin chains can act as scavengers of oxygen radicals [50,51], and could conceivably alter radical-dependent signal-transduction pathways [52] by scavenging diffusible radicals at the cell surface. However, catalase and superoxide dismutase were without effect on c-fos induction by ionomycin (T. Miralem and D. M. Templeton, unpublished work).…”

Section: Discussionmentioning

confidence: 99%

Heparin inhibits Ca2+/calmodulin-dependent kinase II activation and c-fos induction in mesangial cells

Miralem

Templeton

1998

Biochemical Journal

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Like vascular smooth-muscle cells, rat mesangial cells (RMCs) display an anti-mitogenic response to heparin. In particular, heparin partially suppresses the ability of quiescent RMCs to enter the cell cycle and induce c-fos expression. When the mitogenic stimulus is serum, phorbol ester or platelet-derived growth factor, this response appears to result from the ability of heparin to suppress activation of the extracellular-signal-regulated kinase family of mitogen-activated protein kinases. However, we have also shown that heparin suppresses c-fos expression in response to ionophores such as ionomycin, an event independent of mitogen-activated protein kinase [Miralem, Wang, Whiteside and Templeton (1996) J. Biol. Chem. 271, 17100-17106]. Here we identify this second heparin-sensitive pathway as involving Ca2+/calmodulin-dependent kinase (CaMK) II. Ionomycin (100 nM) caused a transient rise in intracellular Ca2+ concentration ([Ca2+]i) in quiescent RMCs to 386+/-55 nM, with an increase in CaMK II activity that peaked 30 s later. The accumulation of c-fos mRNA that ensued 30 min later was prevented when the increase in [Ca2+]i was prevented with the intracellular Ca2+ chelator, 1,2-bis-(2-aminophenyoxy)ethane-N,N,N',N'-tetra-acetic acid. The broad-specificity CaMK inhibitor, KT 5926, inhibited ionomycin-dependent c-fos induction at a concentration at which it was without effect on induction by serum or phorbol ester. The CaMK II-specific inhibitor, KN-93, likewise inhibited c-fos induction by ionomycin, but not by serum or phorbol ester. ML-7, an inhibitor of the CaMK-related myosin light-chain kinase (MLCK), was without effect. Heparin (1 microg/ml) suppressed ionomycin-dependent c-fos induction. It was without effect on [Ca2+]i, but inhibited the development of autonomous CaMK II activity. However, when heparin was added to the CaMK II assay solution in vitro, it was without effect on autonomous activity. Furthermore, heparin did not prevent full activation of CaMK II by the Ca2+-calmodulin complex in vitro. Heparin did not affect myosin light-chain phosphorylation or RMC contraction, processes mediated by MLCK. We conclude that ionomycin induces c-fos in RMCs through the CaMK II pathway, and that heparin prevents CaMK II activation by an indirect process mediated by other cell components. Heparin does not affect activation of the closely related CaMK, MLCK.

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Section: Discussionmentioning

confidence: 99%

Heparin inhibits Ca2+/calmodulin-dependent kinase II activation and c-fos induction in mesangial cells

Miralem

Templeton

1998

Biochemical Journal

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“…It has recently been shown that scavenging of H 2 O 2 , an inhibitor of phosphatases (59), suppressed platelet-derived growth factor signaling (60), possibly by decreasing the level of phosphorylated signaling intermediates. Heparin chains can act as scavengers of oxygen radicals (61,62) and might conceivably alter signal transduction pathways by scavenging diffusible oxygen radicals at the cell surface. However, heparin failed to affect endothelin-induced contraction in our cultures, an event dependent on Ca 2ϩ release and myosin light chain kinase activation, 2 arguing against such a general effect.…”

Section: Discussionmentioning

confidence: 99%

Heparin Inhibits Mitogen-activated Protein Kinase-dependent and -independent c- Induction in Mesangial Cells

Miralem

Wang

Whiteside

et al. 1996

Journal of Biological Chemistry

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Heparin also inhibited the serum-stimulated entry of extracellular Ca 2؉ to the same extent as verapamil, consistent with the ability of verapamil to block L-type Ca 2؉ channels and the known presence of these channels in mesangial cells. However, this effect does not appear to be related to heparin's ability to inhibit induction of c-fos. First, verapamil had no effect on induction of c-fos by serum. Second, heparin had no effect on changes in [Ca 2؉ ] i achieved by ionophores. We conclude that heparin suppresses induction of c-fos in mesangial cells by blocking at least two different points in signal transduction cascades, one upstream of MAPK and the other independent of MAPK, but dependent on intracellular Ca 2؉

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“…It was observed that GSH-Px activity was significantly reduced in the sham group compared to PTX and heparin groups. It has been reported here that GSX-Px increase in heparin and PTX groups shows that heparin can act as synergistic endogenous antioxidants with other free radical inhibitors [25,41]. Pentoxifylline is a powerful free radical scavenger and has a reducing effect on superoxide release and neutrophil degranulation [29].…”

Section: Discussionmentioning

confidence: 78%

“…It is observed that antioxidant application reduced the severity and degree of adhesions after intestinal ischemia in rats [1]. Thus, it has been reported that heparin can act as a synergistic endogenous antioxidant with other free radical inhibitors [25,41]. PTX is a potent free radical scavenger and has a reducing effect on superoxide release and neutrophil degranulation [29].…”

Section: Discussionmentioning

confidence: 99%

Surgery-Induced Changes in Erythrocyte and Plasma Lipid Peroxidation, Enzymatic and Non-Enzymatic Antioxidants of Female Rats: Protective Role of Heparin and Pentoxifylline

Şimşek

Durmuş

Yıldız

et al. 2018

Acta Scientiae. Vet.

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Background: Intra abdominal adhesions are a complication that occurs after many abdominal surgical procedures, especially gynecological operations. These complications occur by irritating the peritoneum due to such circumstances as infection or surgical trauma, and are considered a pathological part of the healing process of peritoneal injury. It manifests itself with symptoms such as pain, intestinal or urethral obstruction and abdominal abscesses. Oxidative stress due to adhesions plays an important role on adhesion formation. In addition to many researches done at the point of prevention of adhesion and decreasing stress parameters, in this study, it was planned to determine the effect of Heparin (H) and Pentoxifylline (PTX) on malondialdehyde (MDA) and some antioxidant values.Materials, Methods & Results: This study was performed on rats and thirty-seven female Sprague-Dawley rats were randomized into four groups. The first group was sham (Sh) group (n = 7) and laparotomy was performed and 2 mL of 0.9 % NaCl was applied. For all other rats (n = 30) the small intestine was withdrawn and the uterus was uncovered and the anti mesenteric surfaces of the left uterine horn and left abdominal wall were superficially tilted until slight bleeding was seen. Lesion areas have been covered. Two mL 0.9 % NaCl to control (C) group (n = 10), 500 IU heparin to group H, and 25 mg / kg Pentoxifylline to group PTX (n = 10) have been given and then the abdominal incision was closed. The adhesion score of group Sh was found to be more important than C and PTX groups (P < 0.05). The adhesion score of group C was determined to be more significant than group H (P < 0.05). In group Sh, erythrocyte reduced glutathione (GSH) levels were found to be more significant (P < 0.01) than C, H and PTX groups whereas it was found that group C was more significant than group H (P < 0.01). In group Sh, glutathione peroxidase (GSH-Px) activity was found to be more significant (P < 0.05) than H and PTX groups, while MDA level was found to be lower and more significant (P < 0.01) than group C. In addition, group C was found to be higher and more significant (P < 0.01) than group H. Plasma vitamin E levels in Sh, H and PTX groups were found to be higher and more significant (P < 0.01) than group C. It is also observed that MDA levels in group C are higher and more significant (P < 0.01) than all groups. Nitric oxide (NO) level in Sh group was found to be lower and more significant (P < 0.05) than the other groups whereas it is determined that NO level in H group is higher and more significant (P < 0.05) than group C. Activites of erythrocyte catalase (CAT) and superoxide dismutase (SOD), the levels of plasma vitamin A and β-carotene were not important in all groups.Discussion: Intra abdominal adhesions that occur due to operations performed in the abdominal region still remain as a major problem. This adhesion brings certain problems with itself. Various applications have been made to reduce these problems. In this study, it was observed that inhibition of heparin and pentoxifylline adhesions contributed to the reduction of MDA levels and the reduction of oxidative damage due to the increase in levels of Vitamin E, GSH, GSH-Px and NO levels. In conclusion, it is suggested that heparin and pentoxifylline should be used to prevent adhesions due to abdominal operations and to reduce oxidative damage.

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Heparins as essential antioxidants

Abstract: Abstract. Chronically inflamed tissues contain significant concentrations of oxygen radicals, possibly generated by transition metal species such as Fe(II) and Cu

Cited by 5 publications

References 9 publications

Heparin inhibits Ca2+/calmodulin-dependent kinase II activation and c-fos induction in mesangial cells

Heparin inhibits Ca2+/calmodulin-dependent kinase II activation and c-fos induction in mesangial cells

Heparin Inhibits Mitogen-activated Protein Kinase-dependent and -independent c- Induction in Mesangial Cells

Surgery-Induced Changes in Erythrocyte and Plasma Lipid Peroxidation, Enzymatic and Non-Enzymatic Antioxidants of Female Rats: Protective Role of Heparin and Pentoxifylline

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