We studied the effect of pentoxifylline on retinal lipid peroxidation and histopathologic changes due to ischemia/reperfusion (I/R). A total of 15 pigmented male guinea pigs were divided into 3 equal groups as control, sham and treatment groups. After application of high intraocular pressure for 90 min for the induction of retinal ischemia, 24-hour reperfusion was established in the sham and treatment groups. In the treatment and sham groups, either 45 mg/kg of pentoxifylline or saline was given 3 times at 8-hour intervals. Biochemical assay and histopathologic evaluation were performed on one randomly selected eye of each animal which was enucleated at the end of the reperfusion period, and retinal malondialdehyde (MDA) levels and thickness of the retinal tissue were determined for each group. The mean MDA level of the sham group was significantly higher versus the control and treatment groups (p < 0.001). When compared with the control group, the mean MDA level of the treatment group was slightly higher, but the difference was not statistically significant (p > 0.05). In comparison with the control group there was a significant increase in the thickness of the retina in the sham group (p < 0.0001), and no significant difference was found in the retinal thickness of the treatment group (p > 0.05). Pentoxifylline might have a preventive effect on the I/R injury of the retina.

Keywords:
Pentoxifylline, Retinal ischemia and reperfusion
1.
Parks DA, Granger DN, Bulkley GB, Shah AK: Soybean trypsin inhibitor attenuates ischemic injury to the feline small intestine. Gastroenterology 1985;82:9–15.
2.
Szabo ME, Droy-Lefaix MT, Doly M, Carre C, Braquet P: Modification of ischemia/reperfusion-induced ion shifts (Na+, K+, Ca2+ and Mg2+) by free radical scavengers in the rat retina. Ophthalmic Res 1993;25:1–9.
3.
Szabo ME, Droy-Lefaix MT, Doly M, Carre C, Braquet P: Ischemia and reperfusion induced histologic changes in the rat retina. Invest Ophthalmol Vis Sci 1991;32:1471–1478.
4.
Ventura ACS, Böhnke M: Pentoxifylline influences the autocrine function of organ cultured donor corneas and enhances endothelial cell survival. Br J Ophthalmol 2001;85:1110–1114.
5.
D’Hellencourt CL, Diaw L, Cornillet P, Guenounou M: Differential regulation of TNF alpha, IL-1 beta, IL-6, IL-8, TNF beta, and IL-10 by pentoxifylline. Int J Immunopharmacol 1996;18:739–748.
6.
Chaouat G, Assal Meliani A, Martal J, Raghupathy R, Elliot J, Mosmann T, Wegmann TG: IL-10 prevents naturally occurring fetal loss in the CBA × DBA/2 mating combination, and local defect in IL-10 production in this abortion-prone combination is corrected by in vivo injection of IFN-tau. J Immunol 1995;154:4261–4268.
7.
Zabel P, Schoenharting MM, Schade FU: Effects of pentoxifylline in endotoxinemia in human volunteers. Prog Clin Biol Res 1991;367:207–213.
8.
Arias-Diaz J, Vara E, Torres-Melero J, Garcia C, Hernandez J, Balibrea JL: Local production of oxygen free radicals and nitric oxide in rat diaphragm during sepsis: Effects of pentoxifylline and somatostatin. Eur J Surg 1997;163:619–625.
9.
Hughes WF: Quantitation of ischemic damage in the rat retina. Exp Eye Res 1991;53:573–582.
10.
Alagoz G, Celiker U, Ilhan N, Yekeler H, Demir T, Celiker H: L-Carnitine in experimental retinal ischemia-reperfusion injury. Ophthalmologica 2002;216:144–150.
11.
Ohkawa H, Ohishi N, Yagi K: Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351–358.
12.
Sonkin PL, Sinclair SH, Hatchell DL: The effect of pentoxifylline on retinal capillary blood flow velocity and whole blood viscosity. Am J Ophthalmol 1993;115:775–780.
13.
Sonkin PL, Kelly LW, Sinclair SH, Hatchell DL: Pentoxifylline increases retinal capillary blood flow velocity in patients with diabetes. Arch Ophthalmol 1993;111:1647–1652.
14.
Kamphuis J, Smits P, Thien T: Vascular effects of pentoxifylline in humans. J Cardiovasc Pharmacol 1994;26:648–654.
15.
Nelson JL, Alexander JW, Mao JX, Vohs T, Ogle CK: Effect of pentoxifylline on survival and intestinal cytokine messenger RNA transcription in a rat model of ongoing peritoneal sepsis. Crit Care Med 1999;27:13–19.
16.
Incandela L, Cesarone MR, Belcaro G, Steigerwalt R, De Sanctis MT, Nicolaides AN, Griffin M, Geroulakos G, Ramaswami G: Treatment of vascular retinal disease with pentoxifylline: A controlled, randomized trial. Angiology 2002;53:31–34.
17.
De Sanctis MT, Cesarone MR, Belcaro G, Incandela L, Steigerwalt R, Nicolaides AN, Griffin M, Geroulakos G: Treatment of retinal vein thrombosis with pentoxifylline: A controlled, randomized trial. Angiology 2002;53:35–38.
18.
Koo DJ, Yoo P, Cioffi WG, Bland KI, Chaudry IH, Wang P: Mechanism of beneficial effects of pentoxifylline during sepsis: Maintenance of adrenomedullin responsiveness and downregulation of proinflammatory cytokines. J Surg Res 2000;91:70–76.
19.
Bath PM, Bath FJ, Asplund K: Pentoxifylline and pentifylline for acute ischemic stroke. Cochrane Database Syst Rev 2000;2:CD000162.
20.
Ishizaka A, Wu ZH, Stephens KE, Harada H, Hogue RS, O’Hanley PT, Raffin TA: Attenuation of acute lung injury in septic guinea pigs by pentoxifylline. Am Rev Respir Dis 1988;138:376–384.
21.
Rieneck K, Diamant M, Haahr PM, Schonharting M, Bendtzen K: In vitro immunomodulatory effects of pentoxifylline. Immunol Lett 1993;37:131–138.
22.
Werns SW, Shea MJ, Lucchesi BR: Free radicals in ischemic myocardial injury. J Free Radic Biol Med 1985;1:103–110.
23.
Ghezzi P, Dinarello CA, Bianchi M, Rosandich ME, Repine JE, White CW: Hypoxia increases production of interleukine-1 and tumor necrosis factor by human mononuclear cells. Cytokine 1991;3:189–194.
24.
Balibrea JL, Arias-Diaz J, Garcia C, Vara E: Effect of pentoxifylline and somatostatin on tumor necrosis factor production by human pulmonary macrophages. Circ Shock 1994;43:51–56.
25.
Smedley LA, Tonessen MG, Sandhaus RA, Haslett C, Guthrie LA, Johnston RB, Henson PM, Worthen GS: Neutrophil-mediated injury to endothelial cells: Enhancement by endotoxin and essential role of neutrophil elastase. J Clin Invest 1986;77:1233–1243.
26.
Dauber IM, Lesnefsky EJ, Ashmore RC, Martel DM, Sheridan FM, Weil JV, Horwitz LD: Coronary vascular injury due to ischemia-reperfusion is reduced by pentoxifylline. J Pharmacol Exp Ther 1992;260:1250–1256.
27.
Ophir A, Berenshtein E, Kitrossky N, Averbukh E: Protection of the transiently ischemic cat retina by zinc-desferrioxamine. Invest Ophthalmol Vis Sci 1994;35:1212–1222.
28.
Cadenas E: Biochemistry of oxygen toxicity. Annu Rev Biochem 1989;58:79–110.
29.
Hayreh SS, Podhajksy P: Ocular neovascularisation with retinal vascular occlusion. Arch Ophthalmol 1982;100:1585–1589.
30.
Bessler H, Gilgal R, Djadetti M, Zahavi I: Effect of pentoxifylline on the phagocytic activity, cAMP levels and superoxide anion production by monocytes and polymorphonuclear cells. J Leukocyte Biol 1986;40:747–754.
31.
Tsai LY, Lee KT, Tsai SM, Lee SC, Yu HS: Changes of lipid peroxide levels in blood and liver tissue of patients with obstructive jaundice. Clin Chim Acta 1993;215:41–50.
32.
Faberowski N, Stefannsson E, Davidson RC: Local hypothermia protects the retina from ischemia. Invest Ophthalmol Vis Sci 1989;30:2309–2313.
33.
Briggs RT, Robinson JM, Arnovsky ML, Karnovsky MJ: Superoxide production by polymorphonuclear leukocytes. Histochemistry 1986;84:371–378.
34.
Weiss SJ, Peppin GJ: Collagenolytic metalloenzymes of the human neutrophil: Characteristics, regulation and potential function in vivo. Biochem Pharmacol 1986;35:3189–3197.
35.
Mandell GL: Cytokines, phagocytes and pentoxifylline. J Cardiovasc Pharmacol 1995;25(suppl 2):20–22.
36.
Hinder RA, Stein HJ: Oxygen derived free radicals. Arch Surg 1991;126:104–106.
© 2003 S. Karger AG, Basel
2003
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.