Ophthalmic Research

Original Paper

Maintaining the Redox-Balance Intact: Gosha-Jinki-Gan but Not Insulin Activates Retinal Soluble Guanylate Cyclase in Diabetic Rats

Cameron-Schaefer S.a-c · Kondo K.b · Ishige A.a · Tsuyama S.d · Uchida K.e · Hanawa T.c · Suematsu M.b · Watanabe K.a

Author affiliations

Departments of aOriental Medicine and bBiochemistry and Integrative Medical Biology, Keio University School of Medicine, and cOriental Medicine Research Center of the Kitasato Institute, Tokyo, dDepartment of Veterinary Science, Osaka Prefecture University, Osaka, eLaboratory of Food and Biodynamics, Nagoya University Graduate School of Bioagricultural Sciences, Nagoya, Japan

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Ophthalmic Res 2006;38:95–104

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: June 09, 2005
Accepted: August 29, 2005
Published online: March 01, 2006
Issue release date: February 2006

Number of Print Pages: 10
Number of Figures: 5
Number of Tables: 0

ISSN: 0030-3747 (Print)
eISSN: 1423-0259 (Online)

For additional information: https://www.karger.com/ORE

Abstract

Strategies to prevent hyperglycemia-induced cytotoxic reactive oxygen species in the retina include the prevention of free radical production, activation of radical-scavenging capacities and inhibition of aldose reductase. This study examined the effect of the standardized Japanese herbal extract product gosha-jinki-gan (GJG) in comparison to insulin treatment in the rat retina. Diabetes was induced in male Wistar rats by single injection of streptozotocin (50 mg/kg i.p.). At 6 and 12 weeks, eyecups were removed for immunohistochemistry. At 12 weeks, lipid peroxidation (tested with the antiacrolein antibody, Ab5F6) was enhanced significantly in the untreated diabetic group. This effect was absent in both treatment groups, notably in the outer retina. A similar result was obtained for nitrotyrosine overproduction. As an early treatment effect, GJG – but not insulin – enhanced soluble guanylate cyclase (sGC) activation (using the function-sensing antibody, MoAb 3221). GJG not only reduces nitroxidative stress and lipid peroxidation in the retina, it also ameliorates glucose metabolism within the cells. We propose that the high glucose turnover in the insulin-treated model disturbs the intracellular redox equilibrium, one result of which might be the impaired sGC activation.

© 2006 S. Karger AG, Basel




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References

  1. UK Prospective Diabetes Study (UKPDS) Group: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837–853.
  2. DCCT Research Group: Diabetes Control and Complications Trial (DCCT) – Update. Diabetes Care 1990;13:427–433.
  3. DCCT Research Group: The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes 1995;44:968–983.
  4. Kumagai AK: Glucose transport in brain and retina: implications in the management and complications of diabetes. Diabetes Metab Res Rev 1999;15:261–273.
  5. Vilchis C, Salceda R: Characterization of [2-3H]deoxy-D-glucose uptake in retina and retinal pigment epithelium of normal and diabetic rats. Neurochem Int 1996;28:213–219.
  6. Rosenzweig SA, Zetterstroem C, Benjamin A: Identification of retinal insulin receptors using site-specific antibodies to a carboxyl-terminal peptide of the human insulin receptor α-subunit. J Biol Chem 1990;265:18030–18034.
  7. Zetterstroem C, Benjamin A, Rosenzweig SA: Differential expression of retinal insulin receptors in STZ-induced diabetic rats. Diabetes 1992;41:818–825.
  8. Reichenbach A, Stolzenburg JU, Eberhardt W, Chao TI, Dettmer D, Hertz L: What do retinal Mueller (glial) cells do for their neuronal ‘small siblings’? J Chem Neuroanat 1993;6:201–213.
  9. Poitry S, Poitry-Yamate C, Ueberfeld J, MacLeish PR, Tsacopoulos M: Mechanisms of glutamate metabolic signaling in retinal glial (Mueller) cells. J Neurosci 2000;20:1809–1821.
  10. Li Q, Puro DG: Diabetes-induced dysfunction of the glutamate transporter in retinal Müller cells. Invest Ophthalmol Vis Sci 2002;43:3109–3116.
  11. Kawasaki A, Otori Y, Barnstable CJ: Mueller cell protection of rat retinal ganglion cells from glutamate and nitric oxide neurotoxicity. Invest Ophthalmol Vis Sci 2000;41:3444–3450.
  12. Kajimura M, Shimoyama M, Tsuyama S, Suzuki T, Kozaki S, Takenaka S, Tsubota K, Oguchi Y, Suematsu M: Visualization of gaseous monoxide reception by soluble guanylate cyclase in the rat retina. FASEB J 2003;17:506–508.
  13. Newman EA, Frambach DA, Odette LL: Control of extracellular potassium levels by retinal glial cell K+ siphoning. Science1984;225:1174–1175.
  14. Kusaka S, Dabin I, Barnstable CJ, Puro DG: cGMP-mediated effects on the physiology of bovine and human retinal Mueller (glial) cells. J Physiol 1996;497.3:813–824.
  15. Barabas P, Kovacs I, Kovacs R, Palhalmi J, Kardos J, Schousboe A: Light-induced changes in glutamate release from isolated rat retina is regulated by cyclic guanosine monophosphate. J Neurosci Res 2002;67:149–155.
  16. Ahmad I, Leinders-Zufall T, Kocsis JD, Shepherd GM, Zufall F, Barnstable CJ: Retinal ganglion cells express a cGMP-gated cation conductance activatable by nitric oxide donors. Neuron1994;12:155–165.
  17. Tsuyama S, Yamazaki E, Tomita T, Ihara H, Takenaka S, Kato K, Kozaki S: Characterization of a novel monoclonal antibody that senses nitric oxide-dependent activation of soluble guanylate cyclase. FEBS Lett 1999;455:291–294.
  18. Schaefer S, Kajimura M, Tsuyama S, Uchida K, Sato E, Inoue M, Suematsu M, Watanabe K: Aberrant utilization of nitric oxide and regulation of soluble guanylate cyclase in rat diabetic retinopathy. Antioxid Redox Signal 2003;5:457–465.
  19. Inoue M, Watanabe N: Targeting SOD by gene and protein engineering and inhibition of oxidative stress in various diseases. Adv Exp Med Biol 1990;264:5–12.
  20. Kojima K, Matsubara H, Harada T, Mizuno K, Suzuki M, Hotta N, Kakuta H, Sakamoto N: Effects of aldose reductase inhibitor on retinal microangiopathy in streptozotocin-diabetic rats. Jpn J Ophthalmol 1985;29:99–109.
  21. McCaleb ML, McKean ML, Hohman TC, Laver N, Robinson WG Jr: Intervention with the aldose reductase inhibitor, tolrestat, in renal and retinal lesions of streptozotocin-diabetic rats. Diabetologia1991;34:695–701.
  22. Van Gerven JM, Tjon-A-Tsien AM: The efficacy of aldose reductase inhibitors in the management of diabetic complications: comparison with intensive insulin treatment and pancreatic transplantation. Drugs Aging 1995;6:9–28.
  23. Ido Y, Kilo C, Williamson JR: Cytosolic NADH/NAD+, free radicals, and vascular dysfunction in early diabetes mellitus. Diabetologia 1997;40:S115–S117.
    External Resources
  24. Wolin MS, Mohazzab KM: Mediation of signal transduction by oxidants; in Scandalios JG (ed): Oxidative Stress and the Molecular Biology of Antioxidant Defenses. Cold Spring Harbor, Cold Spring Harbor Laboratory Press, 1997, pp 21–48.
  25. Sakamoto N, Sato Y, Goto Y, Ikeda Y, Takahashi A, Yano S, et al: Treatment of diabetic neuropathy with traditional oriental medicine: comparison between goshajinkigan and mecobalamin treatment (in Japanese). J Jpn Diabet Soc1987;30:729–737.
  26. Nishizawa M, Sutherland WHF, Nukada H: Gosha-jinki-gan (herbal medicine) in streptozotocin-induced diabetic neuropathy. J Neurol Sci 1995;132:177–181.
  27. Toda S: Inhibitory effects of aromatic herbs on the generation of active oxygen (in Japanese). J Med Pharmacol Wakan-Yaku 1991;8:55–58.
  28. Toda S: Inhibitory effects of aromatic herbs on lipid peroxidation and protein oxidative modification by copper. Phytother Res2003;17:546–548.
  29. Suzuki Y, Goto K, Ishige A, Komatsu Y, Kamei J: Effects of gosha-jinki-gan, a Kampo medicine, on peripheral tissue blood flow in streptozotocin-induced diabetic rats. Methodol Find Exp Clin Pharmacol 1998;20:321–328.
  30. Suzuki Y, Goto K, Ishige A, Komatsu Y, Kamei J: Effect of gosha-jinki-gan, a Kampo medicine, on enhanced platelet aggregation in streptozotocin-induced diabetic rats. Jpn J Pharmacol 1998;78:87–91.
  31. Aida K, Shindo H, Tawata M, Onaya T: Inhibition of aldose reductase activities by Kampo medicines. Planta Med 1987;53:131–135.
  32. Aida K, Tawata M, Shindo H, Onaya T, Sasaki H, Nishimura H, Chin M, Mitsuhashi H: The existence of aldose reductase inhibitors in some Kampo medicines (oriental herb prescriptions). Planta Med 1989;55:22–26.
  33. Broadhurst CL, Polansky MM, Anderson RA: Insulin-like biological activity of culinary and medicinal plant aqueous extracts in vitro. J Agric Food Chem 2000;48:849–852.
  34. Imparl-Radosevich J, Deas S, Polansky MM, Baedke DA, Ingebritsen TS, Anderson RA, Graves DJ: Regulation of PTP-1 and insulin receptor kinase by fractions from cinnamon: implications for cinnamon regulation of insulin signaling. Horm Res 1998;50:177–182.
  35. Hu X, Sato J, Oshida Y, Xu M, Bajotto G, Sato Y: Effect of gosha-jinki-gan (Chinese herbal medicine: niu-che-sen-qi-wan) on insulin resistance in streptozotocin-induced diabetic rats. Diabetes Res Clin Pract 2003;59:103–111.
  36. Monograph for Aconitum napellus of the Commission D of the Institut für Arzneimittel of the Federal Ministry of Health. BAZ 1985/190, 5.9.
  37. Purves T, Middlemas A, Agthong S, Jude EB, Boulton AJM, Fernyhough P, Tomlinson DR: A role for mitogen-activated protein kinases in the etiology of diabetic neuropathy. FASEB J 2001;15:2508–2514.
  38. Uchida K, Kanematsu M, Sakai K, Matsuda T, Hattori N, Mizuno Y, Suzuki D, Miyata T, Noguchi N, Niki E, Osawa T: Protein-bound acrolein: potential markers for oxidative stress. Proc Natl Acad Sci USA 1998;95:4882–4887.
  39. Sawa T, Akaike T, Maeda J: Tyrosine nitration by peroxynitrite formed from nitric oxide and superoxide generated by xanthine oxidase. J Biol Chem 2000;275:32467–32474.
  40. Morikawa N, Suematsu M, Kyokane T, Goda N, Kumamoto Y, Okitsu T, Ishimura Y, Kitajima M: Discontinuous total parenteral nutrition prevents postischemic mitochondrial dysjunction in rat liver. Hepatology 1998;28:1289–1299.
  41. Balasubramanian D, Kanwar R: Molecular pathology of dityrosine cross-links in proteins: structural and functional analysis of four proteins. Mol Cell Biochem 2002;234–235:27–38.
  42. Kawai Y, Furuhata A, Toyokuni S, Aratani Y, Uchida K: Formation of acrolein/derived 2′-deoxyadenosine adduct in an iron-induced carcinogenesis model. J Biol Chem 2003;278:50346–50354.
  43. Tanel A, Averill-Bates DA: The aldehyde acrolein induces apoptosis via activation of the mitochondrial pathway. Biochim Biophys Acta 2005;1743:255–267.
  44. Sobrevia L, Nadal A, Yudilevich DL, Mann GE: Activation of L-arginine transport (system y+) and nitric oxide synthase by elevated glucose and insulin in human endothelial cells. J Physiol 1996;490.3:775–781.
  45. Mitamura M, Horie S, Sakaguchi M, Someya A, Tsuchiya S, Van de Voorde J, Murayama T, Watanabe K: Mesaconitine-induced relaxation in rat aorta: involvement of Ca2+ influx and nitric-oxide synthase in the endothelium. Eur J Pharmacol 2002;436:217–225.
  46. Kahn NN, Acharya K, Bhattacharya S, Acharya R, Mazumder S, Bauman WA, Sinha AK: Nitric oxide: the ‘second messenger’ of insulin. IUBMB Life2000;49:441–450.
  47. Kobayashi T, Kamata K: Effect of chronic insulin treatment on NO production and endothelium-dependent relaxation in aortae from established STZ-induced diabetic rats. Atherosclerosis 2001;155:313–321.
  48. Huang Q, Shao L, Jiang H, Miao ZC, Shi QD, Liu SS: Effect of insulin on oxygen free radicals and oxidative phosphorylation in liver mitochondria of diabetic rats. Acta Pharmacol Sin 2001;22:455–458.
  49. Chen HC, Guh JY, Shin SJ, Tsai JH, Lai YH: Insulin and heparin suppress superoxide production in diabetic rat glomeruli stimulated with low-density lipoprotein. Kidney Int Suppl2001;78:S124–S127.
    External Resources
  50. Peng Q, Wei Z, Lau BH: Fructus corni enhances endothelial cell antioxidant defenses. Gen Pharmacol 1998;31:221–225.
  51. Obrosova I, Faller A, Burgan J, Ostrow E, Williamson JR: Glycolytic pathway, redox state of NAD(P)-couples and energy metabolism in lens in galactose-fed rats: effect of an aldose reductase inhibitor. Curr Eye Res 1997;16:34–43.
  52. Obrosova IG, Stevens MJ, Lang HJ: Diabetes-induced changes in retinal NAD-redox status: pharmacological modulation and implications for pathogenesis of diabetic retinopathy. Pharmacology 2001;62:172–180.
  53. Obrosova IG, Pacher P, Szabo C, Zsengeller Z, Hirooka H, Stevens MJ, Yorek M: Aldose reductase inhibition counteracts oxidative-nitrosative stress and poly(ADP-ribose) polymerase activation in tissue sites for diabetes complications. Diabetes 2005;54:234–242.
  54. DCCT Research Group: Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol1998;116:874–876.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: June 09, 2005
Accepted: August 29, 2005
Published online: March 01, 2006
Issue release date: February 2006

Number of Print Pages: 10
Number of Figures: 5
Number of Tables: 0

ISSN: 0030-3747 (Print)
eISSN: 1423-0259 (Online)

For additional information: https://www.karger.com/ORE


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