Glutathione levels are reduced in diabetic rat retina but are not influenced by ischemia followed by recirculation

Agardh, Carl‐David; Agardh, Elisabet; Qian, Yuning; Hultberg, Björn

doi:10.1016/s0026-0495(98)90255-4

Cited by 25 publications

(11 citation statements)

References 24 publications

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“…Early increase in lipid peroxidation in the retina, unlike other tissues of streptozotocin-diabetic rats [9±11, 40,65], occurs in the absence of glutathione [66] and in our studies, taurine and ascorbate depletion or changes in the glutathione and ascorbate redox states. Despite total arrest of diabetes-induced retinal lipid peroxidation by both antioxidants, dl-alipoic acid completely prevented, whereas taurine only attenuated, VEGF up regulation.…”

Section: Discussionsupporting

confidence: 56%

Antioxidants attenuate early up regulation of retinal vascular endothelial growth factor in streptozotocin-diabetic rats

et al. 2001

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Aims/hypothesis. A strong positive correlation has been found between lipid peroxidation product and vascular endothelial growth factor concentrations in the vitreous of patients with proliferative diabetic retinopathy. To establish a causal relation between diabetes-associated enhanced oxidative stress and vascular endothelial growth factor production, we evaluated two antioxidants, dl-a-lipoic acid and taurine, on retinal vascular endothelial growth factor protein and mRNA expression and on parameters of oxidative stress in streptozotocin-diabetic rats. Methods. Our experiments were on control rats and streptozotocin-diabetic rats with a 6-week duration of diabetes, treated with or without dl-a-lipoic acid (100 mg´kg ±1´d±1 , i. p.) or taurine (1 % in the diet) starting from induction of diabetes. Vascular endothelial growth factor protein in retinal homogenates was assessed by sandwich ELISA with an affinity-purified polyclonal antibody and vascular endothelial growth factor mRNA by ribonuclease protection assay. Retinal lipid peroxidation products i. e. malondialdehyde plus 4-hydroxyalkenals were quantified with n-methyl-2-phenylindole. Retinal reduced and oxidized glutathione, ascorbate, dehydroascorbate, and sorbitol pathway intermediates were measured spectrofluorometrically, and taurine by reverse-phase HPLC.Results. Vascular endothelial growth factor protein concentration (means SD) was increased in diabetic rats compared with control rats (33 7 vs 19 5 pg/mg total protein, p < 0.01) This increase was attenuated by taurine (26 8, p < 0.05) and prevented by dla-lipoic acid (21 4, p < 0.01). Vascular endothelial growth factor mRNA abundance was reduced by 1.4-fold in diabetic rats compared with control rats and this decrease was attenuated but not completely prevented by both antioxidants. Malondialdehyde plus 4-hydroxyalkenal concentration was increased in diabetic rats compared with control rats, and both antioxidants arrested accumulation of lipid peroxidation products. Taurine, reduced glutathione, oxidized glutathione, ascorbate, dehydroascorbate and sorbitol pathway intermediate concentrations as well as oxidized glutathione/reduced glutathione and dehydroascorbate/ascorbate ratios were similar in control and diabetic rats treated with or without taurine. Conclusion/interpretation. Oxidative stress is directly involved in up regulation of vascular endothelial growth factor protein in the retina during early diabetes. [Diabetologia (2001

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Section: Discussionsupporting

confidence: 56%

Antioxidants attenuate early up regulation of retinal vascular endothelial growth factor in streptozotocin-diabetic rats

et al. 2001

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“…However, only a few studies have dealt with the endogenous antioxidant system in the retina, for example, in Muller cells subjected to oxidative stress [36] and in retina subjected to ischemia-reperfusion injury [37][38][39]. In the present study, we demonstrate that retinal ischemia followed by reperfusion induces only a slight change in endogenous antioxidant enzyme expressions.…”

Section: Discussionsupporting

confidence: 48%

Expression of antioxidant enzymes in rat retinal ischemia followed by reperfusion

Agardh¹,

Gustavsson²,

Hagert³

et al. 2006

Metabolism

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To evaluate the expression and protein levels of antioxidant enzymes in the rat retina exposed to oxidative stress induced by ischemia-reperfusion injury. Retinal ischemia was induced in female Wistar rats by ligation of the optic nerve and vessels behind the left eye bulb, and was followed by reperfusion for 0, 3, 6, or 24 hours. The right eye served as control. RNA and protein were extracted simultaneously from each retina. Expressions of the endogenous antioxidant enzymes glutathione peroxidase (GPx1), catalase (CAT), copper/zinc superoxide dismutase, manganese superoxide dismutase, and the catalytic subunit of glutamylcysteine ligase (GCLc) were analyzed with real-time reverse transcription polymerase chain reaction and related to the endogenous control cyclophilin B. Protein levels were measured with Western blot analysis. During the early phase (0 or 3 hours) of reperfusion, no changes were seen in enzyme expression. After 6 hours, GCLc expression increased by a factor of 1.14 (P = 0.034), followed by a decline of 0.80 after 24 hours (P = 0.00004), according to the comparative Ct method. After 24 hours of reperfusion, GPx1 expression increased by a factor of 1.14 (P = 0.028), and CAT had decreased by 0.82 (P = 0.022). Expressions of copper/zinc superoxide dismutase and manganese superoxide dismutase showed a tendency toward a decrease by factors of 0.86 (P = 0.055) and 0.88 (P = 0.053), respectively, after 24 hours.Protein levels did not differ for any of the antioxidants, regardless of reperfusion time. The slightly increased messenger RNA expression of GPx1 after 24 hours of reperfusion with a concomitant very modest decrease in CAT and GCLc expression and no change in protein levels indicate a very modest, if any, response to oxidative stress generated by ischemia followed by reperfusion in rat retina.

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“…The absence of either ascorbate depletion or changes in ascorbate redox state in the retina in early diabetes is consistent with uncompromised GSH levels and GSSG/GSH ratios (Agardh et al, 1998;Obrosova et al, 2000a,b). GSH and other cellular thiols (such as dihydrolipoic acid, the reduced form of a-lipoate) play an important role in vitamin C homeostasis by regenerating AA from DHAA and semiascorbyl radicals (Packer, 1994;Maitra et al, 1995).…”

supporting

confidence: 54%

“…Studies of nonenzymatic antioxidants in rat retina resulted in contradictory ®ndings. The reduced glutathione (GSH) levels, reported by Kern, Kowluru and Engerman (1995), are at least three-fold higher than those of three other groups (Organisciak, Wang and Kou, 1984;Agardh et al, 1998;Obrosova et al, 2000a,b). Furthermore, Kern et al, 1995, observed a decrease in GSH level in early diabetes whereas others (Agardh et al, 1998;Obrosova et al, 2000a,b) failed to ®nd these changes.…”

mentioning

confidence: 89%

“…The reduced glutathione (GSH) levels, reported by Kern, Kowluru and Engerman (1995), are at least three-fold higher than those of three other groups (Organisciak, Wang and Kou, 1984;Agardh et al, 1998;Obrosova et al, 2000a,b). Furthermore, Kern et al, 1995, observed a decrease in GSH level in early diabetes whereas others (Agardh et al, 1998;Obrosova et al, 2000a,b) failed to ®nd these changes. Taurine levels were found similar in control rats and rats with streptozotocin diabetes of 1 month duration (Vilchis and Salceda, 1996).…”

mentioning

confidence: 89%

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Increased Retinal Lipid Peroxidation in Early Diabetes is not Associated with Ascorbate Depletion or Changes in Ascorbate Redox State

Fathallah

Obrosova

2001

Experimental Eye Research

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Glutathione levels are reduced in diabetic rat retina but are not influenced by ischemia followed by recirculation

Cited by 25 publications

References 24 publications

Antioxidants attenuate early up regulation of retinal vascular endothelial growth factor in streptozotocin-diabetic rats

Antioxidants attenuate early up regulation of retinal vascular endothelial growth factor in streptozotocin-diabetic rats

Expression of antioxidant enzymes in rat retinal ischemia followed by reperfusion

Increased Retinal Lipid Peroxidation in Early Diabetes is not Associated with Ascorbate Depletion or Changes in Ascorbate Redox State

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