Can allopurinol improve retinopathy in diabetic rats? Oxidative stress or uric acid; which one is the culprit?

Goharinia, Mohsen; Zareei, Athar; Rahimi, Masoud; Mirkhani, Hossein

doi:10.4103/1735-5362.213985

Cited by 10 publications

(3 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with this evidence, allopurinol, which specifically blocks XOD ( 32 ), showed greater ability to prevent retinal inflammation than benzbromarone, which primarily exert systemic UA levels by increasing its urinary excretion ( 33 ). Additional effects of allopurinol may also involve decreased retinal oxidative stress due to XOD blockade ( 49 ).…”

Section: Discussionmentioning

confidence: 99%

Monosodium Urate Contributes to Retinal Inflammation and Progression of Diabetic Retinopathy

et al. 2019

View full text Add to dashboard Cite

We have investigated the contributing role of monosodium urate (MSU) to the pathological processes associated with the induction of diabetic retinopathy (DR). In human postmortem retinas and vitreous from donors with DR, we have found a significant increase in MSU levels that correlated with the presence of inflammatory markers and enhanced expression of xanthine oxidase. The same elevation in MSU levels was also detected in serum and vitreous of streptozotocin-induced diabetic rats (STZ-rats) analyzed at 8 weeks of hyperglycemia. Furthermore, treatments of STZ-rats with the hypouricemic drugs allopurinol (50 mg/kg) and benzbromarone (10 mg/kg) given every other day resulted in a significant decrease of retinal and plasma levels of inflammatory cytokines and adhesion factors, a marked reduction of hyperglycemia-induced retinal leukostasis, and restoration of retinal blood-barrier function. These results were associated with effects of the hypouricemic drugs on downregulating diabetes-induced levels of oxidative stress markers as well as expression of components of the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome such as NLRP3, Toll-like receptor 4, and interleukin-1β. The outcomes of these studies support a contributing role of MSU in diabetes-induced retinal inflammation and suggest that asymptomatic hyperuricemia should be considered as a risk factor for DR induction and progression.

show abstract

Section: Discussionmentioning

confidence: 99%

Monosodium Urate Contributes to Retinal Inflammation and Progression of Diabetic Retinopathy

et al. 2019

View full text Add to dashboard Cite

show abstract

“…It contributes to insulin deficiency ( 28 ) and causes insulin signals inhibition through adipocytokine ( 29 ). Hyperlipoproteinemia and hyperglycemia are usually accompanied by diabetes caused by STZ due to chronic oxidative stress ( 30 31 ). In addition, neurologic complications ( 32 ) and nephropathy are also included in this disease ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Chrysin ameliorates STZ-induced diabetes in rats

Salama

Asaad

Shaheen

2022

Research in Pharmaceutical Sciences

View full text Add to dashboard Cite

Background and purpose: Growing evidence advocates that upregulation of toll-like receptor 4 (TLR4) has been suggested as a causative influence in the development and complications of diabetes mellitus. We aimed to study the antidiabetic activity of chrysin against streptozotocin (STZ)-induced diabetes via down-regulation of TLR4/nuclear factor (NF-κβ)/heat shock protein 70 (HSP70) pathway as well as modulation of clusters of differentiation 4 (CD4+) in rats. Experimental approach: Fifty rats were divided into five groups (n = 10). Group I, normal rats received a single intraperitoneal injection of buffer citrate; group II, STZ-induced diabetic rats; groups III-V, diabetic rats received glimepiride (0.5 mg/kg; p.o.) or chrysin (40 and 80 mg/kg; p.o.) respectively, for 10 days. Serum samples were extracted to determine nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH), insulin, CD4+, TLR4, and NF-κβ. Pancreatic tissue samples were extracted to determine glucose transporter 2 (GLUT2). Part of the pancreas was kept in formalin for pathological studies. Findings/Results: An elevation in blood glucose, NO, and MDA serum levels and a reduction of pancreatic GLUT2 content, insulin, and GSH serum levels were observed in diabetic rats. STZ injection, also, showed an increase in serum TLR4, NF-κβ, and HSP70 levels and a reduction in serum CD4+ levels with pancreatic cells necrosis. These biochemical and histological changes were reversed in glimepiride and chrysin groups. Conclusion and implications: The present study proved that chrysin has a potent anti-diabetic effect through the elevation of insulin and GLUT2 levels, the reduction of oxidative stress, and the inflammatory pathways TLR4/NF-κβ/HSP70 with the regulation of CD4+.

show abstract

“…Oxidative stress is involved in retinal neurodegeneration in diabetes (Giacco & Brownlee, 2010;Mesquida et al, 2019) and increased uric acid has been implicated in the pathology of DME (Krizova et al, 2011(Krizova et al, , 2015. In an experimental DR model, allopurinol was shown to reduce oxidative stress (Goharinia et al, 2017). In another paper, the treatment of STZ rats with the hypouricemic drugs allopurinol and benzbromarone decreased retinal levels of inflammatory cytokines and adhesion factors and prevented retinal vascular permeability and hyperglycemia-induced retinal leukostasis (Thounaojam et al, 2019).…”

Section: Allopurinolmentioning

confidence: 99%

Development of diabetic macular oedema shows associations with systemic medication – An epidemiological study

Loukovaara,

Korhonen,

Niskanen

et al. 2023

Acta Ophthalmologica

View full text Add to dashboard Cite

PurposeTo identify associations between systemic drugs and the incidence of diabetic macular oedema (DME). Of interest was to find beneficial and/or deleterious associations of used drugs.MethodsA historic cohort design based on administrative data. Study population consisted of 150 353 individuals with diabetes. Endpoint event was the development of DME (ICD‐10 H36.01), censoring events were death or study end December 2017. The follow‐up started between 1997 and 2010. The systemic medication consisted of 95 substances. We constructed a nested case–control study design comparing 2630 cases with DME to 13 144 age‐ and sex‐matched controls without DME. Results are reported as odds ratios (ORs) with 95% confidence intervals (CIs) based on conditional logistic regression models.ResultsIncidence rate for DME was 1.80 per 1000 person‐years (95% CI 1.73–1.87). In all, we observed a lower incidence rate of DME in females (IRR 0.57; 95% CI 0.52–0.62) compared to males. Exposure to hormone replacement therapy estradiol (OR 0.42; 0.25–0.68), temazepam (0.23; 0.08–0.62) and allopurinol (0.61; 0.43–0.86) were associated with lower risk of DME, while use of insulin or insulin analogue (3.30; 2.99–3.64), sulfonylureas (1.21; 1.05–1.40), diuretic furosemide (1.90; 1.61–2.24), calcium channel blocker amlodipine (1.53; 1.34–1.75), ACE inhibitors ramipril (1.66; 1.46–1.89) and enalapril (1.38; 1.16–1.64) were associated with an increased risk of DME.ConclusionsLarge‐scale studies examining the incidence of DME are lacking. Our findings suggest that associations of systemic medications with the incidence of DME may shed light on the pathogenesis of complex DME, encouraging further studies.

show abstract

Can allopurinol improve retinopathy in diabetic rats? Oxidative stress or uric acid; which one is the culprit?

Cited by 10 publications

References 33 publications

Monosodium Urate Contributes to Retinal Inflammation and Progression of Diabetic Retinopathy

Monosodium Urate Contributes to Retinal Inflammation and Progression of Diabetic Retinopathy

Chrysin ameliorates STZ-induced diabetes in rats

Development of diabetic macular oedema shows associations with systemic medication – An epidemiological study

Contact Info

Product

Resources

About