ArticleDiabetologia2008
LR-90 prevents dyslipidaemia and diabetic nephropathy in the Zucker diabetic fatty rat.
Article in Diabetologia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 50 citations in OpenAlex.
- Diabetic Kidney Disease: From Pathogenesis to Novel Treatment Possibilities.Handbook of experimental pharmacology · 2022Review
- Inhibitors of Advanced Glycation End Product (AGE) Formation and Accumulation.Handbook of experimental pharmacology · 2021Article
- Treatment with adipose tissue-derived mesenchymal stem cells exerts anti-diabetic effects, improves long-term complications, and attenuates inflammation in type 2 diabetic rats.Stem cell research & therapy · 2019Article
- Effects of vitamin D supplementation on advanced glycation end products signaling pathway in T2DM patients: a randomized, placebo-controlled, double blind clinical trial.Diabetology & metabolic syndrome · 2019Article
- Article
- FPS-ZM1 and valsartan combination protects better against glomerular filtration barrier damage in streptozotocin-induced diabetic rats.Journal of physiology and biochemistry · 2018Article
- Effects of xanthine oxidase inhibition with febuxostat on the development of nephropathy in experimental type 2 diabetes.British journal of pharmacology · 2016Article
- Targeting advanced glycation with pharmaceutical agents: where are we now?Glycoconjugate journal · 2016Review
- New molecular insights in diabetic nephropathy.International urology and nephrology · 2016Review
- Chronic NF-κB blockade improves renal angiotensin II type 1 receptor functions and reduces blood pressure in Zucker diabetic rats.Cardiovascular diabetology · 2015Article
- Effects of a new advanced glycation inhibitor, LR-90, on mitigating arterial stiffening and improving arterial elasticity and compliance in a diabetic rat model: aortic impedance analysis.British journal of pharmacology · 2014Article
- Advances in murine models of diabetic nephropathy.Journal of diabetes research · 2013Review
- Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications.Diabetes · 2012Review
- Prediabetic nephropathy as an early consequence of the high-calorie/high-fat diet: relation to oxidative stress.Endocrinology · 2012Article
- Discovery of genes related to diabetic nephropathy in various animal models by current techniques.Contributions to nephrology · 2011Article
- Poly(ADP-ribose) polymerase-1 (PARP-1) gene deficiency alleviates diabetic kidney disease.Biochimica et biophysica acta · 2010Article
- Poly(Adenosine 5'-diphosphate-ribose) polymerase inhibition counteracts multiple manifestations of experimental type 1 diabetic nephropathy.Endocrinology · 2009Article
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6 authors at 1 institution in 1 country.
Funding
Abstract
aims/hypothesisPrevious studies have shown that LR-90, a new inhibitor of AGE formation, prevented the development of experimental type 1 diabetic nephropathy. In this study, we examined the effects of LR-90 in the Zucker diabetic fatty (ZDF) rat, a model of type 2 diabetes and metabolic syndrome, and investigated the mechanisms by which it may protect against renal injury.
methodsMale ZDF rats were treated without or with LR-90 from age 13 to 40 weeks. Metabolic and kidney functions and renal histology were evaluated. AGE accumulation and the production of the receptor for AGE (AGER) were measured. Profibrotic growth factors, extracellular matrix proteins and intracellular signalling pathways associated with glomerular and tubular damage were also analysed.
resultsLR-90 dramatically reduced plasma lipids in ZDF rats, with only modest effects on hyperglycaemia. Renal AGE, AGER and lipid peroxidation were all attenuated by LR-90. LR-90 significantly retarded the increase in albuminuria and proteinuria. This was associated with reduction in glomerulosclerosis and tubulointerstitial fibrosis, concomitant with marked inhibition of renal overproduction of TGF-beta1, connective tissue growth factor, fibronectin and collagen IV. Additionally, LR-90 downregulated the activation of key mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-kappaB) in the renal cortex. CONCLUSIONS/
interpretationThese results support our earlier studies on the renoprotective effects of LR-90 on type 1 diabetic nephropathy and provide further evidence that LR-90, an AGE inhibitor with pleiotrophic effects, may also be beneficial for the prevention of type 2 diabetic nephropathy, where multiple risk factors, such as hyperglycaemia, dyslipidaemia, obesity, insulin resistance and hypertension, contribute to renal injury.
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