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Pharmaceutical intervention of advanced glycation endproducts

Pharmaceutical intervention of advanced glycation endproducts.In this study， 341028-37-3 and 5304-34-7 are also used. Cerami, Anthony; Ulrich, Peter (The Kenneth S. Warren Laboratories, Tarrytown, NY 10591, USA). Novartis Foundation Symposium, 235(Aging Vulnerability), 202-216 (English) 2001 John Wiley & Sons Ltd. CODEN: NFSYF7. ISSN: 1528-2511. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) Section cross-reference(s): 14 A review. Recent studies have revealed that reducing sugars, such as glucose, react with proteins through non-enzymic glycosylation to form irreversible, covalently crosslinked proteins known as advanced glycation endproducts (AGEs). Furthermore, it has been demonstrated that this naturally occurring process, accelerated in diabetics due to hyperglycemia, impairs biol. functions leading to cardiovascular disorders, as well as diabetic and age-related complications. Pharmaceutical intervention to prevent or reverse these complications have focused on inhibiting the formation of AGEs by compds. such as dimethyl-3-phenacylthiazolium chloride or breaking the glucose derived crosslinks by selective cleavage. Intervention targeted at AGE crosslinks in vivo offers a way to interfere with age-related changes of tissues. .

Prevention and Reversal of Diabetic Nephropathy in db/db Mice Treated with Alagebrium (ALT-711)

All Rights Reserved. Prevention and Reversal of Diabetic Nephropathy in db/db Mice Treated with Alagebrium (ALT-711). Peppa, Melpomeni; Brem, Harold; Cai, Weijing; Zhang, Jiang-Gang; Basgen, John; Li, Zhu; Vlassara, Helen; Uribarri, Jaime (Department of Geriatrics, Mount Sinai School of Medicine, New York, NY, USA). American Journal of Nephrology, 26(5), 430-436 (English) 2006 S. Karger AG. CODEN: AJNED9. ISSN: 0250-8095. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Background: Alagebrium (ALT-711) has been shown to improve renal dysfunction in animal models of diabetes. Methods: To test its effects in diabetic nephropathy (DN), ALT-711 was administered (1 mg/kg daily i.p.) to 9-wk-old female db/db mice (n = 15, group A1) for 3 wk and to 3-mo-old (n = 15, group A2), 7-mo-old (n = 7, group A3), and 12-mo-old (n = 5, group A4) female db/db mice for 12 wk, while a similar no. of diabetic and nondiabetic mice were used as controls. The eN-carboxymethyllysine (CML) levels in serum, urine, skin, and kidney tissue were measured by ELISA. The renal morphometric parameters were assessed by electron and light microscopy. Results: By the 3rd week of treatment, the serum CML level decreased by 41%, and the urinary CML concn. increased by 138% from baseline, while the urinary albumin/creatinine ratio was lower (p < 0.05) in diabetic and nondiabetic group A1 mice. After 3 mo of treatment, serum, skin, and kidney CML levels and urinary albumin/creatinine ratio were lower (p < 0.05) and the urinary CML levels higher (p < 0.There are some commonly used reagents with their cas registry numbers 341028-37-3 and 5746-04-3 in this article.05) in treated group A2, A3, and A4 animals compared with groups which received phosphate-buffered saline, with a similar pattern obsd. in nondiabetic mice. The renal morphol. parameters characteristic of DN decreased in treated compared with untreated mice. Conclusion: Alagebrium may prevent, delay, and/or reverse established DN in db/db mice by reducing the systemic advanced glycation end product pools and facilitating the urinary excretion of advanced glycation end products. .