Publications & Abstracts


Clinical and Preclinical Activities of PYRIDORIN® (pyridoxamine dihydrochloride)

  1. Lewis EJ, Greene T, Spitalewiz S, Blumenthal S, Berl T, Hunsicker L, Pohl MA, Rohde RD, Raz I, Yerushalmy Y, Yagil Y, Herskovitz T, Packham DK, Lewis JB. Pyridorin in Type 2 Diabetic Nephropathy. J Am Soc Nephrol 23(1):131-6, 2012. Epub 2011 Oct 27.
  2. Williams ME, Bolton K, Khalifah RG, Degenhardt TP, Schotzinger RJ; McGill Janet B. Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy. Am J Nephrol. 27:605-14, 2007.
  3. Tanimoto M, Gohda T, Kaneko S, Hagiwara S, Murakoshi M, Aoki T, Yamada K, Ito T, Matsumoto M, Horikoshi S, Tomino Y. Effect of pyridoxamine (K-163), an inhibitor of advanced glycation end products, on type 2 diabetic nephropathy in KK-A(y)/Ta mice. Metabolism. 56:160-7, 2007.
  4. Zheng F, Zeng YJ, Plati AR, Elliot SJ, Berho M, Potier M, Striker LJ, Striker GE. Combined AGE inhibition and ACEi decreases the progression of established diabetic nephropathy in B6 db/db mice. Kidney Int. 70:507-14, 2006.
  5. Kakuta T, Tanaka R, Satoh Y, Izuhara Y, Inagi R, Nangaku M, Saito A, Miyata T. Pyridoxamine improves functional, structural, and biochemical alterations of peritoneal membranes in uremic peritoneal dialysis rats. Kidney Int. 68:1326-36, 2005.
  6. Metz TO, Alderson NL, Chachich ME, Thorpe SR, Baynes JW. Pyridoxamine traps intermediates in lipid peroxidation reactions in vivo: evidence on the role of lipids in chemical modification of protein and development of diabetic complications. J Biol Chem. 278:42012-9, 2003.
  7. Alderson NL, Chachich ME, Youssef NN, Beattie RJ, Nachtigal M, Thorpe SR, Baynes JW. The AGE inhibitor pyridoxamine inhibits lipemia and development of renal and vascular disease in Zucker obese rats. Kidney Int. 63:2123-33, 2003.
  8. Stitt A, Gardiner TA, Alderson NL, Canning P, Frizzell N, Duffy N, Boyle C, Januszewski AS, Chachich M, Baynes JW, Thorpe SR. The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental diabetes. Diabetes. 51:2826-32, 2002.
  9. Canning P, Glenn JV, Hsu DK, Liu FT, Gardiner TA, Stitt AW. Inhibition of advanced glycation and absence of galectin-3 prevent blood-retinal barrier dysfunction during short-term diabetes. Exp Diabetes Res. 2007:51837, 2007.
  10. Degenhardt TP, Alderson NL, Arrington DD, Beattie RJ, Basgen JM, Steffes MW, Thorpe SR, Baynes JW. Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin-diabetic rat. Kidney Int. 61:939-50, 2002.
  11. Nagaraj RH, Sarkar P, Mally A, Biemel KM, Lederer MO, Padayatti PS. Effect of pyridoxamine on chemical modification of proteins by carbonyls in diabetic rats: characterization of a major product from the reaction of pyridoxamine and methylglyoxal. Arch Biochem Biophys. 402:110-9, 2002.

Mechanism of Pyridorin®

  1. Khalifah RG, Baynes JW, Hudson BG. Amadorins: novel post-Amadori inhibitors of advanced glycation reactions. Biochem Biophys Res Commun. 257:251-8, 1999.
  2. Voziyan PA, Hudson BG. Pyridoxamine as a multifunctional pharmaceutical: targeting pathogenic glycation and oxidative damage. Cell Mol Life Sci. 62:1671-81, 2005.
  3. Metz TO, Alderson NL, Thorpe SR, Baynes JW. Pyridoxamine, an inhibitor of advanced glycation and lipoxidation reactions: a novel therapy for treatment of diabetic complications. Arch Biochem Biophys. 419:41-9, 2003.
  4. Voziyan PA, Khalifah RG, Thibaudeau C, Yildiz A, Jacob J, Serianni AS, Hudson BG. Modification of proteins in vitro by physiological levels of glucose: pyridoxamine inhibits conversion of Amadori intermediate to advanced glycation end-products through binding of redox metal ions. J Biol Chem. 278:46616-24, 2003.
  5. Booth AA, Khalifah RG, Todd P, Hudson BG. In vitro kinetic studies of formation of antigenic advanced glycation end products (AGEs). Novel inhibition of post-Amadori glycation pathways. J Biol Chem. 272:5430-7, 1997.
  6. Voziyan PA, Metz TO, Baynes JW, Hudson BG. A post-Amadori inhibitor pyridoxamine also inhibits chemical modification of proteins by scavenging carbonyl intermediates of carbohydrate and lipid degradation. J Biol Chem. 277:3397-403, 2002.
  7. Monnier VM. Intervention against the Maillard reaction in vivo. Arch Biochem Biophys. 419:1-15, 2003.
  8. Khalifah RG, Chen Y, Wassenberg JJ. Post-Amadori AGE inhibition as a therapeutic target for diabetic complications: a rational approach to second-generation Amadorin design. Ann N Y Acad Sci. 1043:793-806, 2005.
  9. Yang S, Litchfield JE, Baynes JW. AGE-breakers cleave model compounds, but do not break Maillard crosslinks in skin and tail collagen from diabetic rats. Arch Biochem Biophys. 412:42-6, 2003.
  10. Chetyrkin S, Mathis M, Hayes McDonald W, Shackelford X, Hudson B, Voziyan P: Pyridoxamine protects protein backbone from oxidative fragmentation. Biochemical and biophysical research communications. 411:574-579, 2011.
  11. Chetyrkin SV, Mathis ME, Ham AJ, Hachey DL, Hudson BG, Voziyan PA: Propagation of protein glycation damage involves modification of tryptophan residues via reactive oxygen species: Inhibition by pyridoxamine. Free radical biology & medicine. 44:1276-1285, 2008.
  12. Chetyrkin SV, Zhang W, Hudson BG, Serianni AS, Voziyan PA: Pyridoxamine protects proteins from functional damage by 3-deoxyglucosone: Mechanism of action of pyridoxamine. Biochemistry. 47:997-1006, 2008.
  13. Davies SS, Brantley EJ, Voziyan PA, Amarnath V, Zagol-Ikapitte I, Boutaud O, Hudson BG, Oates JA, Roberts LJ, 2nd: Pyridoxamine analogues scavenge lipid-derived gamma-ketoaldehydes and protect against h202-mediated cytotoxicity. Biochemistry. 45:15756-15767, 2006.

Oxidative Chemistries and Reactive Carbonyls as Significant Pathogenic Factors

  1. Nishikawa T, Edelstein D, Brownlee M. The missing link: a single unifying mechanism for diabetic complications. Kidney Int Suppl 77:S26-30, 2000.
  2. Genuth S, Sun W, Cleary P, Sell DR, Dahms W, Malone J, Sivitz W, Monnier VM; DCCT Skin Collagen Ancillary Study Group. Glycation and carboxymethyllysine levels in skin collagen predict the risk of future 10-year progression of diabetic retinopathy and nephropathy in the diabetes control and complications trial and epidemiology of diabetes interventions and complications participants with type 1 diabetes. Diabetes 54:3103-11, 2005.
  3. Tan AL, Forbes JM, Cooper ME. AGE, RAGE, and ROS in diabetic nephropathy. Semin Nephrol. 27:130-43, 2007.
  4. Beisswenger PJ, Drummond KS, Nelson RG, Howell SK, Szwergold BS, Mauer M. Susceptibility to diabetic nephropathy is related to dicarbonyl and oxidative stress. Diabetes 54:3274-81, 2005.
  5. Bohlender JM, Franke S, Stein G, Wolf G. Advanced glycation end products and the kidney. Am J Physiol Renal Physiol. 289:F645-59, 2005.
  6. Williams ME, Tuttle KR. The next generation of diabetic nephropathy therapies: an update. Adv Chronic Kidney Dis. 12:212-22, 2005.
  7. Heidland A, Sebekova K, Schinzel R. Advanced glycation end products and the progressive course of renal disease. Am J Kidney Dis. 38 (Suppl 1):S100-6, 2001.
  8. Raj DS, Choudhury D, Welbourne TC, Levi M. Advanced glycation end products: a Nephrologist’s perspective. Am J Kidney Dis. 35:365-80, 2000.
  9. Suzuki D, Miyata T. Carbonyl stress in the pathogenesis of diabetic nephropathy. Intern Med. 38:309-14, 1999.
  10. Tanji N, Markowitz GS, Fu C, Kislinger T, Taguchi A, Pischetsrieder M, Stern D, Schmidt AM, D’Agati VD. Expression of advanced glycation end products and their cellular receptor RAGE in diabetic nephropathy and nondiabetic renal disease. J Am Soc Nephrol. 11:1656-66, 2000.
  11. Thomas MC: Advanced glycation end products. Contributions to nephrology. 170:66-74, 2011.
  12. Giacco F, Brownlee M: Oxidative stress and diabetic complications. Circulation research. 107:1058-1070, 2010.
  13. Chilelli NC, Burlina S, Lapolla A: Ages, rather than hyperglycemia, are responsible for microvascular complications in diabetes: A “glycoxidation-centric” point of view. Nutrition, metabolism, and cardiovascular diseases. 23:913-919, 2013.