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2011 | 58 | 1 | 75-77
Article title

Effects of 1-methylnicotinamide and its metabolite N-methyl-2-pyridone-5-carboxamide on streptozotocin-induced toxicity in murine insulinoma MIN6 cell line

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1-methylnicotinamide (MNA) is a primary metabolite of nicotinamide. In recent years several activities of MNA have been described, such as anti-inflammatory activity in skin diseases, induction of prostacyclin synthesis via COX-2, aortal endothelium protection in diabetes and hypertriglyceridaemia and increased survival rate of diabetic rats. 1-methylnicotinamide was also suggested to protect pancreatic cells from streptozotocin in vivo. Streptozotocin toxicity is known to be mediated by poly-ADP-ribose polymerase. Nicotinamide and its derivatives have been shown to ameliorate poly-ADP-ribose polymerase-dependent nucleotide pool reduction. We aimed to verify if 1-methylnicotinamide and its metabolite, N-methyl-2-pyridone-5-carboxamide, can protect insulinoma cells from streptozotocin-induced toxicity. We found that N-methyl-2-pyridone-5-carboxamide, but not 1-methylnicotinamide, restores the pool of ATP and NAD+ in streptozotocin-treated cells, but neither compound improved the cell viability. We conclude that inhibition of poly-ADP-ribose polymerase-dependent nucleotide pool reduction may not be sufficient to protect cells from streptozotocin toxicity.
Physical description
  • Department of Haemostasis and Haemostatic Disorders, Chair of Laboratory Diagnostics, Medical University of Lodz, University Clinical Hospital No 2, Łódź, Poland
  • Department of Biochemistry, Medical University of Gdansk, Gdańsk, Poland
  • Department of Pediatrics, Medical University of Lodz, Łódź, Poland
  • Department of Pediatrics, Medical University of Lodz, Łódź, Poland
  • Department of Haemostasis and Haemostatic Disorders, Chair of Laboratory Diagnostics, Medical University of Lodz, University Clinical Hospital No 2, Łódź, Poland
  • Bartus M, Lomnicka M, Kostogrys RB, Kazmierczak P, Watala C, Slominska EM, Smolenski RT, Pisulewski PM, Adamus J, Gebicki J, Chlopicki S (2008) 1-Methylnicotinamide (MNA) prevents endothelial dysfunction in hypertriglyceridemic and diabetic rats. Pharmacol Rep 60: 127-138.
  • Burkart V, Wang ZQ, Radons J, Heller B, Herceg Z, Stingl L, Wagner EF, Kolb H (1999) Mice lacking the poly(ADP-ribose) polymerase gene are resistant to pancreatic beta-cell destruction and diabetes development induced by streptozocin. Nat Med 5: 314-319.
  • Chlopicki S, Swies J, Mogielnicki A, Buczko W, Bartus M, Lomnicka M, Adamus J, Gebicki J (2007) 1-Methylnicotinamide (MNA) a primary metabolite of nicotinamide exerts anti-thrombotic activity mediated by a cyclooxygenase-2/prostacyclin pathway. Br J Pharmacol 152: 230-239.
  • Gebicki J, Sysa-Jedrzejowska A, Adamus J, Wozniacka A, Rybak M, Zielonka J (2003) 1-Methylnicotinamide: a potent anti-inflammatory agent of vitamin origin. Pol J Pharmacol 55: 109-112.
  • Hassan N, Janjua MZ (2001) The optimum dose of nicotinamide for protection of pancreatic beta-cells against the cytotoxic effect of streptozotocin in albino rat. J Ayub Med Coll Abbottabad 13: 26-30.
  • Hoorens A, Pipeleers D (1999) Nicotinamide protects human beta cells against chemically-induced necrosis but not against cytokine-induced apoptosis. Diabetologia 42: 55-59.
  • Masutani M, Suzuki H, Kamada N, Watanabe M, Ueda O, Nozaki T, Jishage K, Watanabe T, Sugimoto T, Nakagama H, Ochiya T, Sugimura T (1999) Poly(ADP-ribose) polymerase gene disruption conferred mice resistant to streptozotocin-induced diabetes. Proc Natl Acad Sci USA 96: 2301-2304.
  • Pieper AA, Brat DJ, Krug DK, Watkins CC, Gupta A, Blackshaw S, Verma A, Wang ZQ, Snyder SH (1999) Poly(ADP-ribose) polymerase-deficient mice are protected from streptozotocin-induced diabetes. Proc Natl Acad Sci USA 96: 3059-3064.
  • Przygodzki T, Kazmierczak P, Sikora J, Watala C (2010) 1-methylnicotinamide effects on the selected markers of endothelial function inflammation and haemostasis in diabetic rats. Eur J Pharmacol 640: 157-162.
  • Slominska EM, Yuen A, Osman L, Gebicki J, Yacoub MH, Smolenski RT (2008) Cytoprotective effects of nicotinamide derivatives in endothelial cells. Nucleosides Nucleotides Nucleic Acids 27: 863-866.
  • Smolenski RT, Lachno DR, Ledingham SJ, Yacoub MH (1990) Determination of sixteen nucleotides nucleosides and bases using high-performance liquid chromatography and its application to the study of purine metabolism in hearts for transplantation. J Chromatogr 527: 414-420.
  • Uchigata Y, Yamamoto H, Kawamura A, Okamoto H (1982) Protection by superoxide dismutase catalase and poly(ADP-ribose) synthetase inhibitors against alloxan- and streptozotocin-induced islet DNA strand breaks and against the inhibition of proinsulin synthesis. J Biol Chem 257: 6084-6088.
  • Watala C, Kazmierczak P, Dobaczewski M, Przygodzki T, Bartus M, Lomnicka M, Slominska EM, Durackova Z, Chlopicki S (2009) Anti-diabetic effects of 1-methylnicotinamide (MNA) in streptozocin-induced diabetes in rats. Pharmacol Rep 61: 86-98.
  • Wozniacka A, Wieczorkowska M, Gebicki J, Sysa-Jedrzejowska A (2005) Topical application of 1-methylnicotinamide in the treatment of rosacea: a pilot study. Clin Exp Dermatol 30: 632-635.
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