title: Effects of 1-methylnicotinamide and its metabolite N-methyl-2-pyridone-5-carboxamide on streptozotocin-induced toxicity in murine insulinoma MIN6 cell line.
abstract: 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.
authors.affiliation: Department of Haemostasis and Haemostatic Disorders, Chair of Laboratory Diagnostics, Medical University of Lodz, University Clinical Hospital No. 2, Łódź, Poland. tomasz.przygodzki@umed.lodz.pl
authors.forename: Tomasz
authors.initials: T
authors.lastname: Przygodzki
authors.forename: Ewa
authors.initials: E
authors.lastname: Slominska
authors.forename: Ewa
authors.initials: E
authors.lastname: Polakowska
authors.forename: Wojciech
authors.initials: W
authors.lastname: Mlynarski
authors.forename: Cezary
authors.initials: C
authors.lastname: Watala
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D007340:Insulinoma / Q000378:metabolism*; D051379:Mice; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology*; D013311:Streptozocin / Q000494:pharmacology*
chemical_list: C525085:N-methyl-2-pyridone-5-carboxamide; D011728:Pyridones; D009243:NAD; D009536:Niacinamide; D013311:Streptozocin; D000255:Adenosine Triphosphate; C024058:N(1)-methylnicotinamide