Pharmacology. 2003 Nov;69(3):150-7. Klaidman L, Morales M, Kem S, Yang J, Chang ML, Adams Jr JD. USC School of Pharmacy, Los Angeles, Calif., USA.
The purpose of the current study was to investigate aspects of improved bioenergetic function using nicotinamide during stroke. Using a global ischemia-reperfusion mouse model, ATP was depleted by 50% in the brain. The use of nicotinamide to provide a large reserve of brain NAD(+) restored ATP levels to 61% of control levels.
Alternatively, using nicotinamide as a PARP inhibitor restored ATP levels up to 72%. However, using a large reserve of NAD(+) in the brain together with PARP inhibition proved to be additive, restoring ATP to 85% of control levels during the first critical 5 min of reperfusion. NAD(+) and ATP levels correlated almost exactly. Brain mitochondrial function was also examined after cerebral ischemia-reperfusion. State 3 respiration of complex I was found to be abolished. However, this was a non-permanent inhibition of activity in vitro, since (NADH ubiquinone oxideroductase) complex I activity in these mitochondria was restored upon the addition of NADH. In vivo, the use of increased brain NAD(+) and PARP inhibition was able to partially restore mitochondrial respiration.
Taken together, the results show that nicotinamide offers a substantial protective role in terms of preservation of cellular ATP and mitochondrial NAD-linked respiration. Copyright 2003 S. Karger AG, Basel
PMID: 14512702 [PubMed – in process]