X-Message-Number: 11690 Date: Thu, 06 May 1999 15:01:17 -0700 From: Olaf Henny <> Subject: PBN May Have Use in Restoring Ischemic Damage A posting by Peter H. Proctor in sci.life-extension, which told of extension of mean and maximum lifspan in mice after adding PBN to their drinking water prompted me to look it up in Medline. A couple of abstracts sprang up, that indicated, that PBN may have a use in reducing some ischemic damage, as well as restoring some mitochondrial function if administered in conjunction with acetyl-L-carnitine. Best, Olaf N-tert-Butyl-alpha-phenylnitrone [3376-24-7] Synonyms: Phenyl N-tert-butylnitrone; PBN; 2-Propanamine, 2-methyl-N-(phenylmethylene)-, N-oxide C11H15NO 177.25 N-tert-butyl-alpha-phenylnitrone reduces the number of microinfarctions in the rabbit brain cortex. Roos MW, Ericsson A Department of Physiology, BMC, Uppsala University, Sweden. Dementia due to cerebral ischemic lesions is relatively common in the elderly. Since many of these lesions are probably caused by emboli, studying emboli-induced cerebral lesions in rabbits should, hopefully, provide information that is useful when searching for a means of preventing and treating vascular dementia in humans. Using magnetic resonance imaging we have found that N-tert-butyl-alpha-phenyl-nitrone (a free radical scavenger) reduced the number of emboli-induced cerebral microinfarctions in the rabbit cortex but did not have any impact on the number of infarctions found in the subcortical structures. The results suggest that significant amount of free radicals are produced in the ischemic foci located in the cortex, but not in the ischemic foci located in the subcortical structures. This finding may be of importance when considering treatments for cerebral ischemia in humans. PMID: 9928850, UI: 99125930 Hagen TM, Wehr CM, Ames BN Department of Molecular and Cell Biology, University of California at Berkeley 94720, USA. We show that mitochondrial function in the majority of hepatocytes isolated from old rats (24 mo) is significantly impaired. Mitochondrial membrane potential, cardiolipin levels, respiratory control ratio, and overall cellular O2 consumption decline, and the level of oxidants increases. To examine whether dietary supplementation of micronutrients that may have become essential with age could reverse the decline in mitochondrial function, we supplemented the diet of old rats with 1% (w/v) acetyl-L-carnitine (ALCAR) in drinking water. ALCAR supplementation (1 month) resulted in significant increases in cellular respiration, mitochondrial membrane potential, and cardiolipin values. However, supplementation also increased the rate of oxidant production, indicating that the efficiency of mitochondrial electron transport had not improved. To counteract the potential increase in oxidative stress, animals were administered N-tert-butyl-alpha-phenyl-nitrone (30 mg/kg) (PBN) with or without ALCAR. Results showed that PBN significantly lowered oxidant production as measured by 2,7'-dichlorofluorescin diacetate (DCFH), even when ALCAR was coadministered to the animals. Thus, dietary supplementation with ALCAR, particularly in combination with PBN, improves mitochondrial function without a significant increase in oxidative stress. PMID: 9928432, UI: 99127393 Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=11690