Nicotinamide reduces hypoxic ischemic brain injury in the newborn rat

Abstract

Nicotinamide reduces ischemic brain injury in adult rats. Can similar brain protection be seen in newborn animals? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of 8% oxygen. Nicotinamide 250 or 500 mg/kg was administered i.p. 5 min after reoxygenation, with a second dose given at 6 h after the first. Brain damage was evaluated by weight deficit of the right hemisphere at 22 days following hypoxia. Nicotinamide 500 mg/kg reduced brain weight loss from 24.6 ± 3.6% in vehicle pups (n = 28) to 11.9 ± 2.6% in the treated pups (n = 29, P < 0.01), but treatment with 250 mg/kg did not affect brain weight. Nicotinamide 500 mg/kg also improved behavior in rotarod performance. Levels of 8-isoprostaglandin F 2α measured in the cortex by enzyme immune assay 16 h after reoxygenation was 115 ± 7 pg/g in the shams (n = 6), 175 ± 17 pg/g in the 500 mg/kg nicotinamide treated (n = 7), and 320 ± 79 pg/g in the vehicle treated pups (n = 7, P < 0.05 versus sham, P < 0.05 versus nicotinamide). Nicotinamide reduced the increase in caspase-3 activity caused by hypoxic ischemia (P < 0.01). Nicotinamide reduces brain injury in the neonatal rat, possibly by reducing oxidative stress and caspase-3 activity.

Therapeutic Potential of 1-Methylnicotinamide against Acute Gastric Lesions Induced by Stress: Role of Endogenous Prostacyclin and Sensory Nerves

“…than that exerted by NA, a biological precursor of MNA. With respect to NA, this activity, in keeping with the previous observation that NA has been originally recognized as an important cofactor for the formation of dinucleotide, exhibits anti-inflammatory and radical scavenging activity (Ogata et al, 2002) and affords neuroprotection against hypoxic brain injury and thermal and spinal cord damage (Smith et al, 1989;Feng et al, 2006). Moreover, the activation of adenylyl cyclase/protein kinase A system facilitates a neural release of NA adenine dinucleotide in the mesenteric artery system, suggesting the role for derivatives of NA, in the control of the vascular circulation in the upper gastrointestinal tract (Bobalova and Mutafova-Yambolieva, 2006).…”

NAD+and Vitamin B3: From Metabolism to Therapies

“…When assessed for behavior, offspring whose mothers were administered nicotinamide performed better in a number of tests for anxiety, a typical side effect of fetal alcohol syndrome in mice, than their nicotinamide-untreated controls (Ieraci and Herrera, 2006). Likewise, in fetal ischemia, nicotinamide treatment has been shown to prevent neural damage versus untreated controls, suggesting that nicotinamide could represent a reasonable intervention for early neuron damage during development (Feng et al, 2006).…”

Erythropoietin: Elucidating new cellular targets that broaden therapeutic strategies

“…Reactive oxygen species can involve superoxide free radicals, hydrogen peroxide, singlet oxygen, nitric oxide (NO), and peroxynitrite (Chong et al, 2005e). Most species are produced at low levels during normal physiological conditions and are scavenged by endogenous antioxidant systems that include superoxide dismutase (SOD), glutathione peroxidase, catalase, and small molecule substances such as vitamins C and E. Other closely linked pathways to oxidative stress may be tempered by different vitamins, such as vitamin D 3 (Regulska et al, 2007) and the amide form of niacin or vitamin B 3 , nicotinamide (Chlopicki et al, 2007;Chong et al, 2002d;Feng et al, 2006;Hara et al, 2007;Ieraci and Herrera, 2006;Lin et al, 2000;.…”