Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease.

Nicotinamide adenine dinucleotide (NAD+) supplies energy for deoxidation and anti-inflammatory reactions fostering the production of adenosine triphosphate (ATP). The kidney is an essential regulator of body fluids through the excretion of numerous metabolites. Chronic kidney disease (CKD) leads to the accumulation of uremic toxins, which induces chronic inflammation. In this study, the role of NAD+ in kidney disease was investigated through the supplementation of nicotinamide (Nam), a precursor of NAD+, to an adenine-induced CKD mouse model. Nam supplementation reduced kidney inflammation and fibrosis and, therefore, prevented the progression of kidney disease. Notably, Nam supplementation also attenuated the accumulation of glycolysis and Krebs cycle metabolites that occurs in renal failure. These effects were due to increased NAD+ supply, which accelerated NAD+-consuming metabolic pathways. Our study suggests that Nam administration may be a novel therapeutic approach for CKD prevention.

Lack of Endothelial Nitric Oxide Synthase Accelerates Ectopic Calcification in Uremic Mice Fed an Adenine and High Phosphorus Diet.

Ectopic calcification is a risk of cardiovascular disease in chronic kidney disease (CKD) patients, and impaired endothelial nitric oxide synthase (eNOS) is involved in the CKD complications. However, whether eNOS dysfunction is a cause of ectopic calcification in CKD remains to be elucidated. To address this issue, we investigated the role of eNOS in ectopic calcification in mice with renal injury caused by an adenine and high-phosphorus (Ade + HP) diet. DBA/2J mice, a calcification-sensitive strain, were fed Ade + HP for 3 weeks. Expression levels of eNOS-related genes were reduced significantly in their calcified aorta. C57BL/6J is a calcification-resistant strain, and wild-type mice showed mild calcified lesions in the aorta and kidney when given an Ade + HP diet for 4 weeks. In contrast, a lack of eNOS led to the development of severe aortic calcification accompanied by an increase in runt-related transcription factor 2, an osteochondrogenic marker. Increased renal calcium deposition and the tubular injury score were remarkable in mice lacking eNOS-fed Ade + HP. Exacerbation of ectopic calcification by a lack of eNOS is associated with increased oxidative stress markers such as nicotinamide adenine dinucleotide phosphate oxidases. In conclusion, eNOS is critically important in preventing ectopic calcification. Therefore, the maintenance of eNOS is useful to reduce cardiovascular disease events and to improve prognosis in CKD patients.

Inhibitory effect of cranberry polyphenol on cariogenic bacteria.

The purpose of this study was to investigate the effect of cranberry polyphenol fraction on mutans streptococci. Hydrophobicity is an important factor in the adherence of bacteria to the tooth surface. We found that cranberry polyphenol fraction significantly decreased the hydrophobicity of Streptococcus sobrinus 6715, Streptococcus mutans MT8148R and JC2 in a dose-dependent manner (p<0.05). Biofilm formation by S. sobrinus 6715 and S. mutans MT8148R was inhibited by 100 microg/ml cranberry polyphenol fraction (p<0.01). When dosage was increased to 500 microg/ml, biofilm formation by S. mutans JC2 was significantly inhibited (p<0.05). Addition of 500 microg/ml cranberry polyphenol fraction to medium inhibited growth of S. mutans MT8148R compared with the control (p<0.05).

Antioxidant properties of aqueous extracts from red tide plankton cultures.

The antioxidant properties of aqueous extracts from the dinophycean flagellates Gymnodinium impudicum and Alexandrium affine and the raphidophycean flagellate Chattonella ovata were examined. An electron spin resonance (ESR)-spin trapping method coupled with steady state kinetic analysis showed that all of the extracts directly scavenge superoxide, and that the superoxide scavenging potential of any of the extracts was comparable to that of L-ascorbic acid. As for hydroxyl radical scavenging, the Fenton reaction and the method of ultraviolet radiation to hydrogen peroxide were used as hydroxyl radical generation systems. All of extracts reduced the level of hydroxyl radicals in both of the systems, indicating that the extracts also directly scavenge hydroxyl radicals. Since the levels of phenolic compounds did not correlate with the antioxidant activities of the extracts, substances other than phenolic compounds also appeared to be attributable to the activities. It is of our interest that the scavenging activities of extract from G. impudicum against superoxide and hydroxyl radicals were increased by heat exposure at 100 degrees C and 200 degrees C respectively. Although the reason for the increased activities of the aqueous extract from G. impudicum is not clear, the heat-resistance of the extract from G. impudicum might make it a desirable antioxidant.

Increased anti-oxidative potency of garlic by spontaneous short-term fermentation.

Fundamental anti-oxidative properties of 80% ethanol extract from garlic fermented for the relatively short period of time (40 days at 60-70 degrees C, 85-95% relative humidity) were examined. Superoxide dismutase (SOD)-like activity, scavenging activity against hydrogen peroxide and the polyphenol content of the garlic extract were increased 13-folds, more than 10-folds, and 7-folds, respectively, as compared with those of the control garlic extract. The results indicate that relatively short-term spontaneous fermentation potentiates anti-oxidative properties of garlic in fresh form, which is, at least in part, attributable to the increased level of polyphenols. Since superoxide is the primary upstream radical of the chain reaction with reactive oxygen species and hydrogen peroxide is generated from the scavenging reaction by SOD, the fermented- garlic is suggested to possess desirable anti-oxidative properties.

Increased level of tetrahydro-beta-carboline derivatives in short-term fermented garlic.

In our previous study [1], we found that relatively short-term spontaneous fermentation (40 days at 60-70 degrees C, 85-95% relative humidity) potentiates anti-oxidative properties of garlic, in which scavenging activity against hydrogen peroxide was included. Since tetrahydro-beta-carboline derivatives (THbetaCs) that possess hydrogen peroxide scavenging activity have recently been identified in aged garlic extract, THbetaCs were quantitatively analyzed with liquid chromatography-mass spectrometry (LC-MS). (1R, 3S)-1-Methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCC) and (1S, 3S)-MTCC were found in the fermented garlic extract whereas only trace levels of MTCCs were detected in the row garlic extract. Therefore, it is suggested that relatively short-term fermentation potentiates scavenging activity of garlic against hydrogen peroxide by forming THbetaCs, especially MTCCs.