Nicotinamide reduces inflammation and oxidative stress via the cholinergic system in fructose-induced metabolic syndrome in rats.

AIMS: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have been associated with risk factors for metabolic syndrome (MetS). Our objective was to evaluate the effect of nicotinamide (NAM) on the activities, expression and protein content of cholinesterases in a MetS model. MAIN METHODS: MetS was induced in male rats administrating 40% fructose to the drinking water for 16 weeks. Additionally, from 5th week onward, the carbohydrate solution was replaced by NAM, at several concentrations for 5 h each morning for the next 12 weeks. In the 15th week, the glucose tolerance test was conducted, and blood pressure was measured. After the treatment period had concluded, the biochemical profile; oxidant stress; proinflammatory markers; and the activity, quantity and expression of cholinesterases were evaluated, and molecular docking analysis was performed. KEY FINDINGS: The MetS group showed anthropometric, hemodynamic and biochemical alterations and increased cholinesterase activity, inflammation and stress markers. In the liver, cholinesterase activity and mRNA, free fatty acid, tumor necrosis factor-alpha (TNF-α), and thiobarbituric acid-reactive substance (TBARS) levels were increased, while reduced glutathione (GSH) levels were decreased. NAM partially or totally decreased risk factors for MetS, markers of stress and inflammation, and the activity (serum and liver) and expression (liver) of cholinesterases. Molecular docking analysis showed that NAM has a greater affinity for cholinesterases than acetylcholine (ACh), suggesting NAM as an inhibitor of cholinesterases. SIGNIFICANCE: Supplementation with 40% fructose induced MetS, which increased the activity and expression of cholinesterases, oxidative stress and the inflammation. NAM attenuated these MetS-induced alterations and changes in cholinesterases.

High fructose-containing drinking water-induced steatohepatitis in rats is prevented by the nicotinamide-mediated modulation of redox homeostasis and NADPH-producing enzymes.

An imbalance in the redox state, increased levels of lipid precursors and overactivation of de novo lipogenesis determine the development of fibrosis during nonalcoholic steatohepatitis (NASH). We evaluated the modulation of NADPH-producing enzymes associated with the antifibrotic, antioxidant and antilipemic effects of nicotinamide (NAM) in a model of NASH induced by excess fructose consumption. Male rats were provided drinking water containing 40% fructose for 16 weeks. During the last 12 weeks of fructose administration, water containing NAM was provided to some of the rats for 5 h/day. The biochemical profiles and the ghrelin, leptin, lipoperoxidation and TNF-α levels in serum and the glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME) and NADP+-dependent isocitric dehydrogenase (IDP) levels, the reduced/oxidized glutathione (GSH/GSSG) and reduced/oxidized nicotinamide adenine dinucleotide (phosphate) (NAD(P)H/NAD(P)+) ratios, and the levels of various lipogenic and fibrotic markers in the liver were evaluated. The results showed that hepatic fibrosis induced by fructose consumption was associated with weight gain, hunger-satiety system dysregulation, hyperinsulinemia, dyslipidemia, lipoperoxidation and inflammation. Moreover, increased levels of hepatic G6PD and ME activity and expression, the NAD(P)H/NAD(P)+ ratios, and GSSG concentration and increased expression of lipogenic and fibrotic markers were detected, and these alterations were attenuated by NAM administration. Specifically, NAM diminished the activity and expression of G6PD and ME, and this effect was associated with a decrease in the NADPH/NADP+ ratios, increased GSH levels and decreased lipoperoxidation and inflammation, ameliorating fibrosis and NASH development. NAM reduces liver steatosis and fibrosis by regulating redox homeostasis through a G6PD- and ME-dependent mechanism.

Prevalence of serological markers against measles, rubella, varicella, hepatitis B, hepatitis C, and human immunodeficiency virus among medical residents in Mexico.

BACKGROUND: Vaccination programs among health care workers are based on seroprevalence studies, which seldom include medical residents or students. The objective of this study was to determine the seroprevalence of antibodies against measles, rubella, varicella, hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency virus (HIV) among medical residents. METHODS: This study was designed as a prospective survey. A self-reported questionnaire was used to obtain the information. Serum samples were tested for antibodies by commercial immunoenzymatic assays. Statistical analysis was descriptive; history of exposure was evaluated as a diagnostic test and sensitivity, specificity, and predictive values were calculated according to Bayes theorem. RESULTS: Eighty-nine residents were included, the median age was 27 years, and 58 (65.2%) were female. Seventy-two (79.7%) had been vaccinated against HBV, but vaccination was complete in only 30/72 (41.6%). All were positive for measles and varicella, with the exception of one case for each. The serology for rubella was negative in 12 residents (10 women). Three residents had anti-core against HBV, with negative surface antigen. One positive case for HCV was confirmed by Western blot. All were negative for HIV. A history of prior varicella had a 100% positive predictive value; in contrast, the negative predictive value was quite low (7%). CONCLUSIONS: Negative serology for rubella among women and incomplete vaccination against HBV support the implementation of vaccination programs in medical schools in Mexico.

Susceptibility to varicella-zoster infection in individuals 1 to 29 years of age in Mexico.

BACKGROUND: The prevalence of varicella zoster virus (VZV) infection has been poorly studied in Latin America. The aim of this work was to study the seroprevalence of antibody to VZV infection in Mexico. Infection was determined in 3,737 individuals. METHODS: Samples were collected during a national serologic survey performed during 1987-1988 and represented individuals 1- to 29-years-old from all socioeconomic levels and from rural and urban communities throughout the country. Antibodies anti-VZV were measured with a commercially available enzyme-linked immunosorbent assay (VARELISA Merck, Germany). RESULTS: In the population studied, 464 individuals (12.4%) were seronegative or susceptible to infection, whereas about 17.0% of individuals 1- to 19-years-old were susceptible to infection. Between the ages of 20 to 24 years, 8.4% were susceptible and between 25 to 29 years, 5.0% of persons were still susceptible to infection. CONCLUSIONS: Socioeconomic level, density of population, crowding, and gender were not found as risk factors for susceptibility to VZV infection in adolescents and young adults. Low educational level was found as a risk factor for susceptibility. High proportions of adolescents and young adults in Mexico are susceptible to VZV infection and should receive special attention when designing vaccination programs.