Studies on meso-zeaxanthin for potential toxicity and mutagenicity

a b s t r a c t The purpose of these studies was to examine the potential toxicity and genotoxicity of meso-zeaxanthin (MZ). Toxicity was assessed by administering MZ daily to rats for 13 weeks followed by a 4-week recovery period. Potential genotoxicity was assessed in separate experiments using the Ames test method. Rats were randomly assigned to four groups to receive corn oil (control) or MZ at dose levels of 2, 20 and 200 mg/kg/day by oral gavage (10/sex/group). Additional rats (five of each sex) in the control and the 200 mg/kg/day groups were retained for the recovery period. No compound-related clinical, biochemical or pathological signs or symptoms were noted and the no-observed-adverse-effect-level (NOAEL) of MZ was >200 mg/kg/day. To investigate genotoxicity, MZ was tested for its ability to induce reverse mutations (±microsomal enzymes) at 2 genomic loci; the histidine locus of 4 strains of Salmonella typhimurium and the tryptophan locus of Escherichia coli strain WP2uvrA. Six doses of MZ ranging from 10 to 5000 lg/ plate were tested twice with vehicle and positive controls using 3 plates/dose. MZ did not cause any increase in the mean number of revertants/plate with any bacterial strain, with or without microsomal enzymes, and was therefore unlikely to be mutagenic

A Retrospective Investigation of Thiamin and Energy Intakes Following an Outbreak of Beriberi in the Gambia

In the early part of the rainy season in 1988, an outbreak of beriberi occurred in free-living adults in a relatively small area in the North Bank region of The Gambia. In 1995 we selected two compounds in a village called Chilla situated within the affected district to retrospectively examine dietary factors potentially contributing to the outbreak. There had previously been cases of beriberi in one compound (BBC) but not in the other (NBC). We measured energy and thiamin intakes for four days on six occasions during the year. We calculated energy and thiamin intakes of people living in the two compounds and foods were collected for thiamin analysis through the year. Thiamin:Energy ratios only met international recommendations in the immediate post‑harvest season when energy and thiamin intakes were highest and then fell through the year. In the rainy season when food was short and labour was heaviest, energy intakes were lower in the NBC but thiamin:energy ratios were lower in BBC. Records of rainfall in 1988 collected near the village indicated that the amount in August was twice the average. We suggest the heavy rainfall may have increased farm workload and reduced income from outside-village work activity. The lower energy intakes in the NBC may have forced adults to rest thus sparing thiamin demands and delaying onset of beriberi. In contrast, the higher energy intake of adults in the BBC may have enabled them to continue working, thus increasing demands for thiamin and inducing the earlier onset of beriberi

Comparison of LDL fatty acid and carotenoid concentrations and oxidative resistance of LDL in volunteers from countries with different rates of cardiovascular disease

Within Europe there are differences in cardiovascular disease (CVD) risk between countries and this might be related to dietary habits. Oxidative modification of LDL is suggested to increase the risk of CVD and both the fatty acid and antioxidant content of LDL can affect its oxidation. In the present study, concentration of LDL fatty acid and antioxidant micronutrients (tocopherols and carotenoids) and ex vivo oxidative resistance of LDL (lag phase) was compared in volunteers from five countries with different fruit and vegetable intakes and reported rates of CVD. Eighty volunteers (forty males, forty females per centre), age range 25-45 years, were recruited from France, Northern Ireland, UK, Republic of Ireland, The Netherlands, and Spain, and their LDL composition and lag phase were measured. There were some differences in LDL carotenoid and α-tocopherol concentrations between countries. α-Tocopherol was low and β- + γ-tocopherol were high (P<0·001) in the Dutch subjects. β-Carotene concentrations were significantly different between the French and Spanish volunteers, with French showing the highest and Spanish the lowest concentration. LDL lycopene was not different between centres in contrast to lutein, which was highest in French (twofold that in the Dutch and Spanish and threefold that in Northern Ireland and the Republic of Ireland, P<0·001). However absolute LDL saturated, monounsaturated, polyunsaturated and total unsaturated fatty acid concentrations were different between countries (P<0·001, total unsaturated highest in Northern Ireland) there was little difference in unsaturated:saturated fatty acid concentration ratios and no difference in polyunsaturated:saturated fatty acid concentration ratios. LDL from the Republic of Ireland (a region with a high rate of CVD) had greater resistance to Cu-stimulated oxidation than samples obtained from volunteers in other countries. In conclusion, LDL composition did not predict resistance to Cu-stimulated oxidation, nor is there evidence that LDL from volunteers in countries with lower rates of CVD have greater resistance to oxidatio

Adjusting plasma ferritin concentrations to remove the effects of subclinical inflammation in the assessment of iron deficiency: a meta-analysis

Background: The World Health Organization recommends serum ferritin concentrations as the best indicator of iron deficiency (ID). Unfortunately, ferritin increases with infections; hence, the prevalence of ID is underestimated. Objective: The objective was to estimate the increase in ferritin in 32 studies of apparently healthy persons by using 2 acute-phase proteins (APPs). C-reactive protein (CRP) and alpha(1)-acid glycoprotein (AGP), individually and in combination, and to calculate factors to remove the influence of inflammation from ferritin concentrations. Design: We estimated the increase in ferritin associated with inflammation (ie, CRP >5 mg/L and/or AGP >1 g/L). The 32 studies comprised infants (5 studies), children (7 studies), men (4 studies), and women (16 studies) (n = 8796 subjects). In 2-group analyses (either CRP or AGP), we compared the ratios of log ferritin with or without inflammation in 30 studies. In addition, in 22 studies, the data allowed a comparison of ratios of log ferritin between 4 subgroups: reference (no elevated APP), incubation (elevated CRP only), early convalescence (both APP and CRP elevated), and late convalescence (elevated AGP only). Results: In the 2-group analysis, inflammation increased ferritin by 49.6% (CRP) or 38.2% (AGP; both P <0.001). Elevated AGP was more common than CRP in young persons than in adults. In the 4-group analysis, ferritin was 30%, 90%, and 36% (all P < 0.001) higher in the incubation, early convalescence, and late convalescence subgroups, respectively, with corresponding correction factors of 0.77, 0.53, and 0.75. Overall, inflammation increased ferritin by approximate to 30% and was associated with a 14% (CI: 7%, 21%) underestimation of ID. Conclusions: Measures of both APP and CRP are needed to estimate the full effect of inflammation and can be used to correct ferritin concentrations. Few differences were observed between age and sex subgroups. Am J Clin Nutr 2010;92:546-55

Human malarial disease: a consequence of inflammatory cytokine release

Malaria causes an acute systemic human disease that bears many similarities, both clinically and mechanistically, to those caused by bacteria, rickettsia, and viruses. Over the past few decades, a literature has emerged that argues for most of the pathology seen in all of these infectious diseases being explained by activation of the inflammatory system, with the balance between the pro and anti-inflammatory cytokines being tipped towards the onset of systemic inflammation. Although not often expressed in energy terms, there is, when reduced to biochemical essentials, wide agreement that infection with falciparum malaria is often fatal because mitochondria are unable to generate enough ATP to maintain normal cellular function. Most, however, would contend that this largely occurs because sequestered parasitized red cells prevent sufficient oxygen getting to where it is needed. This review considers the evidence that an equally or more important way ATP deficency arises in malaria, as well as these other infectious diseases, is an inability of mitochondria, through the effects of inflammatory cytokines on their function, to utilise available oxygen. This activity of these cytokines, plus their capacity to control the pathways through which oxygen supply to mitochondria are restricted (particularly through directing sequestration and driving anaemia), combine to make falciparum malaria primarily an inflammatory cytokine-driven disease