Regional differences in microsomal lipid peroxidation and antioxidant levels in the guinea pig adrenal cortex

Lipid peroxidation (LP) and antioxidant levels were studied in the chromatically distinct inner (zona reticularis) and outer (zona fasciculata + zona glomerulosa) zones of the guinea pig adrenal cortex. Ferrous ion (Fe2+) produced a concentration-dependent (10(-5) to 10(-3) M) stimulation of microsomal LP in both zones, but LP, as estimated by malonaldehyde production, was far greater in the inner zone. Although cytosolic ascorbic acid content was similar in the two zones, microsomal tocopherol levels were approx 4 times greater in the outer than inner zone. Subphysiological concentrations of ascorbic acid, like Fe2+, initiated LP to a greater extent in inner than outer zone microsomes; optimal stimulation of LP by ascorbic acid occurred at concentrations of 100-200 microM in both zones. Physiological concentrations of ascorbic acid (1-5 mM), by contrast, did not initiate LP and, in fact, markedly inhibited Fe2+-induced LP in both inner and outer zone microsomal preparations. Outer zone microsomes were more sensitive to the antioxidant effects of ascorbic acid than were inner zone preparations. Addition of alpha-tocopherol to inner zone microsomal suspensions inhibited Fe2+-induced LP. The results indicate that there are regional differences in adrenocortical LP which may be caused by differences in tocopherol content. alpha-Tocopherol may serve important antioxidant functions within the adrenal cortex, thereby contributing to the functional zonation of the gland.     

Influence of classification levels of ram sexual activity on spring breeding ewes

Ram lambs (7–8 months old) and mature rams (19–20 months old) were used to evaluate the effect of classification levels of male sexual performance on reproductive performance of ewes during spring breeding. In Exp. 1, sexually active ram lambs with high (1.8±0.3; n=5) and low (0.9±0.2; n=5) sexual performance scores (HP and LP; mean±S.E.M.) were used in single sire breeding pens. Ewes (n=305) were stratified by age and assigned to 10 pens for 34 days starting in late March. For Exps. 2 and 3, two replicates were conducted for 2 years with sexually active mature rams in a single sire mating scheme. For Exp. 2, HP rams (n=5) averaged 3.6±0.2 ejaculations and LP rams (n=7) 1.8±0.2 ejaculations for sexual performance scores based on nine, 30 min serving capacity tests (SCT). Polypay ewes (n=152 to 153 per year) were stratified by age and assigned to pens each year for 34–38 days starting in late March for years 1 and 2. For Exp. 3, HP rams (n=6) averaged 3.7±0.1 ejaculations and LP rams (n=10) 2.3±0.1 ejaculations for sexual performance scores based on 18, 30 min SCT. Polypay ewes (n=229 in year 3 and n=244 in year 4) were stratified by age and assigned to pens each year for 34 days starting in late March. In Exp. 1, lambing rates for ewes bred to HP versus LP ram lambs did not differ (65.8 versus 53.0; P=0.20). Prolificacy tended (P=0.06) to be increased by 0.1 lambs in ewes bred by LP ram lambs. Total number of lambs born per ewe present at lambing, and lambing distribution were not altered by HP and LP ram lambs. In Exp. 2, lambing rates for fall-lambing ewes bred to mature HP or LP rams did not differ (58.1 versus 60.1; P=0.78). In Exp. 3, lambing rates for fall-lambing ewes bred to mature HP or LP rams did not differ (74.3 versus 69.0; P=0.35). There was no difference (P>0.10) between years for Exp. 2 or Exp. 3, and mature HP and LP rams did not affect the other reproductive variables monitored. Analyses of the combined data for Exps. 2 and 3 indicated only a year difference (P<0.001) in lambing rates and total lambs born. Present studies indicate that different sexual performance classifications for ram lambs and mature rams did not alter lambing rates or distribution of lambing of Polypays bred in late March to April. These results indicate that HP and LP, sexually active, Polypay rams and ram lambs with average to high quality semen can provide a source of rams for spring breeding Polypays in ambient conditions and that there was no advantage to using HP over sexually active LP ram lambs or rams.     

Plasma Ascorbic Acid,A Priori Diet Quality Score,and Incident Hypertension: A Prospective Cohort Study

Vitamin C may reduce risk of hypertension, either in itself or by marking a healthy diet pattern. We assessed whether plasma ascorbic acid and the a priori diet quality score relate to incident hypertension and whether they explain each other’s predictive abilities. Data were from 2884 black and white adults (43% black, mean age 35 years) initially hypertension-free in the Coronary Artery Risk Development in Young Adults Study (study year 10, 1995–1996). Plasma ascorbic acid was assessed at year 10 and the diet quality score at year 7. Eight-hundred-and-forty cases of hypertension were documented between years 10 and 25. After multiple adjustments, each 12-point (1 SD) higher diet quality score at year 7 related to mean 3.7 μmol/L (95% CI 2.9 to 4.6) higher plasma ascorbic acid at year 10. In separate multiple-adjusted Cox regression models, the hazard ratio of hypertension per 19.6-μmol/L (1 SD) higher ascorbic acid was 0.85 (95% CI 0.79–0.92) and per 12-points higher diet score 0.86 (95% CI 0.79–0.94). These hazard ratios changed little with mutual adjustment of ascorbic acid and diet quality score for each other, or when adjusted for anthropometric variables, diabetes, and systolic blood pressure at year 10. Intake of dietary vitamin C and several food groups high in vitamin C content were inversely related to hypertension, whereas supplemental vitamin C was not. In conclusion, plasma ascorbic acid and the a priori diet quality score independently predict hypertension. This suggests that hypertension risk is reduced by improving overall diet quality and/or vitamin C status. The inverse association seen for dietary but not for supplemental vitamin C suggests that vitamin C status is preferably improved by eating foods rich in vitamin C, in addition to not smoking and other dietary habits that prevent ascorbic acid from depletion.     

Topographical localization of lipofuscin pigment in the brain of the aged fat‐tailed dwarf lemur (Cheirogaleus Medius) and grey lesser mouse lemur (Microcebus Murinus): Comparison to iron localization

The present study was undertaken to explore the distribution of lipofuscin in the brain of cheirogaleids by autofluorescence and compare it to other studies of iron distribution. Aged dwarf (Cheirogaleus medius) and mouse (Microcebus murinus) lemurs provide a reliable model for the study of normal and pathological cerebral aging. Accumulation of lipofuscin, an age pigment derived by lipid peroxidation, constitutes the most reliable cytological change correlated with neuronal aging. Brain sections of four aged (8–15 year old) and 3 young (2–3 year old) animals were examined. Lipofuscin accumulation was observed in the aged animals but not in the young ones. Affected regions include the hippocampus (granular and pyramidal cells), where no iron accumulation was observed, the olfactory nucleus and the olfactory bulb (mitral cells), the basal forebrain, the hypothalamus, the cerebellum (Purkinje cells), the neocortex (essentially in the pyramidal cells), and the brainstem. Even though iron is known to catalyse lipid oxidation, our data indicate that iron deposits and lipofuscin accumulation are not coincident. Different biochemical and morphological cellular compartments might be involved in iron and lipofuscin deposition. The nonuniform distribution of lipofuscin indicates that brain structures are not equally sensitive to the factors causing lipofuscin accumulation. The small size, the rapid maturity, and the relatively short life expectancy of the cheirogaleids make them a good model system in which to investigate the mechanisms of lipofuscinogenesis in primates. Am. J. Primatol. 49:183–193, 1999. © 1999 Wiley‐Liss, Inc.     

Ascorbic acid and aging in the rat. Uptake of ascorbic acid by teeth and concentration of various forms of ascorbic acid in different organs

1. The uptake of ascorbic acid in vitro by the teeth of rats showed a gradual decrease with age, indicating that the uptake may be related to collagen synthesis as in bone. 2. The concentration of total free ascorbic acid in various organs declined with age, but the rate of decline was different in different organs. In the spleen, however, it increased until maturity and then declined. 3. This decrease may be due to one or both of the following reasons: (a) the permeability of different tissues may decrease at different rates for ascorbic acid, or (b) the requirement for ascorbic acid may decrease at different rates. 4. The bound ascorbic acid declined with age in the skin, kidney, liver and brain after the age of 10-12 weeks, and in the spleen after the age of 26 weeks. 5. The concentration of dehydroascorbic acid and dioxogulonic acid declined with age in the skin.     

Concentrations of catecholamines, ascorbic acid, progesterone and oxytocin in the corpora lutea of cyclic and pregnant cattle.

To determine if there are inter-relationships between progesterone, oxytocin (OT), dopamine (DA), noradrenaline (NA) and ascorbic acid, these compounds were measured in the corpus luteum (CL) from cattle at different stages of the oestrous cycle (n = 42) and from 1-5 months of pregnancy (n = 27). They were measured by radioimmunoassay (RIA), high performance liquid chromatography (HPLC) and colorimetric methods. Corpora lutea were collected from heifers and cows within 30 min of slaughter on days 1-5, 6-10, 11-16 and 17-21 of the oestrous cycle. The stage of pregnancy was determined on the basis of foetal size and development. Each CL was divided into four parts and stored in liquid nitrogen. For hormone estimation, the tissue was homogenised/powdered and suspended in phosphate buffer (for OT and progesterone), 0.1 M trichloracetic acid (TCA; for catecholamines) or in ice-cold metaphosphoric acid (for ascorbic acid). There were no significant differences in the measured parameters between cows and heifers, and so the data were combined. The concentration of DA was correlated with NA (r = 0.66; P < 0.001) during the oestrous cycle and was highest in newly formed CL (P < 0.01) as compared with early CL, regressed CL and CL of pregnant females. NA was negatively correlated (P < 0.01) with progesterone (r = -0.53) and OT (r = -0.41). In contrast, progesterone and OT were positively correlated with each other (r = 0.81; P < 0.01) during all stages of the oestrous cycle, but not during pregnancy. The lowest concentrations of ascorbic acid were observed in regressed CL. Ascorbic acid concentrations were correlated (P < 0.01) with those of progesterone (r = 0.68), OT (r = 0.42) and DA (r = -0.37). Luteal concentrations of ascorbic acid, progesterone and OT followed a pattern consistent with the development and regression of the CL. Luteal concentrations of catecholamines were not consistent with this pattern.     

Lectin histochemical study of lipopigments with special regard to neuronal ceroid-lipofuscinosis

Summary Concanavalin A (ConA) binding to lipopigments (LPs) of the lipofuscin type was proved to be due to the high content of mannose. The nature of the mannose bearing compound was twofold. One part was soluble in modified chloroform-methanol-water mixture (10:10:3) corresponding possibly to the oligosaccharyl diphosphodolichol (oligo-PP-Dol) described to be increased in LPs especially of inherited types. The second part, most probably a glycoprotein (GP), was entirely resistant to various extraction procedures. The ratio of the two components varied. The deposition of the typical lipofuscin (age pigment) was dominated by the GP component. Its amount was greatest in neurolipofuscin (especially in the olivary nucleus) and in the myocardium but very little in hepatocytic lipofuscin. In human neuronal ceroid lipofuscinoses (of early juvenile, and juvenile types) both components were found in large quantities in the storage granules of the affected neurons. The protein type variant of the storage material (Elleder 1978) displayed the highest degree of lipid-bound mannose accumulation, the GP component being extremely low or entirely absent. In the late infantile, infantile and Kufs variants studied in paraffin sections only, the GP component was detetable, too as in the case of the secondary neuronal LP in mucopolysaccharidoses and gangliosidoses. In the dog model of NCL lipid bound mannose clearly predominated, the GP component being concentrated in the cytoplasm and on the periphery od some storage granules. The nature of the GP component, a new finding of LP analysis, is discussed. The metabolic relationship between the two components is uncertain. Neither could be identified as the component resposible for autofluorescence. However, both are most probably responsible for PAS positivity of lipofuscins. The ceroid-type histiocytic LP did not display any detectable increase in any of the mannose bearing components.Abbreviations NCL neuronal ceroid lipofuscinosis - HNCL human NCL - CNCL canine NCL - ONCL ovine NCL - LP lipopigment - GP glycoprotein     

Evaluation and correction of the vitamin C status in relation to the problem of the experimental modification of long-term radiation effects]

A lognormal double-peak pattern of ascorbic acid content distribution within rat daily urine and the presence in the population of vitamin C hypo-, hyper-, and normally producing individuals have been established. Radiation-induced changes in the C-vitamin status of rats during their lifetime were assessed by average geometrical levels of acid excretion. A 1.5-3-fold decrease in providing vitamin C producing animals with vitamin C was demonstrated a year after intrapulmonary incorporation of 239PuO2.     

Changes in hydrophilic antioxidant activity in Avena sativa and Triticum aestivum leaves of different age during de-etiolation and high-light treatment

The steady-state of reactive oxygen species (ROS) in plant cells is controlled by ROS-producing and scavenging agents. A large cellular pool of antioxidant metabolites is involved in their control. Variations in this antioxidant pool may be monitored by measuring changes in hydrophilic antioxidant activity (free radical-quenching activity of water-soluble components) and ascorbic acid levels. The de-etiolation process and induction of light stress in Avena sativa and Triticum aestivum leaves were used as physiological models to study the antioxidant status at different ages. The data showed that five-day-old green plants and de-etiolated plants of the same age have similar hydrophilic antioxidant activity (8 mol ASC equivalents g FW^–1), which increases during the de-etiolation process. In oat and wheat, young leaves (five days old) had higher antioxidant status (hydrophilic antioxidant activity and ascorbic acid level) than old leaves (10 and 20 days old). High-light treatment caused a decrease in antioxidant status, especially in young leaves. Hydrophilic antioxidant activity and ascorbic acid levels recovered totally or partially after 30 or 60 min in the dark. This capacity also depends on age and species. The ascorbic acid/hydrophilic antioxidant activity ratio is presented as an indicator of antioxidant variations in response to stress, but taking into account the absolute levels of antioxidants.     

The effect of dietary antioxidants on lipofuscin accumulation in the crustacean brain

Lipofuscin accumulation is associated with ageing at the subcellular level. A strong correlation between lipofuscin and age has been found in crustaceans using histological techniques. This association has been proposed as the basis for a methodology to age crustaceans and in some cases lipofuscin levels were found to be better correlated with age than size. The experiment presented here was designed to test the potential effect of diet, in particular dietary antioxidants, on lipofuscin accumulation and age estimation.The shrimp, Penaeus japonicus, was reared in an aquaculture facility and fed commercial pellets with modified vitamins C and E contents. One group was fed with levels of vitamins C and E of 1000 and 150 mg/kg, respectively, and another group with 2500 and 5000 mg/kg, respectively. The experiment started when the shrimp were 19 weeks old. Samples were obtained at this point and at ages 33 and 43 weeks. Lipofuscin was measured in the nerve cords (antennal neuropils and oesophageal connectives) in an area adjacent to the brain.Dietary antioxidants significantly affected lipofuscin levels. High vitamin content in the diet resulted in lower percentage of the observed area covered with lipofuscin, lower lipofuscin granule density and lower average granule size. Gender had no effect on any of these variables and granule size did not significantly change within each treatment. Lipofuscin area and granule density increased with age in both vitamin treatments.These results suggest that age estimation using lipofuscin indices may be biased when: (1) wild populations are dispersed over diverse environments; (2) the age estimation of wild individuals is based on the results obtained using laboratory-reared individuals.     

Effect of hyperalphalipoproteinemia on structural characteristics of plasma lipoproteins according to electron paramagnetic resonance spin probe findings

Spin probe, a stearic acid derivative, was used to study the structural features of different lipoproteins (LP) from plasma of subjects with different plasma level of high density LP (HDLP). Access of spin probe located in the internal nonpolar regions of HDLP for the reducer, ascorbic acid, was higher in hyperalphalipoproteinemia than in mean values of HDLP cholesterol concentration. An analogous effect was seen in subjects with LP of very low density. Possible causes of such differences as well as their role in biochemical reactions that proceed with LP participation are discussed.     

Microscopic anatomy of small-intestinal lymphoid patches in children and adults

Longitudinal histological sections of lymphoid patches (LP) in the small intestine, stained after van Gieson and with hematoxylin--eosin, obtained from 105 corpses of persons at the age of 0 up to 90 years have been studied. The LP parenchyma is presented as accumulation of lymphoid nodules++ with a germinative center, or without it and diffuse lymphoid tissue. The lymphoid nodules++ situate both in the mucous membrane and in the submucous tela of the small intestine. The area of the LP components in the newborns is the greatest--84% from the whole area of the LP section. During the human life it decreases and by the old age it makes 47%. The lymphoid nodules++ area with the germinative center in the newborns makes 21% from the area of the LP section, in children from 1 to 3 years of age it increases up to 50%, then it gradually decreases and in the elderly age it makes only 3.8%. The diffuse lymphoid tissue in the LP composition is revealed in all age periods. Size of the lymphoid nodules++ patches, situating in the jejunum and ileum walls in the newborns is the same. In children at the age of 10 days--12 years the LP nodules++ in the ileum are larger than those in the sejunum. The size of the LP noduli increase up to the period of the second childhood then decreases. The height of the lymphoid noduli in persons of mature, elderly and old ages decreases twice in comparison with the children of 3-12 years of age.     

Evidence of still-ongoing convergence evolution of the lactase persistence T-13910 alleles in humans

A single-nucleotide variant, C/T(-13910), located 14 kb upstream of the lactase gene (LCT), has been shown to be completely correlated with lactase persistence (LP) in northern Europeans. Here, we analyzed the background of the alleles carrying the critical variant in 1,611 DNA samples from 37 populations. Our data show that the T(-13910) variant is found on two different, highly divergent haplotype backgrounds in the global populations. The first is the most common LP haplotype (LP H98) present in all populations analyzed, whereas the others (LP H8-H12), which originate from the same ancestral allelic haplotype, are found in geographically restricted populations living west of the Urals and north of the Caucasus. The global distribution pattern of LP T(-13910) H98 supports the Caucasian origin of this allele. Age estimates based on different mathematical models show that the common LP T(-13910) H98 allele (approximately 5,000-12,000 years old) is relatively older than the other geographically restricted LP alleles (approximately 1,400-3,000 years old). Our data about global allelic haplotypes of the lactose-tolerance variant imply that the T(-13910) allele has been independently introduced more than once and that there is a still-ongoing process of convergent evolution of the LP alleles in humans.     

Age-related decline of sodium-dependent ascorbic acid transport in isolated rat hepatocytes

This study investigated whether the age-related decline in hepatic ascorbic acid (AA) levels in rats was due to altered AA uptake. AA concentrations were 68% lower in freshly isolated hepatocytes from old (24-26 months) versus young (3-5 months; p<0.0005) Fischer 344 rats. When incubated with 100 microM AA, cells from old as compared to young rats showed a 66% decline in both the rate of AA transport and the steady state intracellular levels. Sodium-free media significantly reduced AA uptake, suggesting that the sodium-dependent vitamin C transporter (SVCT) was largely responsible for declines in AA transport. Analysis of SVCT messenger RNA (mRNA) levels shows that one isoform of this transport protein, SVCT1, declines 45% with age, with no significant changes in SVCT2 mRNA levels.These results show for the first time that sodium-dependent AA transport declines during the aging process, which may account for much of the loss in tissue AA content.     

Changes in ascorbic acid levels in apoplastic fluid during growth of pine hypocotyls. Effect on peroxidase activities associated with cell walls

The apoplastic fluid of pine ( Pinus pinaster Aiton) hypocotyls contains ascorbic acid (AA) and dehydroascorbic acid (DHA). The amounts of ascorbic and dehydroascorbic acids were in the nmol (g fresh weight)⁻¹ range and decreased with the hypocotyl age as well as along the hypocotyl axis. The ratio AA/(AA+DHA) also decreased with the hypocotyl age and along the hypocotyl. Both ascorbic oxidase and peroxidase activity against ascorbic acid showed very low activity not only in the apoplastic fluid but also in the fractions ionically and covalently bound to the cell walls. However, the peroxidase activity in the three abovementioned fractions was strongly increased in the presence of ferulic acid. That stimulation effect increased with the hypocotyl age and from the apical towards the basal region of the hypocotyls of 10-day-old seedlings. Furthermore, the oxidation of ferulic acid by apoplastic and ionically- and covalently-bound peroxidases was inhibited by ascorbic acid as long as ascorbate was available. A regulatory role of apoplastic ascorbic acid levels in the formation of dehydrodiferulic bridges between wall polysaccharides catalysed by cell wall peroxidases and thus in the cell wall stiffening during plant growth is proposed.     

Comparison between nonlinear and linear periodized resistance training: hypertrophic and strength effects

The aim of this study was to investigate the effects of nonlinear periodized (NLP) and linear periodized (LP) resistance training (RT) on muscle thickness (MT) and strength, measured by an ultrasound technique and 1 repetition maximum (1RM), respectively. Thirty untrained men were randomly assigned to 3 groups: NLP (n = 11, age: 30.2 ± 1.1 years, height: 173.6 ± 7.2 cm, weight: 79.5 ± 13.1 kg), LP (n = 10, age: 29.8 ± 1.9 years, height: 172.0 ± 6.8 cm, weight: 79.9 ± 10.6 kg), and control group (CG; n = 9, age: 25.9 ± 3.6 years, height: 171.2 ± 6.3 cm, weight: 73.9 ± 9.9 kg). The right biceps and triceps MT and 1RM strength for the exercises bench press (BP), lat-pull down, triceps extension, and biceps curl (BC) were assessed before and after 12 weeks of training. The NLP program varied training biweekly during weeks 1-6 and on a daily basis during weeks 7-12. The LP program followed a pattern of intensity and volume changes every 4 weeks. The CG did not engage in any RT. Posttraining, both trained groups presented significant 1RM strength gains in all exercises (with the exception of the BP in LP). The 1RM of the NLP group was significantly higher than LP for BP and BC posttraining. There were no significant differences in biceps and triceps MT between baseline and posttraining for any group; however, posttraining, there were significant differences in biceps and triceps MT between NLP and the CG. The effect sizes were higher in NLP for the majority of observed variables. In conclusion, both LP and NLP are effective, but NLP may lead to greater gains in 1RM and MT over a 12-week training period.     

Flow cytometric purification of Alzheimer's disease amyloid plaque core protein using thioflavin T

Amyloid plaque core protein (APCP) of Alzheimer's disease obtained from brain tissue homogenate is difficult to recover in pure form, primarily because of contaminating lipofuscin (LF) granules. Thioflavin T, a fluorescent dye previously used to stain amyloid, was found to bind to APCP but not to lipofuscin. The latter, however, is autofluorescent. Fluorometric studies showed that at 370 nm excitation APCP has a maximal emission at 418 nm, whereas the autofluorescent LP has a maximal emission at 450 nm. This difference in emission permitted the use of a flow cytometer-sorter (FACS 440) for purification of APCP. APCP particles fluoresced distinctly from LF granules on the log blue fluorescence parameter. The two entities were sorted using forward light scatter versus fluorescence. A collection apparatus was designed and prepared to facilitate the collection of large volumes of sheath fluid and particles and to minimize fragmentation of particles during the collection process. The sorted APCP fraction was 98% pure. This work demonstrates how old dyes can be used to perform new tricks and provide a useful method for separating complex protein.     

Age-Related Regional Changes in Hydroxyl Radical Stress and Antioxidants in Gerbil Brain

Abstract— The levels of hydroxyl radicals and oxidized GSH have been examined as indices of oxidative stress in young (3 months), middle-aged (15 months), and old (20–24 months) gerbil brain hippocampus, cortex, and striaturn. The hydroxyl radical stress was estimated by measuring the salicylate hydroxyl radical trapping products 2,5-and 2,3-dihydroxybenzoic acid. The stress was significantly higher in all three brain regions in middle-aged and old gerbils versus young animals (66.0%). Regional comparisons showed that the stress was significantly higher in cortex than in either the hippocampus or striatum of the middle-aged and old gerbils (32.0%). The ratio of oxidized to total GSH also increased progressively in middle-aged and old animals in all three brain regions (p < 0.05, 41.1%), further indicating a general age-related increase in oxidative stress. Parallel to this age-related increase in oxidative stress, a significant, albeit slight (8%), decrease in neuronal number in hippocampal CA1 region was observed in both the middle-aged and old animals. Possible differences in antioxidant levels were also examined. Total GSH levels were similar across age groups (variance <12%). However, the regional comparison showed that it was highest in striatum in all age groups. The levels of a-tocopherol (vitamin E) were significantly higher in the middle-aged and old animals in all three regions (70.4%). Vitamin E was highest in the hippocampus and the differences between the hippocampus and the cortex and striatum increased with age. Although of a lesser magnitude, significant increases in hippocampal total ascorbic acid level were also noted with age (p < 0.05, 10%). Ascorbic acid was the most regionally specific of the three antioxidants examined, with hippocampus > cortex > striatum for all age groups. The difference in ascorbic acid level between hippocampus and cortex also increased with age (64.4%). The results suggest that the general age-related, regionally specific increases in oxidative stress stimulate the accumulation of antioxidants. It is interesting that the hippocampus, which is selectively vulnerable to various insults such as ischemia, epilepsy, and insulin-induced hypoglycemia, exhibits the greatest age-related increase in vitamin E and ascorbic acid, perhaps reflective of a greater impact of the progressive increase in baseline oxidative stress.     

Effect of gamma irradiation on liver metallothionein synthesis and lipid peroxidation in rats.

Several studies have recently shown that metallothionein (MT), a protein characterized by a high thiol content and that binds Zn2+ and Cu+, might be involved in the protection against oxidative stress and can act as a free radical scavenger. Oxidative stresses, such as irradiation, increase lipid peroxidation (LP) and subsequent tissue damage through free radical production. The induction of hepatic MT synthesis by gamma-irradiation (20 Gy) at 8, 24, 30 and 48 hrs. post-irradiation in two different age groups of Sprague-Dawley rats (39-40 and 48-49 days old) was studied. LP measured by the thiobarbituric acid reactive substances (TBARS) assay and Cu and Zn levels in liver have also been determined. In the younger group, the gamma-irradiation induced hepatic MT synthesis and increased LP that peaked 24 hrs. after irradiation. During the first 30 hrs. post-irradiation, a positive and statistically significant correlation between hepatic MT content and LP level in liver was found. In the older group, liver MT synthesis was only increased 1.7-fold and LP levels were not altered at 24 hrs. post-irradiation compared with sham-irradiated rats.Therefore it appears that LP is not necessary for induction of MT synthesis by gamma-irradiation.