Metal imbalance and compromised antioxidant function are early changes in prion disease.
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ABSTRACT:
SUBMITTER: Thackray AM
PROVIDER: S-EPMC1222383 | biostudies-other | 2002 Feb
REPOSITORIES: biostudies-other
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Project description:Noise has been regarded as an environmental/occupational stressor that causes damages to both auditory and non-auditory organs. Prolonged exposure to these mediators of stress has often resulted in detrimental effect, where oxidative/nitrosative stress plays a major role. Hence, it would be appropriate to examine the possible role of free radicals in brain discrete regions and the "antioxidants" mediated response of S. dulcis. Animals were subjected to noise stress for 15 days (100 dB/4 hours/day) and estimation of endogenous free radical and antioxidant activity were carried out on brain discrete regions (the cerebral cortex, cerebellum, brainstem, striatum, hippocampus and hypothalamus). The result showed that exposure to noise could alleviate endogenous free radical generation and altered antioxidant status in brain discrete regions when compared to that of the control groups. This alleviated free radical generation (H2O2 and NO) is well supported by an upregulated protein expression on immunohistochemistry of both iNOS and nNOS in the cerebral cortex on exposure to noise stress. These findings suggest that increased free radical generation and altered anti-oxidative status can cause redox imbalance in the brain discrete regions. However, free radical scavenging activity of the plant was evident as the noise exposed group treated with S. dulcis[200 mg/(kg·b·w)] displayed a therapeutic effect by decreasing the free radical level and regulate the anti-oxidative status to that of control animals. Hence, it can be concluded that the efficacy of S. dulcis could be attributed to its free radical scavenging activity and anti-oxidative property.
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Project description:This study examined the impact of early weaning on antioxidant function in piglets. A total of 40 Duroc × Landrace × Large White, 21-day-old piglets (half male and half female) were divided into suckling groups (SG) and weaning groups (WG). Piglets in WG were weaned at the 21st day, while the piglets in SG continued to get breastfed. Eight piglets from each group were randomly selected and slaughtered at 24th-day (SG3, WG3) and 28th-day old (SG7, WG7). The body weight, liver index, hepatocyte morphology, antioxidant enzymes activity, gene expression of antioxidant enzymes, and Nrf2 signaling in the liver of piglets were measured. The results showed that weaning caused decreased body weight (p < 0.01), lower liver weight (p < 0.01), and decreased the liver organ index (p < 0.05) of piglets. The area and size of hepatocytes in the WG group was smaller than that in the SG group (p < 0.05). We also observed that weaning reduced the activity of superoxide dismutase (SOD) and catalase (CAT) (p < 0.05) in the liver of piglets. Relative to the SG3 group, the gene expression of GSH-Px in liver of WG3 was significantly reduced (p < 0.05). The gene expression of Nrf2 in the SG3 group was higher than that in the WG3 group (p < 0.01). The gene expression of NQO1 in the SG7 group was higher than that in the WG7 group (p < 0.05). In conclusion, weaning resulted in lower weight, slowed liver development, and reduced antioxidant enzymes activity, thereby impairing liver antioxidant function and suppressing piglet growth.
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Project description:BackgroundWe investigated the pathological and diagnostic role of selected markers of inflammation, oxidant/antioxidant status, and cellular injury in human Chagas disease.MethodsSeropositive/chagasic subjects characterized as clinically-symptomatic or clinically-asymptomatic (n = 116), seronegative/cardiac subjects (n = 102), and seronegative/healthy subjects (n = 45) were analyzed for peripheral blood biomarkers.ResultsSeropositive/chagasic subjects exhibited an increase in sera or plasma levels of myeloperoxidase (MPO, 2.8-fold), advanced oxidation protein products (AOPP, 56%), nitrite (5.7-fold), lipid peroxides (LPO, 12-17-fold) and malondialdehyde (MDA, 4-6-fold); and a decline in superoxide dismutase (SOD, 52%) and glutathione (GSH, 75%) contents. Correlation analysis identified a significant (p<0.001) linear relationship between inflammatory markers (AOPP/nitrite: r = 0.877), inflammation and antioxidant/oxidant status (AOPP/glutathione peroxidase (GPX): r = 0.902, AOPP/GSH: r = 0.806, Nitrite/GPX: 0.773, Nitrite/LPO: 0.805, MDA/MPO: 0.718), and antioxidant/oxidant levels (GPX/MDA: r = 0.768) in chagasic subjects. Of these, MPO, LPO and nitrite biomarkers were highly specific and sensitive for distinguishing seropositive/chagasic subjects from seronegative/healthy controls (p<0.001, training and fitting AUC/ROC >0.95). The MPO (r = 0.664) and LPO (r = 0.841) levels were also correlated with clinical disease state in chagasic subjects (p<0.001). Seronegative/cardiac subjects exhibited up to 77% decline in SOD, 3-5-fold increase in LPO and glutamate pyruvate transaminase (GPT) levels, and statistically insignificant change in MPO, AOPP, MDA, GPX, GSH, and creatine kinase (CK) levels.ConclusionsThe interlinked effects of innate immune responses and antioxidant/oxidant imbalance are major determinants of human Chagas disease. The MPO, LPO and nitrite are excellent biomarkers for diagnosing seropositive/chagasic subjects, and MPO and LPO levels have potential utility in identifying clinical severity of Chagas disease.
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Project description:Converging evidence leaves little doubt that a change in the conformation of prion protein (PrP(C)) from a mainly alpha-helical to a beta-sheet rich PrP-scrapie (PrP(Sc)) form is the main event responsible for prion disease associated neurotoxicity. However, neither the mechanism of toxicity by PrP(Sc), nor the normal function of PrP(C) is entirely clear. Recent reports suggest that imbalance of iron homeostasis is a common feature of prion infected cells and mouse models, implicating redox-iron in prion disease pathogenesis. In this report, we provide evidence that PrP(C) mediates cellular iron uptake and transport, and mutant PrP forms alter cellular iron levels differentially. Using human neuroblastoma cells as models, we demonstrate that over-expression of PrP(C) increases intra-cellular iron relative to non-transfected controls as indicated by an increase in total cellular iron, the cellular labile iron pool (LIP), and iron content of ferritin. As a result, the levels of iron uptake proteins transferrin (Tf) and transferrin receptor (TfR) are decreased, and expression of iron storage protein ferritin is increased. The positive effect of PrP(C) on ferritin iron content is enhanced by stimulating PrP(C) endocytosis, and reversed by cross-linking PrP(C) on the plasma membrane. Expression of mutant PrP forms lacking the octapeptide-repeats, the membrane anchor, or carrying the pathogenic mutation PrP(102L) decreases ferritin iron content significantly relative to PrP(C) expressing cells, but the effect on cellular LIP and levels of Tf, TfR, and ferritin is complex, varying with the mutation. Neither PrP(C) nor the mutant PrP forms influence the rate or amount of iron released into the medium, suggesting a functional role for PrP(C) in cellular iron uptake and transport to ferritin, and dysfunction of PrP(C) as a significant contributing factor of brain iron imbalance in prion disorders.
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Project description:Altered thyroid function during early stages of development is known to affect adversely testicular growth, physiology, and antioxidant defence status at adulthood. The objective of the present study is to investigate the modulation of antioxidant defence status in neonatal persistent hypothyroid rats before their sexual maturation and also to identify the specific testicular cell populations vulnerable to degeneration during neonatal hypothyroidism in immature rats. Hypothyroidism was induced in neonates by feeding the lactating mother with 0.05% 6-n-propyl-2-thiouracil (PTU) through the drinking water. From the day of parturition till weaning (25 day postpartum), the pups received PTU through mother's milk (or) drinking water and then directly from drinking water containing PTU for the remaining period of experimentation. On the 31st day postpartum, the animals were sacrificed for the study. An altered antioxidant defence system marked by elevated SOD, CAT, and GR activities, with decreased GPx and GST activities were observed along with increased protein carbonylation, disturbed redox status in hypothyroid immature rat testis. This compromised testicular antioxidant status might have contributed to poor growth and development by affecting the spermatogenesis and steroidogenesis in rats before puberty as indicated by reduced germ cell number, complete absence of round spermatids, decreased seminiferous tubule diameter, and decreased testosterone level.
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