Imbalance in superoxide dismutase/thioredoxin reductase activities in hypercholesterolemic subjects: relationship with low density lipoprotein oxidation.

BACKGROUND: There is a relationship among hypercholesterolemia, oxidative stress and inflammation in the atherogenesis. Thus, the objective of the present study was to assess paraoxonase (PON1), superoxide dismutase (SOD) and thioredoxin reductase (TrxR-1) activities and their relationship with lipids, oxidative stress and inflammation in subjects with different low density lipoprotein-cholesterol (LDL) levels. METHODS: Serum lipids, highly sensitive C-reactive protein (hs-CRP), lipid and protein oxidation, oxidized LDL (LDLox) and LDLox autoantibodies (LDLoxAB) levels and enzymes activities were measured in a total of 116 subjects that were divided into the following groups according to their LDL levels: low-LDL group (LDL < 100 mg/dL, n = 23), intermediate-LDL group (LDL 100-160 mg/dL, n = 50) and high-LDL group (LDL > 160 mg/dL, n = 43). RESULTS: The LDLox and hs-CRP levels increased in the high-LDL group (2.7- and 3.7- fold, respectively), whereas the intermediate and high-LDL groups had higher LDLoxAB (2.2- and 3.1-fold) when compared to low-LDL group (p < 0.05). Similarly, SOD activity, the atherogenic index (AI) and protein oxidation were also higher in the intermediate (1.3-, 1.3- and 1.2-fold) and high-LDL (1.6-, 2.3- and 1.6-fold) groups when compared to the low-LDL group (p < 0.05). Lipid oxidation and SOD/TrxR-1 ratio increased only in the high-LDL group (1.3- and 1.6-fold) when compared to the low-LDL group (p < 0.05). The SOD/TrxR-1 ratio was positively correlated to TBARS (r = 0.23, p < 0.05), LDLox (r = 0.18, p < 0.05), LDLoxAB (r = 0.21, p < 0.05), LDL (r = 0.19, p < 0.05) and AI (r = 0.22, p < 0.05). PON1 and TrxR-1 activities were similar among groups. CONCLUSIONS: Some oxidative events initiate when LDL levels are clinically acceptable. Moreover, hypercholesterolemic patients have an imbalance in SOD and TrxR-1 activities that is positively associated to LDL oxidation.

Adenine nucleotide hydrolysis in patients with aseptic and bacterial meningitis.

The meningitis is a disease with high mortality rates capable to cause neurologic sequelae. The adenosine (the final product of ATP hydrolysis by ectonucleotidases), have a recognized neuroprotective actions in the central nervous system (CNS) in pathological conditions. The aim of the present study was evaluate the adenine nucleotides hydrolysis for to verify one possible role of ATP, ADP and AMP hydrolysis in inflammatory process such as meningitis. The hydrolysis was verified in cerebrospinal fluid (CSF) from human patients with aseptic and bacterial meningitis. Our results showed that the ATP hydrolysis was reduced 12.28% (P < 0.05) in bacterial meningitis and 22% (P < 0.05) in aseptic meningitis. ADP and AMP hydrolysis increased 79.13% (P < 0.05) and 26.37% (P < 0.05) in bacterial meningitis, respectively, and 57.39% (P < 0.05) and 42.64% (P < 0.05) in aseptic meningitis, respectively. This may be an important protective mechanism in order to increase adenosine production.

Oxidative stress in cerebrospinal fluid of patients with aseptic and bacterial meningitis.

This study aimed to determine whether patients with aseptic and bacterial meningitis presented alterations in oxidative stress parameters of cerebrospinal fluid (CSF). A total of 30 patients were used in the research. The CSF oxidative stress status has been evaluated through many parameters, such as lipid peroxidation through thiobarbituric acid reactive substances (TBARS) and antioxidant defense systems such as superoxide dismutase (SOD), glutathione S-transferase (GST), reduced glutathione (GSH) and ascorbic acid. TBARS levels, SOD and GST activity increase in aseptic meningitis and in bacterial meningitis. The ascorbic acid concentration increased significantly in patients with both meningitis types. The reduced glutathione levels were reduced in CSF of patients with aseptic and bacterial meningitis. In present study we may conclude that oxidative stress contributes at least in part to the severe neurological dysfunction found in meningitis.

The antidepressant effect of bone marrow mononuclear cell transplantation in chronic stress.

BACKGROUND: Inflammation could be a risk factor for the development of depression and change the outcome of this common chronic-recurrent mental disorder. AIMS: This study aimed to investigate if bone marrow mononuclear cell (BMMC) transplantation is effective in restoring sucrose preference in rats subjected to chronic stress (CS), if it has an anti-inflammatory effect and is able to restore damaged DNA. METHODS: The effect of BMMC transplantation was studied in a controlled protocol (compared with a control group and a selective serotonin reuptake inhibitor escitalopram group) involving sucrose preference in CS in rats. Measurements were taken of the amygdala, hippocampus, frontal cortex, and other brain areas, the spleen and blood pro-inflammatory cytokines, namely interleukin-1ß, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma, as well as anti-inflammatory cytokine interleukin-10. Finally, 8-hydroxy-2'-deoxyguanosine (a DNA damage marker) was determined. RESULTS: BMMC transplantation was as effective as escitalopram in restoring sucrose preference. It also had an anti-inflammatory effect and slightly improved damaged DNA after one week. CONCLUSIONS: These findings suggest administration of BMMC in rats subjected to CS restores sucrose preference, resolves inflammation in both the peripheral and central nervous system, as well as diminishes DNA damage. This effect was similar to that of escitalopram, which is effective in the treatment of depressive patients.

Caffeine and high intensity exercise: Impact on purinergic and cholinergic signalling in lymphocytes and on cytokine levels.

This study evaluated the effects of caffeine in combination with high-intensity interval training (HIIT) on sensitivity to glucocorticoids and proliferation of lymphocytes, IL-6 and IL-10 levels and NTPDase, adenosine deaminase (ADA) and acetylcholinesterase (AChE) activity in rat lymphocytes. The animals were divided into groups: control, caffeine 4 mg/kg, caffeine 8 mg/kg, HIIT, HIIT plus caffeine 4 mg/kg and HIIT plus caffeine 8 mg/kg. The rats were trained three times a week for 6 weeks for a total workload 23% of body weight at the end of the experiment. Caffeine was administered orally 30 min before the training session. When lymphocytes were stimulated with phytohaemagglutinin no changes were observed in proliferative response between trained and sedentary animals; however, when caffeine was associated with HIIT an increase in T lymphocyte proliferation and in the sensitivity of lymphocytes to glucocorticoids occurred. ATP and ADP hydrolysis was decreased in the lymphocytes of the animals only trained and caffeine treatment prevented alterations in ATP hydrolysis. HIIT caused an increase in the ADA and AChE activity in lymphocytes and this effect was more pronounced in rats trained and supplemented with caffeine. The level of IL-6 was increased while the level of IL-10 was decreased in trained animals (HIIT) and caffeine was capable of preventing this exercise effect. Our findings suggest that caffeine ingestion attenuates, as least in part, the immune and inflammatory alterations following a prolonged HIIT protocol.

Enzymes that hydrolyze adenine nucleotides of patients with hypercholesterolemia and inflammatory processes.

The activity of NTPDase (EC 3.6.1.5, apyrase, CD39) was verified in platelets from patients with increasing cholesterol levels. A possible association between cholesterol levels and inflammatory markers, such as oxidized low-density lipoprotein, highly sensitive C-reactive protein and oxidized low-density lipoprotein autoantibodies, was also investigated. Lipid peroxidation was estimated by measurement of thiobarbituric acid reactive substances in serum. The following groups were studied: group I, < 150 mg.dL(-1) cholesterol; group II, 151-200 mg.dL(-1) cholesterol; group III, 201-250 mg.dL(-1) cholesterol; and group IV, > 251 mg.dL(-1) cholesterol. The results demonstrated that both ATP hydrolysis and ADP hydrolysis were enhanced as a function of cholesterol level. Low-density lipoprotein levels increased concomitantly with total cholesterol levels. Triglyceride levels were increased in the groups with total cholesterol above 251 mg.dL(-1). Oxidized low-density lipoprotein levels were elevated in groups II, III, and IV. Highly sensitive C-reactive protein was elevated in the group with cholesterol levels higher than 251 mg.dL(-1). Oxidized low-density lipoprotein autoantibodies were elevated in groups III and IV. Thiobarbituric acid reactive substance content was enhanced as a function of cholesterol level. In summary, hypercholesterolemia is associated with enhancement of inflammatory response, oxidative stress, and ATP and ADP hydrolysis. The increased ATP and ADP hydrolysis in group IV was confirmed by an increase in CD39 expression on its surface. The increase in CD39 activity is possibly related to a compensatory response to the inflammatory and pro-oxidative state associated with hypercholesterolemia.

Diphenyl diselenide supplementation reduces biochemical alterations associated with oxidative stress in rats fed with fructose and hydrochlorothiazide.

The study evaluated whether a diet containing diphenyl diselenide (PhSe)2, a synthetic antioxidant, could reduce the biochemical alterations induced by chronic consumption of highly enriched fructose diet and/or hydrochlorothiazide (HCTZ). Rats were fed a control diet (CT) or a high fructose diet (HFD), supplemented with or not HCTZ (4.0g/kg) and/or (PhSe)2 (3ppm) for 18weeks. HFD intake increased significantly plasma glucose, fructosamine, triglycerides and cholesterol levels. (PhSe)2 supplementation significantly reduced triglycerides and cholesterol but could not restore them to control levels. The combination of HFD and HCTZ significantly altered plasma glucose, fructosamine, triglycerides and cholesterol levels which were not restore by (PhSe)2 supplementation. Lipid peroxidation, protein carbonyl formation, vitamin C level and catalase activity decreased after HFD, HCTZ or HFD plus HCTZ ingestion. Remarkably (PhSe)2 supplementation restored the oxidative stress parameters. HCTZ decreased renal superoxide dismutase (SOD) activity, which was restored to control levels by (PhSe)2. Furthermore, the association of HFD and HCTZ decreased plasma potassium levels and aggravated HCTZ-induced hypomagnesemia and hypertriglyceridemia. Here we provided evidence of the involvement of oxidative stress and metabolic disorders in a rat model of HFD associated or not with HTCZ. (PhSe)2 supplementation reduced the oxidative stress and this compound should be considered for the treatment of biochemical disturbances and oxidative stress in other animal models of metabolic disorders.