Christina Tsitsimpikou

Histopathological lesions, oxidative stress and genotoxic effects in liver and kidneys following long term exposure of rabbits to diazinon and propoxur.

PURPOSE The aim of the present study was to investigate the effects of diazinon and propoxur on liver and kidneys, following long term exposure of rabbits. METHODS Ten New Zealand white female rabbits were used. The animals were divided into 5 groups, consisting of 2 animals each. Diazinon (groups 1 and 2) and propoxur (groups 3 and 4) were administered at 2 different doses, and group 5 served as the control group. Histopathological lesions in the liver and kidneys, oxidative stress and oxidative DNA damage were evaluated. RESULTS Both pesticides induced focal inflammation and fibrosis in the liver and kidneys. The low dose of propoxur induced a significant increase in total antioxidant capacity (TAC), with no difference in reduced glutathione (GSH), while the high dose of propoxur induced an increase in GSH with no change in TAC. For diazinon-exposed animals, the opposite findings were observed. Both diazinon and propoxur induced a statistically significant oxidative DNA damage in the liver and kidneys and a subsequent increase in telomerase activity in these tissues, possibly as a counteracting mechanism. Furthermore, systemic inflammation, as depicted by the dose-dependent increase in telomerase activity in peripheral blood mononuclear cells (PBMCs), was observed in propoxur treated animals. CONCLUSIONS Histopathological lesions, oxidative stress and genotoxic effects were induced in liver and kidneys following long term exposure of rabbits to diazinon and propoxur.

Alzheimer’s disease treated patients showed different patterns for oxidative stress and inflammation markers

Alzheimers disease (AD) is the most common type of dementia accounting for 60-80% of the reported cases. The aim of this study was to evaluate levels of certain parameters of oxidative stress and markers of endothelial dysfunction in the blood of 21 AD patients under standard treatment compared with 10 controls, in an attempt to elucidate the contribution of AD to the total oxidative stress status of the patients. Results indicate that IL-6, TNF-α, ADMA and homocysteine levels were significantly elevated in AD patients. Protein carbonyls levels were higher in AD group, while glutathione reductase and total antioxidant capacity were lower, depicting decreased defense ability against reactive oxygen species. Besides, a higher level of advanced glycation end-products was observed in AD patients. Depending on the treatment received, a distinct inflammatory and oxidative stress profile was observed: in Rivastigmine-treated group, IL6 levels were 47% lower than the average value of the remaining AD patients; homocysteine and glutathione reductase were statistically unchanged in the Rivastigmine and Donepezil-Memantine, respectively Donepezil group. Although the study is based on a limited population, the results could constitute the basis for further studies regarding the effect of medication and diet on AD patients.

Simulating real-life exposures to uncover possible risks to human health: A proposed consensus for a novel methodological approach

In real life, consumers are exposed to complex mixtures of chemicals via food, water and commercial products consumption. Since risk assessment usually focuses on individual compounds, the current regulatory approach doesn’t assess the overall risk of chemicals present in a mixture. This study will evaluate the cumulative toxicity of mixtures of different classes of pesticides and mixtures of different classes of pesticides together with food additives (FAs) and common consumer product chemicals using realistic doses after long-term exposure. Groups of Sprague Dawley (CD-SD) rats (20 males and 20 females) will be treated with mixtures of pesticides or mixtures of pesticides together with FAs and common consumer product chemicals in 0.0, 0.25 × acceptable daily intake (ADI)/tolerable daily intake (TDI), ADI/TDI and 5 × ADI/TDI doses for 104 weeks. All animals will be examined every day for signs of morbidity and mortality. Clinical chemistry hematological parameters, serum hormone levels, biomarkers of oxidative stress, cardiotoxicity, genotoxicity, urinalysis and echocardiographic tests will be assessed periodically at 6 month intervals. At 3-month intervals, ophthalmological examination, test for sensory reactivity to different types of stimuli, together with assessment of learning abilities and memory performance of the adult and ageing animals will be conducted. After 24 months, animals will be necropsied, and internal organs will be histopathologically examined. If the hypothesis of an increased risk or a new hazard not currently identified from cumulative exposure to multiple chemicals was observed, this will provide further information to public authorities and research communities supporting the need of replacing current single-compound risk assessment by a more robust cumulative risk assessment paradigm.

Cardiotoxicity in rabbits after a low-level exposure to diazinon, propoxur, and chlorpyrifos:

Lethal cardiac complications leading to death and various arrhythmias have been reported after organophosphate and/or carbamate poisonings. The present study focuses on the long-term effects of repeated low-level exposure to diazinon, propoxur, and chlorpyrifos (CPF) on cardiac function in rabbits. The yearly based experimental scheme of exposure consisted of two oral administration periods, lasting 3 months and 1 month each, interrupted by an 8-month washout period (total duration 12 months). At the end of the experimental scheme, the rabbits underwent an echocardiographic evaluation under sedation, after which they were killed and the tissue and serum samples were collected. A mild localized cardiotoxic effect was established by echocardiography for the three pesticides tested. Severe histological alterations were identified, especially in the diazinon-treated animals in agreement with increased persistence of this pesticide established in the cardiac tissue. In addition, all pesticides tested increased the oxidative stress and oxidative modifications in the genomic DNA content of the cardiac tissues, each one following a distinct mechanism.

New challenges in risk assessment of chemicals when simulating real exposure scenarios; simultaneous multi-chemicals' low dose exposure

The general population experiences uncontrolled multi-chemicals exposure from many different sources at doses around or well below regulatory limits. Therefore, traditional chronic toxicity evaluations for a single chemical could possibly miss to identify adequately all the risks. For this an experimental methodology that has the ambition to provide at one strike multi-answers to multi-questions is hereby proposed: a long-term toxicity study of non-commercial chemical mixtures, consisting of common everyday life chemicals (pesticides, food additives, life-style products components) at low and realistic dose levels around the regulatory limits and with the simultaneous investigation of several key endpoints, like genotoxicity, endocrine disruption, target organ toxicity including the heart and systemic mechanistic pathways, like oxidative stress.

Medication Use by Athletes during the Athens 2004 Paralympic Games

Objective: To examine the use of food supplements and pharmaceutical preparations by elite Paralympic athletes. Design: Survey study. Setting: Athens 2004 Paralympic Games. Participants: Data obtained from two sources: (i) athletes’ declaration of intake of drugs/supplements recorded on the Doping Control Official Record during sample collection for doping control; (ii) athletes’ application forms for granting of a therapeutic use exemption. Main outcome measures: Classification of declared food supplements according to the active ingredient and medications according to therapeutic actions and active compounds. Results: 64.2% of the athletes tested for doping control declared use of medications or food supplements, and 81.3% of these athletes declared intake of fewer than four preparations. Non-invasive routes of administration dominated. Food supplements (42.1%) were popular, and drugs used to treat several pathological conditions noted. Non-steroidal anti-inflammatory agents and analgesics were commonly used (9.8% and 5.6%, respectively). The prevalence of inhaled β2-agonist use (4.8%) was higher than expected and exceeded that at the Athens Olympic Games. Conclusions: This review, the first to examine elite Paralympic athletes, shows a more rational approach to the use of medication and food supplements, but a similar consumption pattern to that of athletes at the Athens Olympic Games. Because of the dearth of such studies, consumption trends among Paralympic athletes remain unclear. The need to counsel athletes with disabilities on their nutritional needs is confirmed, and close monitoring by healthcare professionals is recommended.

Effect of a special carbohydrate-protein cake on oxidative stress markers after exhaustive cycling in humans.

Exercise has been associated with oxidative stress that is correlated with muscle fatigue and reduced exercise performance. The aim of this study was to examine the effects of a special cake (consisting of carbohydrate to whey protein 3.5:1) vs an isocaloric carbohydrate cake on biomarkers of oxidative stress in 9 males after exhaustive cycling. A randomized single-blind cross-over study was completed. They performed one trial involving a 2-h exercise on a cycle ergometer at 60-65% VO(2)max followed by a 4-h recovery and then a second trial involved an 1-h exercise at 60-65% VO(2)max which was increased at 95% VO(2)max (time trial). The subjects received 4 experimental or placebo cakes after the first trial (the first immediately after and then one every hour). Blood samples were collected at eight time intervals: pre-exercise, 30 min, 1.5 h and 4 h post-exercise, post time Trial, 1 h, 24 h and 48 h post time Trial. Thiobarbituric Acid Reactive Substances (TBARS), protein carbonyls, total antioxidant capacity (TAC), catalase and glutathione (GSH) were determined spectrophotometrically. The mean time to exhaustion did not differ upon cake consumption. Consumption of the special cake reduced TBARS significantly, but had no effect on other oxidative stress markers.

Effects of walking on heart rate recovery, endothelium modulators and quality of life in patients with heart failure

Background: Few studies have addressed the impact of moderate unsupervised everyday physical activity in patients with chronic heart failure (CHF). Design: We investigated the effects of a 12-week walking programme as the sole exercise intervention on heart rate recovery (HRR), index of the autonomic system equilibrium, serum modulators of endothelial function (i.e. asymmetric dimethylarginine (ADMA) and homocysteine), markers of inflammation and oxidative stress and quality of life measures (i.e. SF-36 and the Zung depression scale) in CHF patients. Methods: Twenty-eight stabilized CHF patients of ΝYHΑ class II and III volunteered to participate either in the exercise (n = 18) or in the non-exercise (n = 10) groups. Ten age-matched healthy volunteers provided reference values. The exercise programme consisted of unsupervised 40-minute walking for five days per week. Results: Repeated measures ANOVA revealed significant improvements in HRR (p < 0.001) in the exercise patients compared to their non-exercise counterparts. ADMA levels in CHF patients at baseline were found higher than the healthy reference volunteers (p < 0.03), while a decrease in ADMA levels after walking was associated with HRR changes (r = 0.74, p = 0.007). Homocysteine levels both at baseline and at the end of the walking intervention decreased in the exercise group, but were still higher than in the healthy individuals. Average walking distance positively correlated with homocysteine decrease (p < 0.05). Total SF-36 score significantly improved (p < 0.02) mainly due to enhancements in the physical component score (p < 0.026). Conclusion: A 12-week unsupervised walking programme exhibits a pronounced HRR amelioration, possibly attenuates endothelial damage and induces a concomitant improvement in perceived quality of life in CHF patients.

Contrast-induced nephropathy: Basic concepts, pathophysiological implications and prevention strategies☆

&NA; Contrast‐induced nephropathy (CIN) is reversible acute renal failure observed following administration of iodinated contrast media (CM) during angiographic or other medical procedures such as urography. There are various mechanisms through which CM develop their nephrotoxic effects, including oxidative stress and apoptosis. CIN is a real‐life, albeit not very rare, entity. Exact pathophysiology remains obscure and no standard diagnostic criteria apply. The Acute Kidney Injury Network criteria was recently employed but its incidence/clinical significance warrants further clarification based on recent methodological advancements, because most published studies to date were contaminated by bias. The current study is a comprehensive review conducted to provide an overview of the basic concepts of CIN and summarize recent knowledge on its pathophysiology and the evidence supporting potential prevention strategies. CIN is expected to increase morbidity, hospital stay and mortality, while all patients scheduled to receive CM should undergo risk assessment for CIN and high‐risk patients may be considered candidates for prevention strategies. The value of using compounds with antioxidant properties other than sodium bicarbonate, remains controversial, warranting further clinical investigation.

Low-dose occupational exposure to benzene and signal transduction pathways involved in the regulation of cellular response to oxidative stress.

AIMS Benzene metabolism seems to modulate NF-κB, p38-MAPK (mitogen-activated protein kinase) and signal transducer and activator of transcription 3 (STAT3) signalling pathways via the production of reactive oxygen species. This study aims to evaluate the effects of low-dose, long-term exposure on NF-κB, STAT3, p38-MAPK and stress-activated protein kinase/Jun amino-terminal kinase (SAPK/JNK) signal transduction pathways in peripheral blood mononuclear cells in gasoline station attendants. The influence of consumption of vegetables and fruits on these pathways has also been evaluated. MAIN METHODS A total of 91 men, employed in gasoline stations located in eastern Sicily, were enrolled for this study and compared with a control group of 63 male office workers with no history of exposure to benzene. The exposure was assessed by measuring urinary trans,trans-muconic acid (t,t-MA) concentration. Quantitative analyses were performed for proteins NF-κB p65, phospho-NF-κB p65, phospho-IκB-α, phospho-SAPK/JNK, phospho-p38 MAPK and phospho-STAT3 using an immunoenzymatic assay. KEY FINDINGS The results of this study indicate significantly higher t,t-MA levels in gasoline station attendants. With regard to NF-κB, phospho-IκB-α and phospho-STAT3 proteins, statistically significant differences were observed in workers exposed to benzene. However, no differences were observed in SAPK/JNK and p38-MAPK activation. These changes were positively correlated with t,t-MA levels, but only phospho-NF-κB p65 was associated with the intake of food rich in antioxidant active principles. SIGNIFICANCE Chronic exposure to low-dose benzene can modulate signal transduction pathways activated by oxidative stress and involved in cell proliferation and apoptosis. This could represent a possible mechanism of carcinogenic action of chronic benzene exposure.