In deep evaluation of the neurotoxicity of orally administered TiO2 nanoparticles.

Titanium dioxide nanoparticles were widely used in food as dietary supplements, in drugs, in toothpaste, ect. Few numbers of studies were interested to the neurotoxicity of TiO2 NPs through oral pathway. The present study aims firstly to understand the connection between the physicochemical properties of TiO2 NPs and their associated toxicological oral pathway by evaluation the colloidal stability of TiO2 NPs over time in different media simulating physiological gastric, intestinal and serum conditions at 37 °C to be close to the oral administraton. Secondly, this study aims to evaluate the neurotoxicity of a subchronic intragastric administration of TiO2 NPs to rats. Different doses of anatase TiO2 NPs were administrated to Wistar rats every day for consecutives eight weeks. Titanium (Ti) content in brain, oxidative antioxidant biomarkers, lipid peroxidation, nitric oxide (NO) levels, tumor necrosis factor-alpha (TNF-α) levels, histophatological changes, degenerated and apoptosis neurons were investigated. Results suggested that TiO2 NPs can reach the brain and cross the brain blood barrier (BBB) to been accumulated in the brain of rats causing cerebral oxidative stress damage, increasing NO levels and histopathological injury. At higher dose, we observed the most cerebral injury by the highest accumulation of Ti and by the remarkable increase of TNF-α besides to the most increase of degenerated and apoptosis neurons in the brain of exposed rats. TiO2 NPs led to a neurotoxic damage accompanied by the increase of degenerated and apoptotic neurons in cerebral cortex.

Evaluation of resistance to temephos insecticide in Culex pipiens pipiens larvae collected from three districts of Tunisia.

BACKGROUND: Mosquitoes are considered as the main groups of arthropods that cause nuisance and public health problems. OBJECTIVES: Evaluation of resistance to temephos insecticide in Culex pipiens pipiens larvae collected from three districts of Tunisia. METHODS: Late third and early fourth instars larvae of Culex pipiens pipiens were collected in three localities of Northern and Southern Tunisia. Field collected populations were tested against temephos insecticide and compared to bioassays of a susceptible reference strain. The cross-resistance between temephos and propoxur, and the polymorphism of over-produced esterases and AChE 1 were investigated. RESULTS: Studied populations exhibited tolerance to temephos with low and high levels of resistance. The resistance ratio (RR50) values of temephos ranged from 1.34 to 114. Synergists and starch electrophoresis showed that the metabolic resistances were involved in the recorded resistance. Likewise, the resistant target site (acetyl cholinesterase: AChE 1) was responsible for the recorded resistance to temephos compound in Culex pipiens pipiens. CONCLUSION: The low and high resistance recorded to temephos insecticides is particularly interesting, because it leaves a range of tools useable by vector control services. However, further studies are needed to determine its spread and anticipate vector control failure where these insecticides are used.

Relationship between sperm DNA damage with sperm parameters, oxidative markers in teratozoospermic men.

OBJECTIVE: This study was aimed at determining the extent of sperm nuclear DNA damage in patients with isolated teratozoospermia and examining its relationship with oxidative stress. STUDY DESIGN: Semen samples from 60 patients with isolated teratozoospermia and 30 normozoospermic donors were examined. DNA damage was evaluated by the COMET assay. Seminal antioxidant activities (Superoxide dismutase; Glutathione peroxidase; Catalase), iron and malondialdehyde concentrations were measured spectrophotometrically. RESULTS: Sperm DNA damage; malondialdehyde and iron levels were more elevated in studied groups than controls. Nevertheless, the antioxidant enzyme activity obtained was significantly lower in the group of patients with teratozoospermia compared to the controls. Sperm DNA damage was positively correlated to malondialdehyde and seminal iron level while reduced seminal antioxidant status was negatively associated with sperm DNA breaks. Interestingly, we noted that sperm DNA damage; lipid peroxidation, iron level, and impaired antioxidant status were negatively correlated to normal sperm morphology. CONCLUSION: These findings may explain the complex biological relationship between teratozoospermia, oxidative stress, and DNA damage. In fact, an impaired seminal antioxidant status and an increased seminal level of both lipid peroxidation and iron can affect sperm nuclear integrity resulting in DNA breaks and can be associated with poor sperm morphology.

Resistance status to deltamethrin pyrethroid of Culex pipiens pipiens (Diptera: Culicidae) collected from three districts of Tunisia.

OBJECTIVES: The aim of the present study was to determine the susceptibility status of Culex pipiens pipiens populations against deltamehtrin insecticide. METHODS: Larvae of Culex pipiens pipiens were collected from three breeding places in Northern and Southern Tunisia between 2003 and 2005. Early third and late fourth instars were tested against deltamethrin pyrethroid insecticide. Cross-resistance with DDT resistance was evaluated in studied samples to estimate the role of target site insensitivity and two synergists including piperonyl butoxide (Pb) and S,S,S-tributyl phosphorotrithioate (DEF) were used to estimate the role of detoxification enzymes. RESULTS: Our results revealed that the level of deltamehtrin resistance ranged from 0.67 to 31.4. We also showed the non-involvement of kdr resistance in pyrethroid resistance and no cross-resistance with DDT resistance was detected in all studied populations including the most resistant one. Synergists study on the resistant population (sample # 1) showed the involvement of CYP450 in the recorded resistance to the deltamethrin insecticide. CONCLUSION: The results obtained from this study should be considered in the current control programs to combat mosquitoes in Tunisia.

Resistance development and insecticide susceptibility in Culex pipiens pipiens, an important vector of human diseases, against selection pressure of temephos and its relationship to cross-resistance towards organophosphates and pyrethroids insecticides.

BACKGROUND: Culex pipiens pipiens is an important vector of human diseases. OBJECTIVE: To determine the insecticide resistance development in Culex pipiens pipiens against selection pressure of temephos.. METHODS: A field population of Culex pipiens pipiens was collected from Northwestern Tunisia with a medium level of temephos resistance (LC50 = 0.0069). It was subjected to six generations of temephos pressure selection to evaluate its relationship to cross-resistance towards organophosphates (OPs) and pyrethroids (PYR) insecticides. RESULTS: The selection was initiated at the dose 0.0266, 0.0748 and 0.0069 which were increased during successive generations up to 0.1488, 3.8747 and 0.0086 after sixth generation for temephos, chlorpyrifos and permethrin insecticides, respectively. It is important to noted that high cross-resistance to chlorpyrifos insecticide (OP) was detected (51.88×). However, little or no cross-resistance to the pyrethroid permethrin (PYR) was recorded (1.24×). Contrary to metabolic resistance, it seemed that acetylcholinesterases AChE 1 was fixed under pressure selection. CONCLUSION: The high cross-resistance to temephos and chlorpyrifos is reasonable because they belong to the same class of insecticide (OP). However, the little cross-resistance to the pyrethroid permethrin could support its use alternately for Culex pipiens pipiens control.

Rosmarinus officinalis L. ameliorates titanium dioxide nanoparticles and induced some toxic effects in rats' blood.

Titanium dioxide nanoparticles (TiO2 NPs) have been widely used as a white pigment in food and drugs. The most important route of human exposure to TiO2 is through food and drug products containing TiO2 additives. This study investigates the efficacy of an oral traditional use of rosemary extract in ameliorating some toxic effects induced on blood of TiO2 NP-intoxicated rats. Rats were given rosemary extract via intragastric administration 1 h before the intragastric administration of 100 mg/kg/day TiO2 NPs (10 nm) for 60 days. TiO2 NPs significantly increased serum cholesterol, glucose, and triglyceride levels of rats. They also induced significant oxidative stress and inflammatory and caused DNA damage in peripheral blood leukocytes. The rosemary extract appears to have a significant protective effect by lowering glucose level properties, restoring the lipid profile and showing an antioxidative, anti-inflammatory, and antigenotoxic properties against TiO2 NPs toxicity. In conclusion, this study gives an encouraging scientific basis for consumers of rosemary leaves to keep on with this culinary habit.

The effect of titanium dioxide nanoparticles on neuroinflammation response in rat brain.

Titanium dioxide nanoparticles (TiO2 NPs) are widely used for their whiteness and opacity in several applications such as food colorants, drug additives, biomedical ceramic, and implanted biomaterials. Research on the neurobiological response to orally administered TiO2 NPs is still limited. In our study, we investigate the effects of anatase TiO2 NPs on the brain of Wistar rats after oral intake. After daily intragastric administration of anatase TiO2 NPs (5-10 nm) at 0, 50, 100, and 200 mg/kg body weight (BW) for 60 days, the coefficient of the brain, acethylcholinesterase (AChE) activities, the level of interleukin 6 (IL-6), and the expression of glial fibrillary acidic protein (GFAP) were assessed to quantify the brain damage. The results showed that high-dose anatase TiO2 NPs could induce a downregulated level of AChE activities and showed an increase in plasmatic IL-6 level as compared to the control group accompanied by a dose-dependent decrease inter-doses, associated to an increase in the cerebral IL-6 level as a response to a local inflammation in brain. Furthermore, we observed elevated levels of immunoreactivity to GFAP in rat cerebral cortex. We concluded that oral intake of anatase TiO2 NPs can induce neuroinflammation and could be neurotoxic and hazardous to health.

Toxicopathic changes and genotoxic effects in liver of rat following exposure to diazinon.

In general, people may come in contact with mixtures of insecticides through domestic use, consumption of contaminated food or drinks, and/or living close to treated areas. We analyzed the toxic effects of diazinon on histological structure of liver and hematological parameters in male rats. DNA-damaging potential of diazinon was also investigated using the comet assay in blood cells and the micronucleus test in bone marrow. Two groups of six male rats orally received different amounts of diazinon: 1/50 and 1/25 LD 50 for 4 weeks (5 day/week). The present study showed that diazinon caused hypertrophy of sinusoids, central vein, and portal triad, in addition to the formation of oedema, vacuoles, hemorrhage, necrosis, and lymphoid infiltration in rats' liver. A significant decrease in red blood cells, hemoglobin, hematocrite levels, and platelet counts was observed in the treated groups. However, the white blood cell count increased. Micronucleus test results revealed aneugenic effects of diazinon. Furthermore, we noticed an increase in comet tail length in treated groups. So, the comet assay confirmed the genotoxic potential of diazinon in vivo. On the assumption that all alterations observed in rats could be observed in human, it is necessary to raise the awareness about the health risk posed by this insecticide.

Thymoquinone ameliorates lead-induced suppression of the antioxidant system in rat kidneys.

Objective Alteration of the antioxidant status in the kidneys may be related to lead (Pb) intoxication. The present study aimed to investigate the possible beneficial effect of thymoquinone (TQ), the major active ingredient of the volatile oil of Nigella sativa seeds, on Pb-induced renal antioxidant defense system impairment. Methods A total of thirty two healthy adult male Wistar rats were randomly divided into four equal groups as follows: a control group, which received no treatment; a Pb group, which was exposed to 2,000 ppm of Pb acetate in drinking water; a Pb-TQ group, which was cotreated with Pb plus TQ (5 mg/kg/day, per os); and a TQ group receiving only TQ. All treatments were applied for five weeks. Results TQ alone did not induce any significant changes in the antioxidant defense system. By contrast, Pb exposure significantly decreased reduced glutathione level and superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase activities in the renal tissue. Interestingly, supplementation with TQ significantly improved the affected antioxidant parameters. Conclusion Our data are the first to provide evidence on the protective effect of TQ against Pb-induced renal antioxidant capacity impairment and suggest that this component might be a clinically promising alternative in Pb nephrotoxicity.

A novel mutation in FGD4/FRABIN causes Charcot Marie Tooth disease type 4H in patients from a consanguineous Tunisian family.

Charcot-Marie-Tooth (CMT) disease constitutes a clinically and genetically heterogeneous group of hereditary neuropathies characterized by progressive muscular and sensory loss in the distal extremities with chronic distal weakness, deformation of the feet, and loss of deep tendon reflexes. CMT4H is an autosomal recessive demyelinating subtype of CMT, due to mutations in FGD4/FRABIN, for which nine mutations are described to date. In this study, we describe three patients from a consanguineous Tunisian family, presenting with severe, early onset, slowly progressive, autosomal recessive demyelinating CMT, complicated by mild to severe kyphoscoliosis, consistent with CMT4H. In these patients, we report the identification of a novel homozygous frameshift mutation in FGD4: c.514_515insG; p.Ala172Glyfs*27. Our study reports the first mutation identified in FGD4 in Tunisian patients affected with CMT. It further confirms the important clinical heterogeneity observed in patients with mutations in FGD4 and the lack of phenotype/genotype correlations in CMT4H. Our results suggest that FGD4 should be screened in other early-onset CMT subtypes, regardless of the severity of the phenotype, and particularly in patients of consanguineous descent. In Tunisians, as in other populations with high consanguinity rates, screening of genes responsible for rare autosomal recessive CMT subtypes should be prioritized.

Fenugreek seeds, a hepatoprotector forage crop against chronic AlCl3 toxicity.

BACKGROUND: Having considered how bioavailable aluminium (Al) may affect ecological systems and animals living there, especially cattle, and in search for a preventive dietary treatment against Al toxicity, we aimed to test the protective role of fenugreek seeds against chronic liver injury induced by aluminum chloride (AlCl3) in Wistar rats. RESULTS: Five months of AlCl3 oral exposure (500 mg/kg bw i.g for one month then 1600 ppm via drinking water) caused liver atrophy, an inhibition of aspartate transaminase (AST), alanine transaminase (ALT) and glutamyl transpeptidase (GGT), an enhancement of both lipid peroxidation and lactate dehydrogenase (LDH) activity and an increase of total protein level in liver. Moreover, histopathological and histochemical examinations revealed moderate alterations in the hepatic parenchyma in addition to a disrupted iron metabolism. Co-administration of fenugreek seed powder (FSP) at 5% in pellet diet during two months succeeded to antagonize the harmful effects of AlCl3 by restoring all tested parameters. CONCLUSION: This study highlighted the hepatotoxicity of AlCl3 through biochemical and histological parameters in one hand and the hepatoprotective role of fenugreek seeds on the other hand. Thus this work could be a pilot study which will encourage farmers to use fenugreek seeds as a detoxifying diet supplement for domestic animals.

Assessment of chromosomal aberrations and micronuclei in peripheral lymphocytes from tunisian hospital workers exposed to ionizing radiation.

Epidemiological studies suggest that cytogenetic biomarkers, such as micronuclei (MN) in peripheral blood lymphocytes may predict cancer risk because they indicate genomic instability. The objective of the present study was to evaluate the frequencies of MN and chromosome aberrations (CA) in peripheral blood lymphocytes of hospital workers exposed to ionizing radiation and healthy subjects. The study was conducted using peripheral blood lymphocytes from 30 workers from the radiology department and 30 from the cardiology department. This study included 27 healthy age- and sex-matched individuals as the control group. The assessment of chromosomal damage was carried out by the use of CA and micronucleus assays in peripheral lymphocytes. Our results show that CA and micronucleus frequencies were significantly higher among the exposed groups when compared to controls. Our finding of significant increase of CA and MN frequencies in peripheral lymphocytes in exposed workers indicates a potential cytogenetic hazard due to this exposure. The enhanced chromosomal damage of subjects exposed to genotoxic agents emphasizes the need to develop safety programs.

Erythrocyte antioxidants enzymes imbalance following subcutaneous pyrethroid treatments in rats of different sex.

Permethrin and deltamethrin are insecticides used all over the world in agriculture to control pests. The aim of this work is to investigate the effects of subcutaneous permethrin and/or deltamethrin treatments on erythrocyte antioxidant enzymes activity in rats of different sex. The results obtained show that permethrin decreases SOD and GPx activity in female rats, while it increases SOD activity in male rats. Deltamethrin treatment reduces GPx activity in male rats, while permethrin has a similar effect but only for short time treatments. A catalase activity decrease was observed in both sexes following pyrethroid treatment but when both the pyrethroids were administrated in male rats, the enzyme activity has increased. In conclusion, this study points out for the first time the importance of rat gender on erythrocyte antioxidant enzymes, which are influenced not only by the length and the type of insecticide treatment but importantly by sex.