Mohsen Sakly

Reproductive toxicity of DDT in adult male rats.

The reproductive toxicity of DDT was investigated in adult male rats exposed to 50 and 100 mg/kg body weight (b.wt) day 1 for 10 successive days. Compared with control animals, administration of DDT led to a dose-dependent reduction of testicular weight and the number as well as the percentage of motile spermatozoa in the epididymis. Testicular histological observationsrevealed alsoamarkedloss of gametes in the lumen of seminiferous tubules. In DDT treated rats, the seminal vesicles weights dropped significantly, resulting from a decrease of testosterone production by testes, whereas serum LH and FSH increased after pesticide exposure. This increase of gonadotrophin levels may be related to an impairment of the negative feedback exerted by the steroid on the hypothalamic–pituitary axis. It is concluded that DDT induced adverse effects on male rat fertility by acting directly on the testes and altering the neuroendocrinefunction.

Dysregulation of the hypothalamus-pituitary-adrenal axis predicts some aspects of the behavioral response to chronic fluoxetine: association with hippocampal cell proliferation

In depressed patients, antidepressant resistance has been associated with dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis but the underlying mechanisms are poorly understood. The scope of this study was to try to create HPA-related antidepressant resistance in mice and to investigate adult hippocampal neurogenesis as a putative mechanism of antidepressant resistance. Mice were subjected to a 9 week Unpredictable Chronic Mild Stress (UCMS). After a 2 weeks drug-free period, mice were segregated in two groups, according to the percentage of corticosterone suppression after dexamethasone injection: High suppression (HS) and Low suppression (LS) mice. From the 5th week onwards, fluoxetine at a dose of 15 mg/kg (i.p.) was administered daily and at the end of 8th week, a battery of behavioral tests assessing the emotional, cognitive, and motor aspects of UCMS-induced depressive-like behavior was applied. Results show that fluoxetine-induced antidepressant effects were observed with higher amplitude in HS when compared to LS on various behavioral phenotypes, like coat state, novelty suppression of feeding, splash test and nest test. The same profile was found concerning the immunohistochimical analysis of ki-67 positive cells in the dentate gyrus of the hippocampus, which is a marker of neuronal proliferation, but not for doublecortin labeling. This suggests that the failure of fluoxetine to induce antidepressant effects may be associated to the poor ability of the compound to stimulate cell proliferation in the hippocampus.

Myrtle berry seed aqueous extract inhibits human neutrophil myeloperoxidase in vitro and attenuates acetic acid-induced ulcerative colitis in rats

We aimed in the present study to investigate the protective effect of a myrtle (Myrtus communis L.) berry seed aqueous extract (MBSAE) on acetic acid (AA)-induced colitis in rats as well as the mechanism implicated in this coli-protection. The use of the LC/MS technique allowed us to identify 18 phenolic compounds in the MBSAE. Secondly, we found that the MBSAE inhibited the luminol-amplified chemiluminescence of resting neutrophils and N-formyl-methionylleucyl-phenylalanine (fMLF) or phorbolmyristate acetate (PMA) stimulated neutrophils in a dose-dependent manner. The MBSAE had no effect on superoxide anions, but it inhibited H2O2 production in the cell free system stimulated with horseradish peroxidase (HRPO) and MPO release from the neutrophils. In vivo, the pre-treatment of rats with sulfasalazine (100 mg kg−1) and the MBSAE (25, 50, and 100 mg kg−1) significantly reduced AA-induced colonic mucosa lesions as well as histopathological changes. The MBSAE counteracted AA-induced lipid peroxidation and the depletion of the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). We also found that the myrtle extract inhibited the increase of the plasma scavenging activity (PSA) and preserved the content of non-enzymatic antioxidants such as sulfhydryl groups (–SH) and reduced glutathione (GSH). More importantly, acetic acid administration increased colonic hydrogen peroxide (H2O2), free iron and calcium levels, while the MBSAE pre-treatment reversed all intracellular mediator perturbations. In conclusion, our data suggests that the MBSAE exerted a potential protective effect against AA-induced injury and oxidative stress in the rat colon. This coli-protection might be related in part to its antioxidant and ROS scavenging activities or by negatively regulating Fenton reaction components such as H2O2 and free iron, which are known to lead to cytotoxicity mediated by intracellular calcium deregulation.

Successful pregnancies after using immotile spermatozoa from ejaculate, epididymis and testis

OBJECTIVE To assess the efficacy of intracytoplasmic sperm injection (ICSI) in term of pregnancy rate with immotile spermatozoa from ejaculate, epididymis and testis. STUDY DESIGN A retrospective study was conducted between January 1998 and March 2001. We performed intracytoplasmic sperm injection with immotile spermatozoa, in 160 couples during 172 cycles. RESULTS The birth rate per cycle was 38.4% in immotile spermatozoa from ejaculate, 35.4% from testis and 38.7% from epididymis. CONCLUSION This retrospective analysis shows that immotile spermatozoa retrieved from epididymis or testicle gives similar fertilization and pregnancies rates as immotile spermatozoa from ejaculate.

Effects of zinc oxide nanoparticles and/or zinc chloride on biochemical parameters and mineral levels in rat liver and kidney

The aim of this study was to assess the potential subacute toxicity of zinc oxide (ZnO) nanoparticles (NPs) in Wistar rats in comparison with reference toxicant, zinc chloride (ZnCl2), of a non-nanoparticulate form. We therefore studied the relationships between zinc (Zn) accumulation, liver and kidney trace element levels, and plasmatic biochemical parameters. Rats in all groups were treated by intraperitoneal injection of ZnO NPs and/or ZnCl2 solution (25 mg/kg) every other day for 10 days. The contents of trace element in the liver and kidney were slightly modulated after ZnO NPs and/or ZnCl2 solution exposure. The same treatment increased the aspartate aminotransferase activity and uric acid concentration. However, ZnO NPs or ZnCl2 solution decreased the creatinine levels, whereas the combined intake of ZnO NPs and ZnCl2 decreased the glucose concentration. Interestingly, the analysis of the lyophilized powder of liver using the x-ray diffractometer showed the degradation of ZnO NPs in ZnO-treated group, instead there is a lack of NPs ZnO biosynthesis from the ZnCl2 solution injected in rats. These investigations suggest that combined injection of ZnO NPs and ZnCl2 solution has a possible toxic effect in rats. This effect could be related to Zn2+ ion release and accumulation of this element in organs. Our findings provide crucial information that ZnO appeared to be absorbed in the organs in an ionic form rather than in a particulate form.

Differential control of MMP and t-PA/PAI-1 expressions by sympathetic and renin-angiotensin systems in rat left ventricle.

In the present study, we tested the hypothesis that angiotensin II (Ang II) has both direct (via AT1 receptors) and indirect (via sympathostimulator pathway) actions on the synthesis and activity of the enzymes involved in the extracellular matrix degradation in vivo. For this purpose, sympathectomy and blockade of the Ang II receptor AT1 were performed alone or in combination in normotensive rats. The mRNA of the plasminogen activator (t-PA) and its inhibitor (PAI-1), the mRNA, protein and activity of the matrix metalloproteinases MMP-2 and MMP-9 were examined by Q-RT-PCR, immunoblotting and zymographic methods in the left ventricle. t-PA and PAI-1 mRNA were decreased after sympathectomy and remained unchanged after AT1 receptors blockade. mRNA was increased for t-PA and decreased by similar degree for PAI-1 after double treatment. MMPs mRNA and protein levels were decreased either after sympathectomy or AT1 receptors blockade and an additive effect was acquired after double treatment. MMPs activity was decreased by similar degree in the three treated groups. Deducted interpretations from our experimental approach suggest that Ang II inhibits directly (via AT1 receptors) and indirectly (via sympathostimulator pathway) t-PA mRNA synthesis. It seems unable to influence directly PAI-1 mRNA, but stimulates indirectly PAI-1 mRNA synthesis. Ang II stimulates directly (via AT1 receptors) and indirectly (via sympathostimulator pathway) MMPs synthesis at both transcriptional and protein levels. The enzymatic activity of MMPs does not seem to be influenced directly by Ang II but it could be stimulated indirectly (via sympathostimulator pathway).

Effects of acute exposure to WIFI signals (2.45GHz) on heart variability and blood pressure in Albinos rabbit.

Electrocardiogram and arterial pressure measurements were studied under acute exposures to WIFI (2.45GHz) during one hour in adult male rabbits. Antennas of WIFI were placed at 25cm at the right side near the heart. Acute exposure of rabbits to WIFI increased heart frequency (+22%) and arterial blood pressure (+14%). Moreover, analysis of ECG revealed that WIFI induced a combined increase of PR and QT intervals. By contrast, the same exposure failed to alter maximum amplitude and P waves. After intravenously injection of dopamine (0.50ml/kg) and epinephrine (0.50ml/kg) under acute exposure to RF we found that, WIFI alter catecholamines (dopamine, epinephrine) action on heart variability and blood pressure compared to control. These results suggest for the first time, as far as we know, that exposure to WIFI affect heart rhythm, blood pressure, and catecholamines efficacy on cardiovascular system; indicating that radiofrequency can act directly and/or indirectly on cardiovascular system.

Postnatal development and behavior effects of in-utero exposure of rats to radiofrequency waves emitted from conventional WiFi devices

The present work investigated the effects of prenatal exposure to radiofrequency waves of conventional WiFi devices on postnatal development and behavior of rat offspring. Ten Wistar albino pregnant rats were randomly assigned to two groups (n=5). The experimental group was exposed to a 2.45GHz WiFi signal for 2h a day throughout gestation period. Control females were subjected to the same conditions as treated group without applying WiFi radiations. After delivery, the offspring was tested for physical and neurodevelopment during its 17 postnatal days (PND), then for anxiety (PND 28) and motricity (PND 40-43), as well as for cerebral oxidative stress response and cholinesterase activity in brain and serum (PND 28 and 43). Our main results showed that the in-utero WiFi exposure impaired offspring neurodevelopment during the first seventeen postnatal days without altering emotional and motor behavior at adult age. Besides, prenatal WiFi exposure induced cerebral oxidative stress imbalance (increase in malondialdehyde level (MDA) and hydrogen peroxide (H2O2) levels and decrease in catalase (CAT) and superoxide dismutase (SOD) activities) at 28 but not 43days old, also the exposure affected acethylcolinesterase activity at both cerebral and seric levels. Thus, the current study revealed that maternal exposure to WiFi radiofrequencies led to various adverse neurological effects in the offspring by affecting neurodevelopment, cerebral stress equilibrium and cholinesterase activity.

Human neutrophils ROS inhibition and protective effects of Myrtus communis leaves essential oils against intestinal ischemia/reperfusion injury

The aim of the present work was to investigate the mechanism implicated in the protective effects of Myrtus communis leaves essential oils (MCEO) on human neutrophils reactive oxygen species (ROS) production. We also studied its preventive effect against intestinal ischemia reperfusion (IIR)-induced oxidative stress in rat model. Essential oils were obtained from the plant leaves by hydrodistillation and analyzed by GC-MS. Neutrophils were isolated from whole human blood using ficoll–dextran method. ROS generation and H2O2 production were measured by luminol-amplified chemiluminescence. The cytochrome c reduction assay was used for superoxide anion determination and Western blotting analysis was to determine the neutrophils myeloperoxidase (MPO) expression. Rats were divided into four groups: control (C), intestinal IR (IIR), MCEO, and MCEO plus IIR. Animals were pretreated with MCEO (50 mg kg−1) during 7 days. IIR was produced by 75 min of intestinal ischemia followed by reperfusion for 120 min. The GC-MS analysis, allowed to the identification of twenty five bioactive compounds in MCEO. In vitro, we found that MCEO inhibited ROS and H2O2 production and attenuated the neutrophils MPO expression. In vivo, the MCEO administration counteracted IIR-induced small intestine, lung and liver lipid peroxidation as well as the depletion of antioxidant enzymes activities such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). MCEO pretreatment also corrected IIR-induced non-enzymatic antioxidants levels depletion such as sulfhydryl groups (–SH) and reduced glutathione (GSH). More importantly, IIR was accompanied by H2O2, free iron and calcium increase while MCEO administration reversed all intracellular mediator perturbations. In conclusion, we suggest that MCEO had a potential protective role against intestinal IR injury, in part owing to its antioxidant potential and ROS scavenging activities.

Role of gastrointestinal motility inhibition and antioxidant properties of myrtle berries (Myrtus communis L.) juice in diarrhea treatment

INTRODUCTION The myrtle (Myrtus communis) belongs to the Myrtaceae family; it is one of the central plants as part of the list of medicinal plants in the Tunisian Pharmacopoeia. Myrtle berry was used for its astringent, tonic, and antiseptic properties, to treat diarrhea, hemorrhoids, and gastrointestinal injury. METHODS Adult male wistar rats were used to evaluate the normal gastro-intestinal transit and gastric emptying as well as castor oil-induced diarrhea, enteropooling tests, and small intestine oxidative stress. The effect of myrtle berries juice (MBJ) (5 and 10ml/kg, bw. p.o.) was after compared to the loperamide and clonidine effects. RESULTS MBJ significantly and dose-dependently inhibited the intestinal motility and gastric emptying. We also found that MBJ administration induced a significant dose-dependent protection against diarrhea and intestinal fluid accumulation. Castor oil-induced intestinal hypersecretion was accompanied by an oxidative stress status in the intestine, which was attenuated by MBJ administration. CONCLUSION We suggest that MBJ had a potent protective effects against castor oil-induced diarrhea in part due, to its antioxidant and antisecretory properties.