The feasibility and outcome of laparoscopic vesicovaginal fistula repair as a minimally invasive technique: a retrospective descriptive monocentric study.

Introduction: vesicovaginal fistula (VVF) is the most common type of urogenital fistula. The laparoscopic approach to VVF repair offers the advantage of minimally invasive surgery with similar principles to the open trans-abdominal approach. The purpose of our study was to evaluate the transperitoneal laparoscopic approach as a minimally invasive tool for VVF repair. Methods: this was a retrospective study including 14 patients with VVF who underwent transperitoneal laparoscopic fistula repair between 2016 and 2020 in the urology department of the university hospital, Kairouan. Patients had undergone surgery at least six months after their primary gynecological surgery and were followed during 9 months after laparoscopic fistula repair. Data regarding patients' characteristics, operative data, and outcomes were gathered. The main outcome was the success rate of VVF closing and postoperative complications. Results: fourteen patients were included. The patient's mean age was 34.8±8.2years. Size of fistula varied from 0.5 to 2cm and all the VVF were supratrigonal. The mean operative time was 145±23.4 minutes with no significant blood loss. The mean hospital stay was 4±1.4 days without major complications. Regarding analgesia, paracetamol was used for the first two days to meet the analgesia needs of all patients, and morphine was used in three cases (21.4%). During follow-up, two patients were re-operated for early recurrence (14.2%) and the total success rate was 85.7% (12 patients). Conclusion: the laparoscopic repair of VVF is a safe, effective, minimally invasive procedure, and without major complications.

Aluminum induced oxidative stress, astrogliosis and cell death in rat astrocytes, is prevented by curcumin.

Aluminum (Al) is recognized potent neurotoxic metal, which causes oxidative stress leading to intracellular accumulation of reactive oxygen species (ROS) and neuronal cell death in various neurodegenerative diseases. Among several medicinal plants with beneficial effects on health, curcumin acts as a multi-functional drug with antioxidant activity. Thus, the purpose of the present study was to evaluate the protective effect of curcumin against aluminum induced-oxidative stress and astrocytes death, in vitro ad in vivo. Incubation of cultured rat astrocytes with two concentrations of Al (37 µM and 150 µM) for 1 h provoked a dose-dependent reduction of the number of living cells as evaluated by Fluorescein diacetate and lactate dehydrogenase assay. Al-treated cells exhibited a reduction of both superoxide dismutase (SOD) and catalase activities. Pretreatment of astrocytes with curcumin (81 µM) prevented Al-induced cell death. Regarding in vivo study, rats were exposed acutely during three consecutive days to three different doses of Al (25 mg/kg, 50 mg/kg and 100 mg/kg, i.p injection), together with curcumin treatment (30 mg/kg). For the chronic model, animals were exposed to Al (3 g/l) in drinking water from intrauterine age to 4 months ages, plus curcumin treatment (175 mg/kg). Data showed that both acute and chronic Al intoxication induced an obvious astrogliosis within motor cortex and hippocampus, while, such effects were restored by curcumin. We showed herein that Al was highly toxic, induced astrocytes death. Then, curcumin protected astrocytes against Al-toxicity. The cytoprotective potential of curcumin is initiated by stimulation of endogenous antioxidant system.

Neuroprotective benefits of grape seed and skin extract in a mouse model of Parkinson's disease.

Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta, and it involves oxidative stress. Our goal was to evaluate the neuroprotective effect of Vitis vinifera red grape seed and skin extract (GSSE) in a model of Parkinson's disease. GSSE is very rich in phenolic compounds, such as flavonoids, anthocyanins, catechins and stilbenes, which are present in the pulp, seeds, and leaves of the fruit. GSSE is known for its antioxidant properties and has shown beneficial effects against oxidative injury in different organs, such as the kidneys, liver, heart and brain. In this study, we revealed the neuroprotective effect of GSSE on midbrain dopaminergic neurons both in vitro and in vivo. We used the neurotoxin 6-hydroxydopamine (6-OHDA), which induces oxidative damage and mimics the degeneration of dopaminergic neurons observed in Parkinson's disease. We found that GSSE was effective in protecting dopamine neurons from 6-OHDA toxicity by reducing apoptosis, the level of reactive oxygen species (ROS) and inflammation. Furthermore, we found that GSSE treatment efficiently protected against neuronal loss and improved motor function in an in vivo 6-OHDA model of Parkinson's disease (PD). Altogether, our results show that GSSE acts at multiple levels to protect dopamine neurons from degeneration in a model of PD.

Improvement of Diabetes Symptoms and Complications by an Aqueous Extract of Linum usitatissimum (L.) Seeds in Alloxan-Induced Diabetic Mice.

Although progress has been made to show the role of raw flaxseed and flaxseed extracts in health promotion, identification of mechanism(s) of action and molecule(s) underpinning beneficial effects largely remain unknown. The present study evaluated the efficacy of an aqueous flaxseed extract (AFE) to correct alloxan-induced diabetes in mice. Mice were divided into five groups: one nondiabetic (negative control) and four diabetic. Diabetic mice were treated with AFE, gallic acid (GA) (major component of AFE), insulin (positive control), or remained untreated (positive control). Oral administration of AFE strongly improved serum glucose, oral glucose tolerance, insulin tolerance, body weight, and polyphagia in diabetic mice. AFE was effective in controlling lipid peroxidation (thiobarbituric acid-reactive substances) and antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase) in liver and kidney, which undergo diabetes-related complications due to hyperglycemia. These results demonstrated that GA alone was sufficient to account for the beneficial health effects of AFE against diabetes.

Protective role of vitamin E against cadmium induced oxidative stress into the rat liver.

INTRODUCTION: Cadmium (Cd) is a toxic heavy metal used in various industrial applications and therefore can cause, both by environmental or professional exposure, several damage in all body systems. The present study was developed to determine the toxic effect of high dose of Cd on the rat's liver as well as the putative protective effect of vitamin E. METHODS: During the experiment, rats were administrated Cd per orally (PO) (15mg/Kg bw) alone or associated with an intraperitonial (IP) injection of alphatocopherol (Vitamin E) (300mg/Kg / day) for three weeks. We analyzed the effect of vitamin E on Cd induced liver remodeling by hematoxylin-eosin staining (HE), and by the determination of the antioxidant profiles and lipid peroxidation in rats's livers. RESULTS: Data confirmed that high dose of cd induced a loss of the liver weight and a pro-oxidative state into hepatocytes characterized by increased malondialdehyde (MDA) and peroxidase (POD), no changes in catalase (CAT) and a decrease on the superoxide dismutase (SOD) activities. These disturbances may be explained by a decrease in the level of hepatic calcium (Ca). Co-treatment with Vitamin E, decreased MDA and POD activities, increased CAT and SOD activities and restored Ca level. All these corrections were accompanied by an improvement of the liver 's structure. CONCLUSION: Our results suggest that Cd induced an oxidative stress into rat liver and Vitamin E exerted antioxidant properties which can be mediated by the modulation of Ca level.

Human peroxidasin 1 promotes angiogenesis through ERK1/2, Akt, and FAK pathways.

Aims: The term angiogenesis refers to sprouting of new blood vessels from pre-existing ones. The angiogenic process involves cell migration and tubulogenesis requiring interaction between endothelial cells and the extracellular matrix. Human peroxidasin 1 (hsPxd01) is a multidomain heme peroxidase found embedded in the basement membranes. As it promotes the stabilization of extracellular matrix, we investigated its possible role in angiogenesis both in vitro and in vivo. Methods and results: We analysed the effects of peroxidasin 1 gene silencing and supplementation by recombinant hsPxd01 in TeloHAEC endothelial cells on cell migration, tubulogenesis in matrigel, and intracellular signal transduction as assessed by kinase phosphorylation and expression of pro-angiogenic genes as measured by qRT-PCR. We further evaluated the angiogenic potential of recombinant peroxidasin in a chicken chorioallantoic membrane model. RNA silencing of endogenous hsPxd01 significantly reduced tube formation and cell migration, whereas supplementation by the recombinant peroxidase promoted tube formation in vitro and stimulated vascularization in vivo through its catalytic activity. Moreover, recombinant hsPxd01 promoted phosphorylation of Extracellular signal-Regulated Kinases (ERK1/2), Protein kinase B (Akt), and Focal Adhesion Kinase (FAK), and induced the expression of pro-angiogenic downstream genes: Platelet Derived Growth Factor Subunit B (PDGFB), endothelial-derived Heparin Binding EGF-like growth factor (HB-EGF), CXCL-1, Hairy-Related Transcription Factor 1 (HEY-1), DNA-binding protein inhibitor (ID-2), Snail Family Zinc Finger 1 (SNAI-1), as well as endogenous hsPxd01. However, peroxidasin silencing significantly reduced Akt and FAK phosphorylation but induced ERK1/2 activation after supplementation by recombinant hsPxd01. While hsPxd01 silencing significantly reduced expression of HEY-1, ID-2, and PDGFB, it did not affect expression of SNAI-1, HB-EGF, and CXCL-1 after supplementation by recombinant hsPxd01. Conclusion: Our findings suggest a role of enzymatically active peroxidasin 1 as a pro-angiogenic peroxidase and a modulator of ERK1/2, Akt and FAK signalling.

Neoplasm of a supernumerary undescended testis: A case report and review of the literature.

INTRODUCTION: Polyorchidism, defined as the presence of more than two testicles, is a rare congenital abnormality of the male genital tract. There is no consensus regarding the management of supranumerary testis (SNT) due to its rareness. To the best of our knowledge, this is the first report of leiomyoma in SNT. PRESENTATION OF CASE: We report the case of a 41-year-old man with two right testes sharing a common vas deferens and separate epididymides. Orchiectomy of right testes was performed. Pathology examination found that the superior testis was the site of a leiomyoma and the lower tesits was the site of an intratubular germ cell neoplasia (IGCN). Orchiopexy and biopsy were later performed for the left testis. Histology was compatible with IGCN. We opted for follow-up to avoid risks of hypogonadism. DISCUSSION: Polyorchidism is usually asymptomatic and found incidentally during surgery for inguinal hernia, undescended testes as in our case, torsion, hydrocele or testicular tumor. If the SNT is scrotal, and there is no other indication for surgery, most authors recommend conservative management with regular ultrasound follow-up. If nonscrotal SNT is found incidentally during surgery, orchiectomy could be performed because of increased risk of malignancy. Treatment of IGCN includes surveillance, orchiectomy, or low-dose external radiation. CONCLUSION: Different factors come into account for polyorchidsm management: the drainage system, the fertile potential of the supernumerary gonad, and its localization. In cases of uncomplicated polyorchidism, a conservative treatment, with US or MRI follow-up seems to be a rational choice without surgical complications.

Preventive effect of ethanolic extract of cactus (Opuntia ficus-indica) cladodes on methotrexate-induced oxidative damage of the small intestine in Wistar rats.

CONTEXT: Methotrexate (MTX) is a cytotoxic chemotherapeutic element for various inflammatory diseases. The cytotoxic effect of MTX is also seen in normal tissues having a high proliferation rate including gastrointestinal and bone marrow. AIMS: The aim of this study was to find out whether oxidative damage could be relevant for MTX-induced toxicity in vivo using Wistar rats and to investigate the preventive potential of cactus cladodes. MATERIALS AND METHODS: Adult and healthy male Wistar rats (200-250 g) were pretreated by ethanol fraction of cactus cladodes. Following a single dose of MTX (20 mg/kg), either vehicle (saline) or ethanolic (400 mg/kg) was administered intraperitoneally. All animals were killed 24 h after the intraperitoneal injection of MTX. Small intestine samples were collected for malondialdehyde (MDA) level, protein carbonyl generation, and peroxidase and catalase (CAT) activity measurement. The small intestine was also collected for histopathology analysis. STATISTICAL ANALYSIS USED: Each experiment was conducted in triplicate separately. Values were presented as a mean ± standard deviation. Differences were considered significant at P < 0.05. RESULTS: Our results showed that MTX-induced significant alterations in oxidative stress markers noticed in the form of intestinal tissues damage, MDA level increased and protein carbonyls generation. CAT and peroxidase activities decreased with MTX administration. The combined treatment of MTX with cactus extracts showed a reduction of MTX-induced oxidative damage. CONCLUSIONS: It could be concluded that cactus cladodes extract was effective in protecting the small intestine against MTX-induced damage.

Cigarette smoke extract interferes with placenta macrophage functions: A new mechanism to compromise placenta functions?

The success of pregnancy depends on the maternal immune system's ability to promote tolerance and host defense. This equilibrium is compromised in inflammatory and infectious impairment of placenta. Smoking during pregnancy exposes the fetus to severe complications which might result from an alteration in placenta macrophages (pMφ) functions. In this study, we assessed the effect of cigarette smoke extract (CSE) on the functions of third trimester pMφs.CSE inhibited particles uptake and the formation of multinucleated giant cells, a recently reported property of pMφs based on their ability to fuse in vitro. These alterations were associated with a CSE-induced abnormal activation of pMφs, which was characterized by an increased release of TNF, interleukin (IL)-33, and decreased IL-6 and IL-10 release. Furthermore, CSE enhanced the expression of metalloproteinase genes known to be involved in tissue remodeling. This effect of CSE on pMφs was specific because CSE affected circulating monocytes in a different way. Finally, we showed that nicotine affected in part the functional properties of pMφs. Taken together, these results showed that CSE modulated the functional activity of pMφs, which may compromise pregnancy.

Contribution of oxidative stress in acute intestinal mucositis induced by 5 fluorouracil (5-FU) and its pro-drug capecitabine in rats.

This study was designed to examine the contribution of oxidative stress in gastrointestinal disorders after an intraperitoneal administration of 5 fluorouracil (5-FU; 100 mg/kg of body weight (b.w.)) and capecitabine oral administration (500 mg/kg b.w.). The animals were divided into three groups: Group A (NaCl,10 ml/kg of b.w.) considered as control group, group B was intoxicated by 5-FU and group C was the group of animals treated with capecitabine (CAP). To evaluate the secretory and enteropooling effects, we used magnesium sulfate (MgSO4), 1 ml/100 g of b.w. as a hypersecretion agent . The mucosal gastro-intestinal specimens were scraped and examined for biological markers of oxidative stress and intracellular mediators. These anticancer drugs caused many intestinal damages manifested by an elevation of fluid accumulation and imbalance in electrolytes secretion. The intestinal tissues from treated rats not only showed a significant increase in malondialdehyde (MDA), protein carbonylation and hydrogen peroxide (H2O2) production. but also showed a significant depletion of enzymatic and non-enzymatic antioxidant, such as, glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and sulfhydryl groups (-SH). These effects were related with histopathological damage and a perturbation of intracellular mediators. As expected, these disturbances were observed in the group of rats poisoned by the MgSO4. Data suggest the contribution of oxidative stress in chemotherapy-induced many disorders in intestinal tract.

Neuroprotective effects of the gliopeptide ODN in an in vivo model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopamine (DA) neurons through apoptotic, inflammatory and oxidative stress mechanisms. The octadecaneuropeptide (ODN) is a diazepam-binding inhibitor (DBI)-derived peptide, expressed by astrocytes, which protects neurons against oxidative cell damages and apoptosis in an in vitro model of PD. The present study reveals that a single intracerebroventricular injection of 10 ng ODN 1 h after the last administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) prevented the degeneration of DA neurons induced by the toxin in the substantia nigra pars compacta of mice, 7 days after treatment. ODN-mediated neuroprotection was associated with a reduction of the number of glial fibrillary acidic protein-positive reactive astrocytes and a strong inhibition of the expression of pro-inflammatory genes such as interleukins 1ß and 6, and tumor necrosis factor-α. Moreover, ODN blocked the inhibition of the anti-apoptotic gene Bcl-2, and the stimulation of the pro-apoptotic genes Bax and caspase-3, induced by MPTP in the substantia nigra pars compacta. ODN also decreased or even in some cases abolished MPTP-induced oxidative damages, overproduction of reactive oxygen species and accumulation of lipid oxidation products in DA neurons. Furthermore, DBI knockout mice appeared to be more vulnerable than wild-type animals to MPTP neurotoxicity. Taken together, these results show that the gliopeptide ODN exerts a potent neuroprotective effect against MPTP-induced degeneration of nigrostriatal DA neurons in mice, through mechanisms involving downregulation of neuroinflammatory, oxidative and apoptotic processes. ODN may, thus, reduce neuronal damages in PD and other cerebral injuries involving oxidative neurodegeneration.

Vinblastine, an anticancer drug, causes constipation and oxidative stress as well as others disruptions in intestinal tract in rat.

The purpose of this study is to examine the gastrointestinal disorders after injection of vinblastine (2 mg kg-1 b.w. i.v.) in rats. Animals were divided into two equal groups: Group 1 was considered as a control group (NaCl, 0.9%). Group 2 was treated with intravenous injection of vinblastine for 7 days. Loperamide (2 mg kg-1) was injected in a saline solution subcutaneously to induce constipation in another group of rats during the same period. Fecal parameters of the different groups have been determined. At the end of the experiment, animals were anaesthetized and sacrificed by decapitation. The intestinal mucosa specimens were examined for lipid peroxidation, sulfhydryl groups (-SH) and protein carbonylation as well as antioxidant enzyme activities and intracellular mediators. Gastrointestinal motility was realized by the test meal (10% charcoal in 5% gum arabic). In result, statistically significant decreases in the fecal number and water content collected during 24 h were detected in the vinblastine group, but less important than loperamide control group. The animals treated with vinblastine, showed also a significant decrease (13%) of GIT, lower than that of loperamide (34%). The intestinal tissues from vinblastine-treated rats were showed a significant increase in lipoperoxydation and H2O2 production as well as a significant depletion of enzymatic and non-enzymatic antioxidants. Added to that, a disruption of intracellular iron and calcium levels was observed. Therefore, the present study provide the first strong evidence that vinblastine induced numerous disruptions in gastrointestinal which are related to oxidative stress and intracellular mediators disorders.

Chemical constituents and pharmacological actions of carob pods and leaves (Ceratonia siliqua L.) on the gastrointestinal tract: A review.

Carob tree, Ceratonia siliqua L., is a medicinal plant used in Tunisian traditional medicine for the treatment of the gastro-intestinal (GI) disorders. In this respect, a relatively large number of scientific publications on the carob tree have been published in recent years. Therefore, the present review was aimed to analyze the traditional uses, phytochemical constituents and pharmacological activities of Ceratonia siliqua on the GI tract. Indeed, previous investigations on the carob pods and leaves have revealed the presence of a number of compounds including high amounts of carbohydrates, dietary fibers, minerals, polyphenols, flavonoids and low amounts of protein and lipids. This plant possesses anti-inflammatory, antimicrobial, anti-diarrheique, antioxidant, anti-ulcer, anti-constipation and anti-absorptive of glucose activities in the gastrointestinal tract. Based on the chemical and pharmacological characteristics of C. siliqua, we concluded that this species has beneficial preventive and therapeutic properties, especially, in digestive tract.

Brain proteomic modifications associated to protective effect of grape extract in a murine model of obesity.

In recent years, the obesity epidemic has developed into a major health crisis worldwide. With current treatments limited to expensive, high-risk surgery and minimally efficacious pharmacotherapy, new therapeutic options are urgently needed to fight against this alarming trend. Though brain dysfunction has been studied linked to high fat diet (HFD) and grape seed and skin extract (GSSE) correction, the proteomic modifications linking the two effects on brain lipotoxicity are not well understood. To this end rats were exposed for 8 weeks to HFD treatment, to GSSE (500mg/kg BW) and to binary mixture of HFD and GSSE to gain insight into the potential pathways altered with metabolic disease and the protection afforded by GSSE. Significant modifications of brain proteins were detected using mass spectrometry-based differential proteomics. These proteins were mainly related to oxidative stress, glycolysis and calcium signaling. Additionally, proteins involved in the cytoskeleton were also affected by HFD treatment. Interestingly, whether up- or down regulated protein abundances, GSSE corrected most of the disturbances of HFD treatment. These findings provide impetus for future therapeutic investigation on GSSE against other metabolic disorders.

Prenatal exposure to cigarette smoke enhances oxidative stress in astrocytes of neonatal rat.

Oxidative stress is involved in the pathogenesis of smoking-related disease. Protection of astrocytes from oxidative insult appears essential to maintain brain function. In this study, we have investigated the effect of gestational cigarette exposure on astrocyte survival. Pregnant female were randomly allocated to the control group or to the cigarette smoke group in which they were placed in an exposure chamber and inhale three cigarettes smoke twice a day for a period of 20 days. The control group was kept in the exposure chamber for the same duration, but without exposure to cigarette smoke. Newborn rats from both groups were weighed 24 h after birth and then cerebral hemispheres were collected for astrocyte culture. Incubation of astrocytes isolated from animals exposed to cigarette smoke with 300 µM H2O2 for 1 h induced a significant decrease of the proportion of surviving cells compared to cells isolated form control animals. We have observed that H2O2-treated astroglial cells derived from cigarette smoke exposure showed more reduced superoxide dismutase and catalase activities than H2O2-treated astroglial cells from control animals. In conclusion, this study indicates that astroglial cells derived from newborn rats exposed in utero to cigarette smoke are more vulnerable to oxidative assault than cultured astrocytes obtained from control animals. These results point out the existence of excitotoxic lesions in newborn exposed in utero to cigarette smoke and suggest that despite their high antioxidative activities, astrocytes cannot survive and protect neurons under massive oxidative stress.

Involvement of endogenous antioxidant systems in the protective activity of pituitary adenylate cyclase-activating polypeptide against hydrogen peroxide-induced oxidative damages in cultured rat astrocytes.

Astroglial cells possess an array of cellular defense mechanisms, including superoxide dismutase (SOD) and catalase antioxidant enzymes, to prevent damages caused by oxidative stress. Nevertheless, astroglial cell viability and functionality can be affected by significant oxidative stress. We have previously shown that pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent glioprotective agent that prevents hydrogen peroxide (H2 O2 )-induced apoptosis in cultured astrocytes. The purpose of this study was to investigate the potential protective effect of PACAP against oxidative-generated alteration of astrocytic antioxidant systems. Incubation of cells with subnanomolar concentrations of PACAP inhibited H2 O2 -evoked reactive oxygen species accumulation, mitochondrial respiratory burst, and caspase-3 mRNA level increase. PACAP also stimulated SOD and catalase activities in a concentration-dependent manner, and counteracted the inhibitory effect of H2 O2 on the activity of these two antioxidant enzymes. The protective action of PACAP against H2 O2 -evoked inhibition of antioxidant systems in astrocytes was protein kinase A, PKC, and MAP-kinase dependent. In the presence of H2 O2 , the SOD blocker NaCN and the catalase inhibitor 3-aminotriazole, both suppressed the protective effects of PACAP on SOD and catalase activities, mitochondrial function, and cell survival. Taken together, these results indicate that the anti-apoptotic effect of PACAP on astroglial cells can account for the activation of endogenous antioxidant enzymes and reduction in respiration rate, thus preserving mitochondrial integrity and preventing caspase-3 expression provoked by oxidative stress. Considering its powerful anti-apoptotic and anti-oxidative properties, the PACAPergic signaling system should thus be considered for the development of new therapeutical approaches to cure various pathologies involving oxidative neurodegeneration. We propose the following cascade for the glioprotective action of Pituitary adenylate cyclase-activating polypeptide (PACAP) against H2 O2 -induced astrocyte damages and cell apoptosis in cultured rat astrocytes. PACAP, through activation of its receptor, PAC1-R, and the protein kinase A (PKA), protein kinase C (PKC), and MAP-kinases signaling pathways, prevents accumulation of ROS and inhibition of SOD and catalase activities. This allows the preservation of mitochondrial membrane integrity and the reduction in caspase-3 activation induced by H2 O2 . These data may lead to the development of new strategies for cerebral injury treatment. Cat, catalase; Cyt. C, cytochrome C; SOD, superoxide dismutase.

Efficacy of grape seed and skin extract against doxorubicin-induced oxidative stress in rat liver.

Doxorubicin (Dox) is an anthracycline used in chemotherapy, although it causes toxicity and oxidative stress. Grape seed and skin extract (GSSE) is a mixture of polyphenolic compounds with antioxidant properties. To evaluate the hepato-toxicity of Dox on healthy rats as well as the protective effect of GSSE, rats were treated with GSSE (500mg/kg bw) during 8 days. At the 4th day of treatment, they received a single dose of Dox (20 mg/kg bw). After the treatment (9th day), livers were collected and processed for oxidative stress status. Dox increased MDA (+ 900%), decreased catalase (-60%) and increased peroxidase (+90%) and superoxide dismutase (+100%) activities. In this latter case Dox mainly increased the iron isoform. Furthermore Dox altered intracellular mediators as catalytic free iron (-75%), H2O2(-75%) and calcium (+30%). Dox also affected liver function by elevating plasma triacylglycerol and transaminases and liver morphology by altering its typical architecture. Importantly all Dox-induced liver disturbances were alleviated upon GSSE treatment. Dox induced liver toxicity and an oxidative stress mainly characterized by increased lipoperoxidation but not protein carbonylation. GSSE efficiently protected the liver from Dox-induced toxicity and appeared as a safe adjuvant that could be incorporated into chemotherapy protocols.

Dietary supplement enriched in antioxidants and omega-3 protects from progressive light-induced retinal degeneration.

In the present study, we have evaluated one of the dietary supplements enriched with antioxidants and fish oil used in clinical care for patient with age-related macular degeneration. Rats were orally fed by a gastric canula daily with 0.2 ml of water or dietary supplement until they were sacrificed. After one week of treatment, animals were either sacrificed for lipid analysis in plasma and retina, or used for evaluation of rod-response recovery by electroretinography (ERG) followed by their sacrifice to measure rhodopsin content, or used for progressive light-induced retinal degeneration (PLIRD). For PLIRD, animals were transferred to bright cyclic light for one week. Retinal damage was quantified by ERG, histology and detection of apoptotic nuclei. Animals kept in dim-cyclic-light were processed in parallel. PLIRD induced a thinning of the outer nuclear layer and a reduction of the b-wave amplitude of the ERG in the water group. Retinal structure and function were preserved in supplemented animals. Supplement induced a significant increase in omega-3 fatty acids in plasma by 168% for eicosapentaenoic acid (EPA), 142% for docosapentaenoic acid (DPA) and 19% for docosahexaenoic acid (DHA) and a decrease in the omega-6 fatty acids, DPA by 28%. In the retina, supplement induced significant reduction of linolenic acid by 67% and an increase in EPA and DPA by 80% and 72%, respectively, associated with significant decrease in omega-6 DPA by 42%. Supplement did not affect rhodopsin content or rod-response recovery. The present data indicate that supplement rapidly modified the fatty acid content and induced an accumulation of EPA in the retina without affecting rhodopsin content or recovery. In addition, it protected the retina from oxidative stress induced by light. Therefore, this supplement might be beneficial to slow down progression of certain retinal degeneration.

Comparative analysis of Tunisian wild Crataegus azarolus (yellow azarole) and Crataegus monogyna (red azarole) leaf, fruit, and traditionally derived syrup: phenolic profiles and antioxidant and antimicrobial activities of the aqueous-acetone extracts.

Quantitative and qualitative analyses of the yellow and red azarole phenolic extracts prepared from leaf, fruit peel/pulp, and syrup were comparatively investigated. The yellow azarole was found significantly richer in polyphenols than the red-fruit species. Hyperoside was the main phenolic in both yellow and red azarole leaves and only in yellow fruits, whereas procyanidin B2 was the major compound in red fruits. Yellow azarole leaf and fruit peel extracts exhibited the strongest antioxidant activities using DPPH (≈168 and 79 µmol TEAC/g fw, respectively) and FRAP (≈378 and 161 µmol Fe(2+)/g fw, respectively) assays. The highest antibacterial activities were recorded for the yellow azarole leaf and fruit peel extracts, especially against Staphylococcus aureus and Streptococcus faecalis . The low phenolic content of the syrups contrasted with their significant antioxidant and antimicrobial potentials, which were correlated to their hydroxymethylfurfural (HMF) (furan derivative amounts) content.

The octadecaneuropeptide ODN prevents 6-hydroxydopamine-induced apoptosis of cerebellar granule neurons through a PKC-MAPK-dependent pathway.

Oxidative stress, induced by various neurodegenerative diseases, initiates a cascade of events leading to apoptosis, and thus plays a critical role in neuronal injury. In this study, we have investigated the potential neuroprotective effect of the octadecaneuropeptide (ODN) on 6-hydroxydopamine (6-OHDA)-induced oxidative stress and apoptosis in cerebellar granule neurons (CGN). ODN, which is produced by astrocytes, is an endogenous ligand for both central-type benzodiazepine receptors (CBR) and a metabotropic receptor. Incubation of neurons with subnanomolar concentrations of ODN (10⁻¹8 to 10⁻¹² M) inhibited 6-OHDA-evoked cell death in a concentration-dependent manner. The effect of ODN on neuronal survival was abrogated by the metabotropic receptor antagonist, cyclo1₋8 [DLeu5]OP, but not by a CBR antagonist. ODN stimulated polyphosphoinositide turnover and ERK phosphorylation in CGN. The protective effect of ODN against 6-OHDA toxicity involved the phospholipase C/ERK MAPK transduction cascade. 6-OHDA treatment induced an accumulation of reactive oxygen species, an increase of the expression of the pro-apoptotic gene Bax, a drop of the mitochondrial membrane potential and a stimulation of caspase-3 activity. Exposure of 6-OHDA-treated cells to ODN blocked all the deleterious effects of the toxin. Taken together, these data demonstrate for the first time that ODN is a neuroprotective agent that prevents 6-OHDA-induced oxidative stress and apoptotic cell death.