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.

Vasomodulatory effects of semi-purified fractions of garlic aqueous extract on chick chorioallantoic membrane.

Allium sativum (As), commonly known as garlic, has been used for a long time, for its therapeutic effects. Recent studies showed the ability of As to modulate vascular activity. The present study aimed to investigate the vasomodulatory effects of aqueous extract of As and to analyse the molecular nature of the active components. Experiments were performed on chick chorioallantoic membrane. Fractions of garlic were directly injected using micropipette on a high vessel density area. Our results clearly indicated that garlic increased permeability and induced vasodilatation of blood vessels and capillaries. These effects were dose-dependent and had been observed just few minutes after the onset of treatment. The active component responsible of these effects, which had a low molecular weight seems to be of peptide nature and appeared different from Dially Sulfide (DAS) and Dially Disulfide (DADS).

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.

MARCKS and MARCKS-like proteins in development and regeneration.

BACKGROUND: The Myristoylated Alanine-Rich C-kinase Substrate (MARCKS) and MARCKS-like protein 1 (MARCKSL1) have a wide range of functions, ranging from roles in embryonic development to adult brain plasticity and the inflammatory response. Recently, both proteins have also been identified as important players in regeneration. Upon phosphorylation by protein kinase C (PKC) or calcium-dependent calmodulin-binding, MARCKS and MARCKSL1 translocate from the membrane into the cytosol, modulating cytoskeletal actin dynamics and vesicular trafficking and activating various signal transduction pathways. As a consequence, the two proteins are involved in the regulation of cell migration, secretion, proliferation and differentiation in many different tissues. MAIN BODY: Throughout vertebrate development, MARCKS and MARCKSL1 are widely expressed in tissues derived from all germ layers, with particularly strong expression in the nervous system. They have been implicated in the regulation of gastrulation, myogenesis, brain development, and other developmental processes. Mice carrying loss of function mutations in either Marcks or Marcksl1 genes die shortly after birth due to multiple deficiencies including detrimental neural tube closure defects. In adult vertebrates, MARCKS and MARCKL1 continue to be important for multiple regenerative processes including peripheral nerve, appendage, and tail regeneration, making them promising targets for regenerative medicine. CONCLUSION: This review briefly summarizes the molecular interactions and cellular functions of MARCKS and MARCKSL1 proteins and outlines their vital roles in development and regeneration.

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.

Giant urethral diverticulum calculus revealed by peri-urethral abscess.

Urethral diverticulum of the male is uncommon. We report a case of bulbar urethraldiverticulum with contained giant calculus presenting as left inguino-scrotal swellingsecondary to peri-urethral abscess in a 40 year-old male. In the light of this case Weemphasize the importance of investigation for the presence of urethral diverticulum in youngmale individuals presenting with voiding disturbances to preventrelated complications.

The conversion of glutamate by glutamine synthase in neocortical astrocytes from juvenile rat is important to limit glutamate spillover and peri/extrasynaptic activation of NMDA receptors.

Glutamate transporters (EAATs) are important to maintain spatial and temporal specificity of synaptic transmission. Their efficiency to uptake and transport glutamate into the intracellular space depends on several parameters including the intracellular concentrations of Na+ and glutamate, the elevations of which may slow down the cycling rate of EAATs. In astrocytes, glutamate is maintained at low concentration due to the presence of specific enzymes such as glutamine synthase (GS). GS inhibition results in cytosolic accumulation of glutamate suggesting that the conversion of glutamate by GS is important for EAATs operation. Here we recorded astrocytes from juvenile rat neocortical slices and analyzed the consequences of elevated intracellular glutamate concentrations and of GS inhibition on the time course of synaptically evoked transporter current (STC). In slices from rats treated with methionine sulfoximine (MSO), a GS inhibitor, STC evoked by short burst of high frequency stimulation (HFS; 100 Hz for 100 ms) but not by low frequency stimulation (LFS; 0.1 Hz) was twice slower than STC evoked from saline injected rats. Same results were obtained for astrocytes recorded with pipette containing 3-10 mM glutamate and compared with cells recorded with 0 or1 mM glutamate in the patch pipette. We also showed that HFS elicited significantly larger NMDAR-excitatory postsynaptic currents (EPSCs) with a stronger peri/extrasynaptic component in pyramidal cells from MSO-treated compared with saline treated rats. Taken together our data demonstrate that the conversion of glutamate by GS is fundamental to ensure an efficient clearance of glutamate by EAATs and to prevent glutamate spillover. GLIA 2017;65:401-415.

Neuroglobin protects astroglial cells from hydrogen peroxide-induced oxidative stress and apoptotic cell death.

Oxidative stress, resulting from accumulation of reactive oxygen species, plays a critical role in astroglial cell death occurring in diverse neuropathological conditions. Numerous studies indicate that neuroglobin (Ngb) promotes neuron survival, but nothing is known regarding the action of Ngb in astroglial cell survival. Thus, the purpose of this study was to investigate the potential glioprotective effect of Ngb on hydrogen peroxide (H2 O2 )-induced oxidative stress and apoptosis in cultured mouse astrocytes. Incubation of cells with subnanomolar concentrations of Ngb (10-14 -10-10  M) was found to prevent both H2 O2 -evoked reduction in surviving cells number and accumulation of reactive oxygen species in a concentration-dependent manner. Furthermore, Ngb treatment abolishes H2 O2 -induced increase in mitochondrial oxygen consumption rates. Concomitantly, Ngb treatment rescues H2 O2 -associated reduced expression of endogenous antioxidant enzymes (superoxide dismutases and catalase) and prevents the stimulation of the expression of pro-inflammatory genes (inducible nitric oxide synthase, cyclooxygenase-2, and interleukin (IL) IL-6 and IL-33). Moreover, Ngb blocks the stimulation of Bax (pro-apoptotic) and the inhibition of Bcl-2 (anti-apoptotic) gene expression induced by H2 O2 , which in turn abolishes caspase 3 activation. The protective effect of Ngb upon H2 O2 induced activation of caspase 3 activity and cell death can be accounted for by activation of protein kinase A and mitogen-activated protein kinase transduction cascade. Finally, we demonstrate that Ngb increases Akt phosphorylation and prevents H2 O2 -provoked inhibition of ERK and Akt phosphorylation. Taken together, these data demonstrate for the first time that Ngb is a glioprotective agent that prevents H2 O2 -induced oxidative stress and apoptotic astroglial cell death. Protection of astrocytes from oxidative insult may thus contribute to the neuroprotective effect of Ngb.

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.

Differential Molecular Targets for Neuroprotective Effect of Chlorogenic Acid and its Related Compounds Against Glutamate Induced Excitotoxicity and Oxidative Stress in Rat Cortical Neurons.

The present study has been designed to explore the molecular mechanism and signaling pathway targets of chlorogenic acid (CGA) and its main hydrolysates, caffeic (CA) and quinic acid in the protective effect against glutamate-excitotoxicity. For this purpose 8-DIV cortical neurons in primary culture were exposed to 50 µM L-glutamic acid plus 10 µM glycine, with or without 10-100 µM tested compounds. Chlorogenic acid and caffeic acid via their antioxidant properties inhibited cell death induced by glutamate in dose depended manner. However, quinic acid slightly protects neurons at a higher dose. DCF, JC-1 and Ca2+sensitive fluorescent dye fura-2, were used to measure intracellular ROS accumulation, mitochondrial membrane potential integration and intracellular calcium concentration [Ca2+] i . Results indicate that similarly, CGA acts as a protective agent against glutamate-induced cortical neurons injury by suppressing the accumulation of endogenous ROS and restore the mitochondrial membrane potential, activate the enzymatic antioxidant system by the increase levels of SOD activity and modulate the rise of intracellular calcium levels by increasing the rise of intracellular concentrations of Ca2+caused by glutamate overstimulation. PKC signaling cascade appear to be engaged in this protective mechanism. Interseling, CGA and CA also exhibit antiapoptotic properties against glutamate-induced cleaved activation of pro-caspases; caspase 1,8 and 9 and calpain (PD 150606,Calpeptin and MDL 28170).These data suggest that neuroprotective activity of CGA ester may occurs throught its hydrolysate,the caffeic acid and its interaction with intracellular molecules suggesting that CGA exert its neuroprotection via its caffeoly acid group that might potentially be used as a therapeutic agent in neurodegeneratives disorders associated with glutamate excitotoxicity.

Irinotecan chemotherapy-induced intestinal oxidative stress: Underlying causes of disturbed mucosal water and electrolyte transport.

Irinotecan, a chemotherapy drug, can cause acute diarrhea immediately after administration. Hence, the present study was designed to investigate the gastrointestinal (GI) disturbances after an intraperitoneal (IP) administration of irinotecan in rats.Twenty Wistar rats were separated into two groups of ten. Group A was considered as a control group (NaCl, 0.9%). Group B was treated with irinotecan at a single dose of 200mgkg-1. The rats were observed for defecation. For the enteropooling test, the animals were sacrificed by decapitation 1h post-treatment. The small intestine was excised and the fluid was milked into a graduated tube and the volume was measured. After centrifugation of intraluminal liquid, the electrolyte concentrations in the supernatants were measured by flame photometry. Oxidative stress parameters and intracellular mediators as well as the MPO activity were determined in intestinal mucosa by colorimetric methods Our result indicated that irinotecan produces an intestinal fluid accumulation and electrolyte transport disorders. These effects were associated with augmented intestinal MPO activity and oxidative damage such as an elevation of MDA production and a depletion of enzymatic and non-enzymatic antioxidants. More than that, drug administration provoked intracellular mediator disturbances such as a free iron, H2O2 and calcium levels. In conclusion, the data suggest that irinotecan caused a gastrointestinal stress via oxidative stress-induced disturbances in water and electrolyte transport in the intestinal mucosa in rats.

Ceratonia siliqua L. (immature carob bean) inhibits intestinal glucose absorption, improves glucose tolerance and protects against alloxan-induced diabetes in rat.

BACKGROUND: This study was designed to investigate the effects of immature carob pod aqueous extract (ICPAE) on intestinal glucose absorption in vitro and in vivo using an oral glucose tolerance test (OGTT) as well as the potential antidiabetic effect in alloxan-induced diabetic rats. OGTT was carried by administration of glucose (2 g kg-1 , p.o.) and after treatment with extract (50, 100 and 200 mg kg-1 body weight). Diabetes was induced by single intraperitoneal injection of alloxan (150 mg kg-1 ). However, the extracts at various doses or glibenclamide (GLB, 10 mg kg-1 body weight) were given by oral administration for 2 weeks. RESULTS: ICPAE (50-2000 µg mL-1 ) exerted dose-dependent reduction of sodium-dependent glucose transport across isolated mice jejunum and the maximal inhibition exceeded 50%.The ICPAE treatment improved glucose tolerance. More importantly, ICPAE at various doses showed a significant reduction in blood glucose and biochemical profiles in diabetic rats. CONCLUSION: Our findings confirm that the degree of maturity of carob characterized by a different phytochemical composition may be responsible for these actions. Therefore, these compounds may be used as a food supplement in hyperglycemia and diabetes treatments. © 2016 Society of Chemical Industry.

Effect of grape seed and skin supplement on milk yield and composition of dairy ewes.

In the present study, we investigated the effect of grape seed and skin supplement (GSSS), on lactating dairy ewes' production. Ten dairy pregnant ewes from northern Tunisia were allocated to two groups: control diet (C) and supplemented with 20 % (w/w) GSSS. The experiment lasted for 8 weeks and took place after 2 months of lambing. During the experiment, daily milk yield and milk composition were determined. Supplementation of the diet with GSSS increased milk production (P < 0.001), calcium (P < 0.01), free iron (P < 0.01) and urea content (P < 0.001) but had no effect on milk fat nor protein. From these data, it is concluded that the inclusion of GSSS in sheep diets increased significantly ewes' milk yield.

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.

Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia.

Hereditary spastic paraplegias (HSPs) form a heterogeneous group of neurological disorders. A whole-genome linkage mapping effort was made with three HSP-affected families from Spain, Portugal, and Tunisia and it allowed us to reduce the SPG26 locus interval from 34 to 9 Mb. Subsequently, a targeted capture was made to sequence the entire exome of affected individuals from these three families, as well as from two additional autosomal-recessive HSP-affected families of German and Brazilian origins. Five homozygous truncating (n = 3) and missense (n = 2) mutations were identified in B4GALNT1. After this finding, we analyzed the entire coding region of this gene in 65 additional cases, and three mutations were identified in two subjects. All mutated cases presented an early-onset spastic paraplegia, with frequent intellectual disability, cerebellar ataxia, and peripheral neuropathy as well as cortical atrophy and white matter hyperintensities on brain imaging. B4GALNT1 encodes ß-1,4-N-acetyl-galactosaminyl transferase 1 (B4GALNT1), involved in ganglioside biosynthesis. These findings confirm the increasing interest of lipid metabolism in HSPs. Interestingly, although the catabolism of gangliosides is implicated in a variety of neurological diseases, SPG26 is only the second human disease involving defects of their biosynthesis.

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.

Grape seed and skin extract protects kidney from doxorubicin-induced oxidative injury.

The study investigated the protective effect of grape seed and skin extract (GSSE) against doxorubicin-induced renal toxicity in healthy rats. Animals were treated with GSSE or not (control), for 8 days, administered with doxorubicin (20mg/kg) in the 4th day, and renal function as well as oxidative stress parameters were evaluated. Data showed that doxorubicin induced renal toxicity by affecting renal architecture and plasma creatinine. Doxorubicin also induced an oxidative stress characterized by an increase in malondialdehyde (MDA), calcium and H(2)O(2) and a decrease in catalase (CAT) and superoxide dismutase (SOD). Unexpectedly doxorubicin increased peroxidase (POD) and decreased carbonyl protein and plasma urea. Treatment with GSSE counteracted almost all adverse effects induced by doxorubicin. Data suggest that doxorubicin induced an oxidative stress into rat kidney and GSSE exerted antioxidant properties, which seem to be mediated by the modulation of intracellular calcium.

Gastroprotective effect of carob (Ceratonia siliqua L.) against ethanol-induced oxidative stress in rat.

BACKGROUND: We aimed in the present study, at investigating the gastroprotective effect of carob pods aqueous extract (CPAE) against ethanol-induced oxidative stress in rats as well as the mechanism implicated. METHODS: Adult male wistar rats were used and divided into six groups of ten each: control, EtOH (80% v/v, 4 g/kg b.w.), EtOH 80% + various doses of CPAE (500, 1000 and 2000 mg/kg, b.w.) and EtOH + Famotidine (10 mg/kg, p.o.) Animals were perorally (p.o.) pre-treated with CPAE during 15 days and intoxicated with a single oral administration of EtOH (4 g/kg b.w.) for two hours. RESULTS: The colorimetric analysis demonstrated that the CPAE exhibited an importance in vitro antioxidant activity against ABTS and DPPH radicals. We found that CPAE pretreatment in vivo, protected against EtOH-induced macroscopic and histological changes induced in stomach mucosa. Carob extract administration also protected against alcohol-induced volume gastric juice decrease. More importantly, We showed that CPAE counteracted EtOH-induced gastric lipoperoxidation, reversed the decrease of sulfhydryl groups (-SH) an hydrogen peroxide (H2O2) levels, and prevented the depletion of antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). CONCLUSIONS: These findings suggest that CPAE exerted a potential gastro-protective effect against EtOH-induced oxidative stress in rats, due in part, to its antioxidants properties.

Hepatoprotective effect of carob against acute ethanol-induced oxidative stress in rat.

The present study was undertaken to determine whether subacute treatment with aqueous extract of carob (Ceratonia siliqua L.) pods (AECPs) protects against ethanol (EtOH)-induced oxidative stress in rat liver. Animals were divided into four groups: control, carob, EtOH and EtOH + carob. Wistar rats were intraperitoneally pretreated with AECP (600 mg/kg body weight (bw)) during 7 days and intoxicated for 6 h by acute oral administration of EtOH (6 g/kg bw) 24 h after the last injection. We found that acute administration of EtOH leads to hepatotoxicity as monitored by the increase in the levels of hepatic marker aspartate aminotransferase and alanine aminotransferase as well as hepatic tissue injury. EtOH also increased the formation of malondialdehyde in the liver, indicating an increase in lipid peroxidation and depletion of antioxidant enzyme activities as superoxide dismutase, catalase and glutathione peroxidase. Subacute carob pretreatment prevented all the alterations induced by EtOH and returned their levels to near normal. Importantly, we showed that acute alcohol increased hepatic and plasmatic hydrogen peroxide and free iron levels. The carob pretreatment reversed EtOH effects to near control levels. These data suggest that carob could have a beneficial effect in inhibiting the oxidative damage induced by acute EtOH administration and that its mode of action may involve an opposite effect on plasma and tissue-free iron accumulation. Indeed, carob can be offered as a food additive to protect against EtOH-induced oxidative damage.

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.