Attenuating effects of selenium and zinc against hexavalent chromium-induced oxidative stress, hormonal instability, and placenta damage in preimplanted rats.

As a toxic metal, hexavalent chromium (CrVI) has effects on both the reproductive and endocrine systems. This study aimed to evaluate the protective effects of selenium (Se) and zinc (Zn) against the toxicity of chromium on the placenta in pregnant Wistar albino rats. Thirty pregnant Wistar rats were divided into control and four treated groups, receiving subcutaneously (s.c) on the 3rd day of pregnancy, K2Cr2O7 (10 mg/kg body weight (bw)) alone, or in association with Se (0.3 mg/kg bw), ZnCl2 (20 mg/kg bw), or both of them simultaneously. Plasma steroid hormones, placenta histoarchitecture, oxidative stress profile, and developmental parameters were investigated. These results showed that K2Cr2O7 exposure induced a significant increase in the levels of both plasma estradiol (E2) and placenta malondialdehyde (MDA), the number of fetal resorptions, and percent of post-implantation loss. On the other hand, K2Cr2O7 significantly reduced developmental parameters, maternal body and placenta weight, and plasma progesterone (P) and chorionic gonadotropin hormone (ß HCG) levels. However, K2Cr2O7 significantly decreased the placenta activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), and nonprotein sulfhydryl (NPSH). These changes have been reinforced by histopathological evaluation of the placenta. Se and/or ZnCl2 supplementation provoked a significant improvement in most indices. These results suggest that the co-treatment with Se or ZnCl2 strongly opposes the placenta cytotoxicity induced by K2Cr2O7 through its antioxidant action.

Melatonin Improves Endoplasmic Reticulum Stress-Mediated IRE1α Pathway in Zücker Diabetic Fatty Rat.

Obesity and diabetes are linked to an increased prevalence of kidney disease. Endoplasmic reticulum stress has recently gained growing importance in the pathogenesis of obesity and diabetes-related kidney disease. Melatonin, is an important anti-obesogenic natural bioactive compound. Previously, our research group showed that the renoprotective effect of melatonin administration was associated with restoring mitochondrial fission/fusion balance and function in a rat model of diabesity-induced kidney injury. This study was carried out to further investigate whether melatonin could suppress renal endoplasmic reticulum (ER) stress response and the downstream unfolded protein response activation under obese and diabetic conditions. Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally supplemented either with melatonin (10 mg/kg body weight (BW)/day) (M-ZDF and M-ZL) or vehicle (C-ZDF and C-ZL) for 17 weeks. Western blot analysis of ER stress-related markers and renal morphology were assessed. Compared to C-ZL rats, higher ER stress response associated with impaired renal morphology was observed in C-ZDF rats. Melatonin supplementation alleviated renal ER stress response in ZDF rats, by decreasing glucose-regulated protein 78 (GRP78), phosphoinositol-requiring enzyme1α (IRE1α), and ATF6 levels but had no effect on phospho-protein kinase RNA-like endoplasmic reticulum kinase (PERK) level. In addition, melatonin supplementation also restrained the ER stress-mediated apoptotic pathway, as indicated by decreased pro-apoptotic proteins phospho-c-jun amino terminal kinase (JNK), Bax, and cleaved caspase-3, as well as by upregulation of B cell lymphoma (Bcl)-2 protein. These improvements were associated with renal structural recovery. Taken together, our findings revealed that melatonin play a renoprotective role, at least in part, by suppressing ER stress and related pro-apoptotic IRE1α/JNK signaling pathway.

Cardiopreventive capacity of a novel (E)-N'-(1-(7-methoxy-2-oxo-2H-chromen-3-yl) ethylidene)-4-methylbenzenesulfonohydrazide against isoproterenol-induced myocardial infarction by moderating biochemical, oxidative stress, and histological parameters.

This study is carried out to assess the cardiopreventive effect of (E)-N'-(1-(7-methoxy-2-oxo-2H-chromen-3-yl) ethylidene)-4-methylbenzenesulfonohydrazide or SHC, a novel synthesized coumarin, against myocardial infarction induced by isoproterenol (ISO). The SHC compound was identified and characterized by spectral methods (infrared, 1 H NMR [nuclear magnetic resonance], 13 C NMR, Nuclear Overhauser Effect Spectroscopy, and high-resolution mass spectroscopy). Male Wistar rats were divided into four groups: Control, ISO (rats were injected subcutaneously by 85 mg/kg body weight [BW] of isoproterenol at Days 6 and 7 of the experience), ISO + SHC (150 µg/kg BW, orally for 7 days) and ISO + acenocoumarol (150 µg/kg BW, orally for 7 days). Results showed that ISO induced a remarkable alteration of electrocardiogram (ECG) pattern and increases of plasma cardiac troponin T, creatine kinase-MB, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, lactate dehydrogenase, aspartate transaminase, and malondialdehyde. In addition, ISO reduced the high-density lipoprotein-cholesterol content and the activities of superoxide dismutase and glutathione peroxidase, with the induction of myocardial necrosis. However, SHC administration revealed a significant decrease in cardiac dysfunction markers, restored normal ECG pattern, as well as improving lipids parameters. Moreover, SHC treatment remarkably alleviated the cardiac oxidative stress and the myocardial remodeling process. Overall, the SHC offers good protection from acute myocardial infarction through the antioxidant capacity.

Anti-embolic and anti-oxidative effects of a novel (E)-4-amino-N'-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl) ethylidene) benzohydrazide against isoproterenol and vitamin-K induced ischemic stroke.

This study aimed to evaluate the cerebroprotective potential of a novel synthetic coumarin, (E)-4-amino-N'-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl)ethylidene) benzohydrazide noted (HC) against a pharmaceutically induced ischemic stroke in experimental male Wistar rats. Animals were randomly allocated into four groups: control, Stroke, Stroke + Ace (acenocoumarol) and Stroke + HC-treated group for 7 days. Our results showed that stroke group evidenced atrial flutter, significant cardiac hypertrophy (+23%) and increase in plasma level of troponin-T, with disturbance in plasma ionic levels and rise in fibrinogen rate and oxidative damages in heart and brain. Moreover, the histological findings revealed myocardium necrosis, cardiac cavity thrombi and brain injury as compared to normal rats. However, HC-treatment significantly prevents the embolic process, improves cerebral damages and mitigates the oxidative stress markers in stroke rats. Overall, HC is endowed with a thrombolytic potential against MI and stroke in such severe conditions through an anti-vit K (AVK) mechanism.

Potential Predictive Role of Lipid Peroxidation Markers for Type 2 Diabetes in the Adult Tunisian Population.

OBJECTIVES: We evaluated the potential clinical relevance of malondialdehyde (MDA) and autoantibodies to copper oxidized low-density lipoprotein (CuOx-LDL) in type 2 diabetes occurrence. METHODS: This cross-sectional study enrolled 69 normoglycemic subjects, 18 prediabetic patients and 108 type 2 diabetes patients. MDA concentration was assessed spectrophotometrically. Plasma IgG, IgA and IgM levels to CuOx-LDL were determined by ELISA. RESULTS: Plasma MDA levels were considerably higher in obese, prediabetic and type 2 diabetes subjects compared to controls. In multiple linear regression analysis, both MDA and IgA to CuOx-LDL were significantly associated with glucose metabolism markers (p<0.05). Multiple logistic regression analyses showed that high plasma MDA and IgA to CuOx-LDL were independent risk factors for type 2 diabetes (OR 1.196, 95% CI: 1.058 to 1.353; p=0.004; OR 1.626, 95% CI: 1.066 to 2.481; p=0.024; respectively). Importantly, elevated IgA to CuOx-LDL predicted incident diabetes in patients with prediabetes (OR 2.321, 95% CI:1.063 to 5.066; p=0.035). From stratified analyses by body mass index (BMI), both MDA and IgA to CuOx-LDL remained independent predictors of type 2 diabetes occurrence in non-obese subjects (p<0.05). More interesting, elevated IgA to CuOx-LDL levels could be predictors of type 2 diabetes in obese prediabetic subjects (p=0.044). Conversely, neither IgG nor IgM to CuOx-LDL was associated with glucose metabolism markers, obesity or type 2 diabetes. CONCLUSIONS: Plasma MDA and IgA to CuOx-LDL were significantly associated with blood markers of glucose metabolism. High levels of MDA and IgA to CuOx-LDL could independently predict type 2 diabetes development in normoglycemia and prediabetic subjects.

In vitro and in vivo studies of Allium sativum extract against deltamethrin-induced oxidative stress in rats brain and kidney.

The present study investigated the in vitro and the in vivo antioxidant capacities of Allium sativum (garlic) extract against deltamethrin-induced oxidative damage in rat's brain and kidney. The in vitro result showed that highest extraction yield was achieved with methanol (20.08%). Among the tested extracts, the methanol extract exhibited the highest total phenolic, flavonoids contents and antioxidant activity. The in vivo results showed that deltamethrin treatment caused an increase of the acetylcholinesterase level (AChE) in brain and plasma, the brain and kidney conjugated dienes and lipid peroxidation (LPO) levels as compared to control group. The antioxidant enzymes results showed that deltamethrin treatment induced a significantly decrease (p < 0.01) in brain and kidney antioxidant enzymes as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) to control group. The co-administration of garlic extract reduced the toxic effects in brain and kidney tissues induced by deltamethrin.

Investigation of phytochemical contents, in vitro antioxidant and antibacterial behavior and in vivo anti-inflammatory potential of Ecballium elaterium methanol fruits extract

Abstract Ecballium elaterium species are mostly used as therapeutic agents and food ingredient. The current work was designed to investigate phytochemical contents, antioxidant, antibacterial, and anti-inflammatory properties of methanol fruits extract of Ecballium elaterium. Good antioxidant activity was observed with IC50 values of 156 ± 4 and 377 ± 6 μg/mL for DPPH and ABTS, respectively, and EC50 of 126 ± 4 µg/mL for FRAP assays, which is related with their richness in total phenolic, flavonoid and condensed tannins contents. The results of antibacterial activity showed the effectiveness of methanol extract against Bacillus cereus with value of inhibition zone diameter of 15 ± 0 mm and a MIC and MBC values of 6 ± 0 and 12 ± 0 mg/mL, respectively. The in vivo anti-inflammatory effects have been also studied by carrageenan induced rat paw edema assay and the results revealed that a dose of 75 mg/kg induced a significant inhibition of 66.4% at 2 h. FT-IR spectral data justified the presence of biological functional groups such as ─OH, C─H, C─O, C─C and C=O. These results highlighted the potential using of Ecballium elaterium fruits extract as natural antimicrobial, antioxidant and anti-inflammatory agents for food applications and for the pharmaceutical industry.

Deltamethrin induced oxidative stress in kidney and brain of rats: Protective effect of Artemisia campestris essential oil.

Artemisia campestris (Asteraceae) is widely used in traditional medicine in Southern Tunisia as a decoction for its antivenom, anti-inflammatory, antirheumatic, and antimicrobial activities. A. campestris essential oil (ACEO) was obtained by hydrodistillation from the aerial parts, since it has beneficial and therapeutic effects. Deltamethrin is a synthetic pyrethroid with broad spectrum activities against acaricides and insects and widely used for veterinary and agricultural purposes. Exposure to deltamethrin leads to nephrotoxic and neurotoxic side effects for human and many species including birds and fish. The present study was conducted to investigate the potential nephroprotective, neuroprotective and antioxidant effects of ACEO against sub-acute deltamethrin toxicity in male rats. Deltamethrin intoxicated rats revealed a significant increase in serum kidney and brain indicators as well as creatinin, urea and uric acid levels, and AChE activity as compared to control rats. In addition, kidney and brain lipid peroxidation and antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were altered significantly in deltamethrin treated rats. These biochemical disturbances were confirmed by histological and histomorphometric changes in brain and kidney tissues. However, ACEO normalized the altered serum levels of creatinin, urea, uric acid, and AChE. Moreover, ACEO reduced deltamethrin-induced lipid peroxidation and oxidative stress profile. Furtheremore, it reduced deltamethrin-induced histopathology and histomorphometric degeneration. It can be concluded that the protective effect of ACEO may be attributed to its antioxidant properties.

Chemical components, antioxidant potential and hepatoprotective effects of Artemisia campestris essential oil against deltamethrin-induced genotoxicity and oxidative damage in rats.

In the present study, we evaluated the antioxidant potential of Artemisia campestris essential oil (ACEO) and the possible protective effects against deltamethrin induced hepatic toxic effects. The ACEO showed radical scavenging activity with IC50 = 47.66 ± 2.51 µg/ml, ferric reducing antioxidant power (FRAP) potential (EC50 = 5.36 ± 0.77 µg/ml), superoxide scavenging activity (IC50 = 0.175 ± 0.007 µg/ml) and ˙OH scavenging activity (IC50 = 0.034 ± 0.007 µg/ml). The obtained results of phenolic profile demonstrated that phenolic compounds are the major contributor to the antioxidant activity of ACEO. GC-MS analysis revealed the presence of 61 components in which monoterpene hydrocarbons constitute the major fraction (38.85%). In in vivo study, deltamethrin exposure caused an increase of serum AST, ALT and ALP activities, hepatic malondialdehyde (MDA) (measured as TBARS) and conjugated dienes markers of lipid peroxidation (LPO), while antioxidant enzyme activities (SOD, CAT and GPx) decreased significantly. Furthermore, it induces DNA damage as indicated by DNA fragmentation accompanied with severe histological changes in the liver tissues. The treatment with vitamin E or ACEO significantly improved the hepatic toxicity induced by deltamethrin. It can be concluded that vitamin E and ACEO are able to improve the hepatic oxidative damage induced by deltamethrin. Therefore, ACEO is an important product in reducing the toxic effects of deltamethrin.

Liver injury following small intestinal ischemia reperfusion in rats is attenuated by Pistacia lentiscus oil: antioxidant and anti-inflammatory effects.

CONTEXT: Intestinal ischemia-reperfusion (IIR) not only leads to severe intestine damage but also induced subsequent destruction of remote organs. OBJECTIVE: We investigated the protective effect of Pistascia lentiscus L. (Anacardiaceae) oil on IIR. MATERIALS AND METHODS: Wistar rats were divided into three groups: sham, intestinal IR and P. lentiscus pretreatment (n = 18 each). In the pretreatment group, oil was administered 1 h before induction of warm ischemia. RESULTS: IIR led to severe liver damage manifested as a significant (p < .05) increase of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Pistacia lentiscus oil decreased the visible intestinal damage, as well as a significant decrease in serum AST and ALT levels. In addition, Pistacia lentiscus reduce liver injury, as evidenced by the decrease in liver tissue myeloperoxidase activity and lipoperoxidation (MDA) level. CONCLUSION: Pistascia lentiscus attenuates liver injury induced by IIR, attributable to the antioxidant and anti-inflammatory effect.

Protective effects of Zygophyllum album extract against deltamethrin-induced hyperglycemia and hepato-pancreatic disorders in rats.

The current study was designed to investigate the possible mechanism involved in hyperglycemia induced by chronic exposure to deltamethrin (DLM) in rat and to assess whether this damage is amenable to modulation by Zygophyllum album. DLM, a synthetic pyrethroid pesticide, was administrated at a dose of 4 mg/kg body mass, during 60 days. Compared with control, DLM showed a significant increase of blood glucose (p ≤ 0.01) and glycosylated hemoglobin levels (p ≤ 0.01) and a clear decrease (p ≤ 0.01) of insulin and total hemoglobin levels. In addition, hepatic glycogen content and the activity of hexokinase decreased (p ≤ 0.01), whereas the activities of glucose-6-phosphatase and glycogen phosphorylase were significantly increased (p ≤ 0.01). Moreover, pancreatic lipid peroxidation (TBARS level) was higher (p ≤ 0.01) and oxidative stress biomarkers (SOD, CAT, GPx, and GSH) were altered owing to DLM toxicity. However, Z. album, when combined with DLM, significantly ameliorated almost all the hepato-pancreatic disorders induced by DLM alone. Furthermore, Z. album supplement was found to be effective in preserving the normal histological appearance of hepatic and pancreatic tissue. In conclusion, this study suggested that, owing to its antioxidant effects, methanolic extract of Z. album (MEZAL) can potentially prevent the hyperglycemia observed in DLM-treated group.

Histopathological, oxidative damage, biochemical, and genotoxicity alterations in hepatic rats exposed to deltamethrin: modulatory effects of garlic (Allium sativum).

Deltamethrin is a pesticide widely used as a synthetic pyrethroid. The aim of this study was undertaken to investigate the effects of deltamethrin to induce oxidative stress and changes in biochemical parameters, hepatotoxicity and genotoxicity in female rats following a short-term (30 days) oral exposure and attenuation of these effects by Allium sativum extract. Indeed, Allium sativum is known to be a good antioxidant food resource which helps destroy free radical particles. Our results showed that deltamethrin treatment caused an increase in liver enzyme activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH); and hepatic lipid peroxidation (LPO) level. However, it induced a decrease in activities of hepatic catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) (p < 0.01). Allium sativum extract normalized significantly (p < 0.01) the mentioned parameters in deltamethrin-treated rats. For genotoxic evaluation, deltamethrin treatment showed a significant increase in frequencies of micronucleus in bone-marrow cells. Micronucleus formation is an indicator of chromosomal damage which has been increasingly used to detect the genotoxic potential of environmental pests. The present study showed that Allium sativum diminished the adverse effects induced by this synthetic pyrethroid insecticide.