Antiapoptotic effects of vitamins C and E against cypermethrin‐induced oxidative stress and spermatogonial germ cell apoptosis

Toxicological studies have demonstrated the relation between use of agrochemicals and fertility issues within males. Thus, the present study aimed to elucidate the propensity of cypermethrin (CYP) in bringing testicular germ cell apoptosis and effective attenuation by vitamins C and E in caprines. Reproductive toxicity of CYP was evaluated using histomorphological, cytological, and biochemical changes in the testicular germ cells in dose‐dependent (1, 5, 10 μg/mL) and time‐dependent (4, 6, 8 h) manner. Histological and ethidium bromide/acridine orange fluorescence staining exhibited that vitamins C and E (0.5 and 1.0 mM) successfully diminished the CYP‐induced testicular germ cells apoptosis. CYP exposure along with vitamins C and E supplementation also resulted in significantly increased ferric reducing antioxidant power activity along with the antioxidant enzymes, namely catalase, superoxide dismutase, and glutathione‐s‐transferase, and decreased lipid peroxidation in testicular germ cells. Thus, vitamins C and E ameliorated CYP‐induced testicular germ cell apoptosis, thereby preventing spermatogonial cells degeneration and male infertility.     

S‐allyl cysteine,an active ingredient of garlic,attenuates acute liver dysfunction induced by lipopolysaccharide/ d‐galactosamine in mouse: Underlying mechanisms

In the present study, beneficial effect of S‐allyl cysteine (SAC) was evaluated in the lipopolysaccharide/d ‐galactosamine (LPS/d ‐Gal) model of acute liver injury (ALI). To mimic ALI, LPS and d ‐Gal (50 μg/kg and 400 mg/kg, respectively) were intraperitoneally administered and animals received SAC per os (25 or 100 mg/kg/d) for 3 days till 1 hour before LPS/d ‐Gal injection. Pretreatment of LPS/d ‐Gal group with SAC‐lowered activities of alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase and partially reversed inappropriate alterations of hepatic oxidative stress‐ and inflammation‐related biomarkers including liver reactive oxygen species, malondialdehyde, and hepatic activity of the defensive enzyme superoxide dismutase, ferric reducing antioxidant power (FRAP), toll‐like receptor‐4 (TLR4), cyclooxygenase 2, NLR family pyrin domain containing 3 (NLRP3), caspase 1, nuclear factor κB (NF‐κB), interleukin 1β (IL‐1β), IL‐6, tumor necrosis factor‐α, and myeloperoxidase activity. Additionally, SAC was capable to ameliorate apoptotic biomarkers including caspase 3 and DNA fragmentation. In summary, SAC can protect liver against LPS/d ‐Gal by attenuation of neutrophil infiltration, oxidative stress, inflammation, apoptosis, and pyroptosis which is partly linked to its suppression of TLR4/NF‐κB/NLRP3 signaling.     

Protective effect of aminoguanidine against oxidative stress and bladder injury in cyclophosphamide‐induced hemorrhagic cystitis in rat

Cyclophosphamide (CP) is an antineoplastic agent that is used for the treatment of many neoplastic diseases. Hemorrhagic cystitis (HC) is a major dose limiting side effect of CP. Recent studies show that aminogaunidine, an inhibitor of inducible nitric oxide synthase is a potent antioxidant and prevents changes caused by oxidative stress such as depletion of antioxidant activity and tissue injury. The purpose of the study is to investigate the effect of aminoguanidine on parameters of oxidative stress, antioxidant enzymes and bladder injury caused by CP. Adult male rats were randomly divided into four groups. Control rats were administered saline; the AG control group received 200 mg/kg body wt of aminoguanidine; The CP group received a single injection of CP at the dose of 150 mg/kg body wt intraperitoneally. The CP + AG group received aminoguanidine (200 mg/kg body wt) intraperitoneally 1 h before the administration of CP. The rats were sacrificed 16 h after CP/saline administration. The bladder was used for light microscopic studies and biochemical studies. The markers of oxidative damage including protein carbonyl content, protein thiol, malondialdehyde and conjugated dienes were assayed in the homogenates along with the activities of the antioxidant enzymes, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase and glutathione S transferase. In the bladders of CP treated rats edema of lamina propria with epithelial and sub‐epithelial hemorrhage was seen. All the parameters of oxidative stress that were studied were significantly elevated in the bladders of CP treated rats. The activities of the antioxidant enzymes were significantly lowered in the bladders of CP treated rats. Aminoguanidine pretreatment prevented CP‐induced oxidative stress, decrease in the activities of anti‐oxidant enzymes and reduced bladder damage. The results of the present study suggest the antioxidant role for aminoguanidine in CP‐induced bladder damage. Copyright © 2008 John Wiley & Sons, Ltd.     

Protective effects of antioxidant combination against D‐galactosamine‐induced kidney injury in rats

The protective effects of an antioxidant combination in kidney injury induced by the injection of D‐galactosamine (D‐GaIN) were examined in the present study. Sprague Dawley female rats were used and divided into four groups as follows: (1) animals injected physiological saline solution, intraperitoneally, (2) animals treated with the combination of ascorbic acid (100 mg kg^?1 day^?1), β‐carotene (15 mg kg^?1 day^?1), α‐tocopherol (100 mg kg^?1 day^?1), and sodium selenate (0.2 mg kg^?1 day^?1) for three days orally, (3) rats injected D‐GaIN (500 mg kg^?1) intraperitoneally as a single dose, and (4) animals treated with the antioxidant combination for three days, then injected D‐GaIN. The tissue and blood samples of animals were collected for morphological and biochemical evaluations. Histopathological injury in kidney tissues was observed together with a significant increase in tissue lipid peroxidation (LPO) level, myeloperoxidase (MPO), lactate dehydrogenase, catalase and superoxide dismutase (SOD) activities, and serum creatinine and urea levels, and a significant decrease in glutathione level and glutathione peroxidase activity in D‐GaIN injected rats. However, a decrease in the degenerative changes was detected in the kidney tissue of D‐GaIN + antioxidant group, and biochemical results showed reversed effects. In conclusion, it seems reasonable to conclude that the treatment of the antioxidant combination has a protective effect on D‐GaIN‐induced kidney injury of rats. Copyright © 2010 John Wiley & Sons, Ltd.     

Triphlorethol-A from Ecklonia cava protects V79-4 lung fibroblast against hydrogen peroxide induced cell damage

In the present study, triphlorethol-A, a phlorotannin, was isolated from Ecklonia cava and its antioxidant properties were investigated. Triphlorethol-A was found to scavenge intracellular reactive oxygen species (ROS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, and thus prevented lipid peroxidation. The radical scavenging activity of triphlorethol-A protected the Chinese hamster lung fibroblast (V79-4) cells exposed to hydrogen peroxide (H₂O₂) against cell death, via the activation of ERK protein. Furthermore, triphlorethol-A reduced the apoptotic cells formation induced by H₂O₂. Triphlorethol-A increased the activities of cellular antioxidant enzymes like, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Hence, from the present study, it is suggestive that triphlorethol-A protects V79-4 cells against H₂O₂ damage by enhancing the cellular antioxidative activity.     

Loperamide‐induced cardiotoxicity in rats: Evidence from cardiac and oxidative stress biomarkers

At therapeutic dose, loperamide is a safe over‐the‐counter antidiarrheal drug but could induce cardiotoxic effect at a supratherapeutic dose. In this study, we use cardiac and oxidative biomarkers to evaluate loperamide‐induced cardiotoxicity in rats. Rats were orally gavaged with 1.5, 3, or 6 mg/kg body weight (BW) of loperamide hydrochloride for 7 days. The results after 7 days administration of loperamide, revealed dose‐dependent increase (P < 0.05) in aspartate aminotransferase, lactate dehydrogenase, creatine kinase‐MB, and serum concentration of cardiac troponin I, total homocysteine, and nitric oxide. A 50% decrease in antioxidant enzymes activity was observed at 6 mg/kg BW. Furthermore, malondialdehyde and fragmented DNA also increased significantly in the heart of the treatment groups. Loperamide provoked cardiotoxicity through oxidative stress, lipid peroxidation, and DNA fragmentation in rats. This study has provided a possible biochemical explanation for the reported cardiotoxicity induced by loperamide overdose.     

Rutin ameliorates copper sulfate‐induced brain damage via antioxidative and anti‐inflammatory activities in rats

Excessive exposure to Copper (Cu) may result in Cu toxicity and adversely affect health outcomes. We investigated the protective role of rutin on Cu‐induced brain damage. Experimental rats were treated as follows: group I: control; group II: Cu‐sulfate: 200 mg/kg; group III: Cu‐sulfate, and rutin 100 mg/kg; and group IV: rutin 100 mg/kg, for 7 weeks. Cu only treatment significantly decreased body weight gain, while rutin cotreatment reversed this decrease. Cu treatment increased malondialdehyde, nitric oxide level, and myeloperoxidase activity and decreased superoxide dismutase and catalase activities in rat brain. Immunohistochemistry showed that COX‐2, iNOS, and Bcl‐2 proteins were strongly expressed, while Bax was mildly expressed in the brain of Cu‐treated rats. Furthermore, brain histology revealed degenerated neurons, and perforated laminae of cerebral cortex in the Cu‐only treated rats. Interestingly, coadministration of Cu and rutin reduced the observed histological alteration, improved inflammatory and antioxidant biomarkers, thereby protecting against Cu‐induced brain damage via antioxidative and anti‐inflammatory mechanisms.     

Hepatoprotective effect of bis(4‐methylbenzoyl) diselenide against CCl4‐induced oxidative damage in mice

From a pharmacological point of view, organoseleniums are compounds with important and interesting antioxidant and biological activities. The aim of this study was to evaluate the hepatoprotective effect of bis(4‐methylbenzoyl) diselenide (BMD) against carbon tetrachloride (CCl₄)–induced oxidative damage in mice. The animals received BMD (25 mg/kg p.o., for 3 days), and after 1 day, CCl₄ (1 mg/kg body weight) was administered by intraperitoneal route. One day after the CCl₄ exposure, the animals were euthanized for biochemical and histological analysis. Treatment with BMD (25 mg/kg p.o.) protected against aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma‐glutamyl transferase and lactate dehydrogenase activity increases induced by CCl₄ plasma exposure. Treatment with BMD (25 mg/kg) protected against increases in thiobarbituric reactive species and decreasing non‐protein thiols and ascorbic acid levels in liver of mice. Catalase and superoxide dismutase activity inhibition in the liver caused by CCl₄ were protected by treatment with BMD (25 mg/kg). Glutathione S‐transferase activity was inhibited by CCl₄ and remained unaltered even after treatment with BMD. Sections of liver from CCl₄‐exposed mice presented an intense infiltration of inflammatory cells and loss of the cellular architecture. BMD (25 mg/kg) attenuated CCl₄‐induced hepatic histological alterations. The results demonstrated the hepatoprotective effects of BMD in the mouse liver, possibly by modulating the antioxidant status. Copyright © 2012 John Wiley & Sons, Ltd.     

Walker-256 tumor growth causes oxidative stress in rat brain

The elevated rate of oxygen consumption and high amount of polyunsaturated fatty acids make the central nervous system vulnerable to oxidative stress. The effect of Walker-256 tumor growth on oxi-reduction indexes in the hypothalamus (HT), cortex (CT), hippocampus (HC) and cerebellum (CB) of male Wistar rats was investigated. The presence of the tumor caused an increase in thiobarbituric acid reactant substances (TBARs) in the HT, CB and HC. Due to tumor growth, the activity of glucose-6-phosphate dehydrogenase increased in the HT and CB, whereas citrate synthase activity was reduced in the HT, CT and CB. Therefore, the potential for generation of reducing power is increased in the cytosol and decreased in the mitochondria of various brain regions of Walker-256 tumor-bearing rats. These changes occurred concomitantly with an unbalance in the brain enzymatic antioxidant system. The tumor decreased the activities of catalase in the HT and CB and of glutathione peroxidase in the HT, CB and HC, and raised the CuZn-superoxide dismutase activity in the HT, CB and HC. These combined findings indicate that Walker-256 tumor growth causes oxidative stress in the brain.     

Hypoxia‐induced apoptosis of astrocytes is mediated by reduction of Dicer and activation of caspase‐1

Hypoxia is a condition in which the whole body or a region of the body is deprived of oxygen supply. The brain is very sensitive to the lack of oxygen and cerebral hypoxia can rapidly cause severe brain damage. Astrocytes are essential for the survival and function of neurons. Therefore, protecting astrocytes against cell death is one of the main therapeutic strategies for treating hypoxia. Hence, the mechanism of hypoxia‐induced astrocytic cell death should be fully elucidated. In this study, astrocytes were exposed to hypoxic conditions using a hypoxia work station or the hypoxia mimetic agent cobalt chloride (CoCl₂). Both the hypoxic gas mixture (1% O₂) and chemical hypoxia‐induced apoptotic cell death in T98G glioblastoma cells and mouse primary astrocytes. Reactive oxygen species were generated in response to the hypoxia‐mediated activation of caspase‐1. Active caspase‐1 induced the classical caspase‐dependent apoptosis of astrocytes. In addition, the microRNA processing enzyme Dicer was cleaved by caspase‐3 during hypoxia. Knockdown of Dicer using antisense oligonucleotides induced apoptosis of T98G cells. Taken together, these results suggest that astrocytic cell death during hypoxia is mediated by the reactive oxygen species/caspase‐1/classical caspase‐dependent apoptotic pathway. In addition, the decrease in Dicer levels by active caspase‐3 amplifies this apoptotic pathway via a positive feedback loop. These findings may provide a new target for therapeutic interventions in cerebral hypoxia.     

A single dose of S‐ketamine induces long‐term antidepressant effects and decreases oxidative stress in adulthood rats following maternal deprivation

Ketamine, an antagonist of N‐methyl‐d ‐aspartate receptors, has produced rapid antidepressant effects in patients with depression, as well as in animal models. However, the extent and duration of the antidepressant effect over longer periods of time has not been considered. This study evaluated the effects of single dose of ketamine on behavior and oxidative stress, which is related to depression, in the brains of adult rats subjected to maternal deprivation. Deprived and nondeprived Wistar rats were divided into four groups nondeprived + saline; nondeprived + S‐ketamine (15 mg/kg); deprived + saline; deprived + S‐ketamine (15 mg/kg). A single dose of ketamine or saline was administrated during the adult phase, and 14 days later depressive‐like behavior was assessed. In addition, lipid damage, protein damage, and antioxidant enzyme activities were evaluated in the rat brain. Maternal deprivation induces a depressive‐like behavior, as verified by an increase in immobility and anhedonic behavior. However, a single dose of ketamine was able to reverse these alterations, showing long‐term antidepressant effects. The brains of maternally deprived rats had an increase in protein oxidative damage and lipid peroxidation, but administration of a single dose of ketamine reversed this damage. The activities of antioxidant enzymes superoxide dismutase and catalase were reduced in the deprived rat brains. However, ketamine was also able to reverse these changes. In conclusion, these findings indicate that a single dose of ketamine is able to induce long‐term antidepressant effects and protect against neural damage caused by oxidative stress in adulthood rats following maternal deprivation. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1268–1281, 2015     

The protective effect of melatonin against cypermethrin-induced oxidative stress damage in Spodoptera litura (Lepidoptera: Noctuidae)

Antioxidant enzymes form the first-line defense against free radicals damage in organisms. Their regulation depends mainly on the oxidant and antioxidant status of the cell, given that oxidants are their principal modulators. Therefore, the aim of the present study was to investigate the effect of melatonin on synthetic pyrethroid insecticide-induced antioxidative enzymes activity in Spodoptera litura larvae. In addition, activities of enzymatic antioxidants viz. superoxide dismutase (SOD), glutathione S-transferase (GST), catalase (CAT), glutathione reductase (GR), α, β-esterase, and acetylcholine esterase (AChE) were assessed. There was no significant change in GST levels in the melatonin-treated groups. Melatonin modulates cypermethrin-induced changes in the activities of esterase and AChE, whereas SOD, CAT, and GR activity was significantly increased in melatonin-treated samples when compared to control. In conclusion, the results of the current study revealed that SP toxicity activated oxidant systems in all antioxidant systems in some tissues of insects. Melatonin administration led to a marked increase in antioxidant activity and inhibited GST and AChE in most of the tissues studied.     

Alterations in tissue glutathione antioxidant system in streptozotocin-induced diabetic rats

Changes in tissue glutathione antioxidant system in streptozotocin-induced diabetic rats for a period of 15 weeks were examined. Total glutathione level was significantly increased in kidney tissue, but were slightly decreased and increased in liver and heart tissues, respectively. The small changes in total glutathione level in the liver and heart, though not statistically significant, were associated with reciprocal alterations in the activity Of -glutamylcysteine synthetase (GCS). While the GCS activity was not changed in kidney tissue, the activity of -glutathione peroxidase was significantly increased in kidney tissue. Insulin treatment could completely or partly normalize almost all of these changes induced by diabetes. However, the decrease in hepatic glutathione S-transferases activity in diabetic rats was not reversed by the insulin treatment. The ensemble of results suggests that the diabetes-induced alterations in tissue glutathione antioxidant system may possibly reflect an inter-organ antioxidant response to a generalized increase in tissue oxidative stress associated with diabetes.Abbreviations AGES advanced glycosylation end-products - EDTA ethylenediamine tetraacetic acid - GCS -glutamylcysteine synthetase - GlyHb glycated hemoglobin - GPX Se-glutathione peroxidase - GRD glutathione reductase - GSH reduced glutathione - GSSG oxidized glutathione - GST glutathione S-transferases - SSA sulfosalicylic acid - STZ streptozotocin     

Vitamin C and E combination modulates oxidative stress induced by X‐ray in blood of smoker and nonsmoker radiology technicians

X‐ray radiation is detrimental to human cells and may lead to development of life‐threatening diseases. Cigarette smoke contains about 500 chemicals that include organic and oxidant compounds whereas vitamin C and E (VCE) have scavenger effects on the compounds. We investigated effects of VCE administration on X‐ray‐induced oxidative toxicity in blood of smoker and nonsmoker X‐ray technicians. Twenty technicians and 30 healthy age‐matched subjects control were used in the study. Ten of the X‐ray technicians and 15 of the control were smokers. Blood samples were taken from the control. Oral vitamin C (500 mg) and vitamin E (150 mg) were daily supplemented to the smoker and nonsmoker X‐ray technicians for 5 weeks. Blood samples were taken from the X‐ray technicians after and before 5 weeks. Plasma and erythrocytes lipid peroxidation (LP), reduced glutathione (GSH) levels, erythrocytes glutathione peroxidase (GSH‐Px), and plasma antioxidant vitamin concentrations were investigated in control and X‐ray technicians with smoker and nonsmoker. Plasma and erythrocytes LP levels were higher in the total X‐ray group and smoker X‐ray group than in control and nonsmoker X‐ray group, respectively although the LP level was decreased by the VCE treatment. The plasma vitamin C, vitamin A, vitamin E, and β‐carotene concentrations were lower in the X‐ray group than in control although their concentrations were increased by the treatment. The erythrocytes GSH level and GSH‐Px activity were found to be higher in the treatment group than in the X‐ray group. Plasma GSH level was not found to be different in all group. Reactive oxygen species may play role in the mechanism that has been proposed to explain the biological side effect of X‐ray radiation and smoke. VCE prevents the smoke and X‐ray‐induced oxidative stress to strengthen antioxidant vitamin concentrations in the blood of the technicians. Copyright © 2009 John Wiley & Sons, Ltd.     

Rosmarinus officinalis essential oil modulates renal toxicity and oxidative stress induced by potassium dichromate in rats

BACKGROUNDChromium hexavalent (CrVI) is known as a toxic contaminant that induced oxidative stress and nephrotoxicity in humans and animals. Rosmarinus officinalis is a perennial herb rich in biologically active constituents that have powerful antioxidant properties. So, the current work evaluated the effectiveness of Rosmarinus officinalis essential oil (REO) against alterations induced by potassium dichromate in the kidney of male rats.METHODSGC-MS analysis, in vitro total phenol contents, and DPPH scavenging activity of REO were estimated. Thirty-five Wistar male rats were categorized into 5 groups. The first group was the control, the second one was orally administered rosemary essential oil (REO; 0.5 mL/kg BW), the third group was injected intraperitoneally with hexavalent chromium (CrVI; 2 mg/kg BW) for 14 days, the fourth group used as the protective group (REO was administrated 30 min before i.p. injection of CrVI) and the fifth group applied as the therapeutic group (rats injected with CrVI 30 min followed by oral administration of REO), respectively.RESULTSTwenty-nine components were detected with high total phenolic contents and high DPPH scavenging activity. Results revealed that CrVI- intoxicated rats showed a valuable increase in oxidative stress profile (TBARS and H₂O₂) and a notable decline in glutathione (GSH), total protein content, and enzymatic antioxidants (SOD, CAT, GPx, and GST). Furthermore, serum kidney functions biomarkers (urea, creatinine, and uric acid) were increased significantly. Also, the administration of CrVI showed histological and immunohistochemical (PCNA-ir) changes in rat kidney tissue. Otherwise, administration of REO pre or post-treatment with CrVI significantly restored most of the biochemical parameters in addition to improvement in kidney tissue architecture. Moreover, individual intake with REO exhibited an amendment in oxidative stress markers.CONCLUSIONConclusively, REO had a potential antioxidant capacity in ameliorating K₂Cr₂O₇-induced nephrotoxicity, especially in the protection group.     

The Relationship Between Yield and the Antioxidant Defense System in Tomatoes Grown Under Heat Stress

Four putative heat-tolerant tomato (Lycopersicum esculentum) cultivars (Tamasabro, Heat Wave, LHT-24, and Solar Set) and one putative heat-sensitive tomato culti-var (Floradade) were grown in the field under non-stress (average daily temperature of 26°C) and heat-stress (average daily temperature of 34°C) conditions. At anthesis, approximately five weeks after being transplanted to the field, leaf samples were collected for antioxidant analyses. Yield was determined by harvesting ripe fruit seven weeks after the collection of leaf samples. Heat stress resulted in a 79.1% decrease in yield for the heat-sensitive Floradade, while the fruit yield in the heat-tolerant cultivars Heat Wave, LHT-24, Solar Set, and Tamasabro was reduced 51.5%, 22.1%, 43.8%, and 34.8% respectively. When grown under heat stress, antioxidant activities were also greater in the heat-tolerant cultivars. Superoxide dismutase (SOD) activity increased up to 9-fold in the heat-tolerant cultivars but decreased 83.1% in the heat-sensitive Floradade. Catalase, peroxidase, and ascorbate peroxidase activity increased significantly in all cultivars. Only Heat Wave showed a significant increase in glutathione reductase in response to heat stress but all heat-tolerant cultivars exhibited significantly lower oxidized ascorbate/reduced ascorbate ratios, greater reduced glutathione/oxidized glutathione ratios, and greater a-tocopherol concentrations compared to the heat-sensitive cultivar Floridade. These data indicate that the more heat-tolerant cultivars had an enhanced capacity for scavenging active oxygen species and a more active ascorbate-glutathione cycle and suggest a strong correlation between the ability to up-regulate the antioxidant defense system and the ability of tomatoes to produce greater yields when grown under heat stress.     

Co‐occurring increases of calcium and organellar reactive oxygen species determine differential activation of antioxidant and defense enzymes in Ulva compressa (Chlorophyta) exposed to copper excess

In order to analyse copper‐induced calcium release and (reactive oxygen species) ROS accumulation and their role in antioxidant and defense enzymes activation, the marine alga Ulva compressa was exposed to 10 µM copper for 7 d. The level of calcium, extracellular hydrogen peroxide (eHP), intracellular hydrogen peroxide (iHP) and superoxide anions (SA) as well as the activities of ascorbate peroxidase (AP), glutathione reductase (GR), glutathione‐S‐transferase (GST), phenylalanine ammonia lyase (PAL) and lipoxygenase (LOX) were determined. Calcium release showed a triphasic pattern with peaks at 2, 3 and 12 h. The second peak was coincident with increases in eHP and iHP and the third peak with the second increase of iHP. A delayed wave of SA occurred after day 3 and was not accompanied by calcium release. The accumulation of iHP and SA was mainly inhibited by organellar electron transport chains inhibitors (OETCI), whereas calcium release was inhibited by ryanodine. AP activation ceased almost completely after the use of OETCI. On the other hand, GR and GST activities were partially inhibited, whereas defense enzymes were not inhibited. In contrast, PAL and LOX were inhibited by ryanodine, whereas AP was not inhibited. Thus, copper stress induces calcium release and organellar ROS accumulation that determine the differential activation of antioxidant and defense enzymes.     

High‐fat diet induced alteration in lipid enzymes and inflammation in cardiac and brain tissues: Assessment of the effects of Atorvastatin‐loaded nanoparticles

Treatment with Lipitor is associated with several adverse impacts. Here we investigated the effects of low Lipitor nanoparticles (atorvastatin calcium nanopartilcle [AC‐NP]), with size less than 100 , on enzymes of lipid metabolism and inflammation in cardiac, hepatic, and brain tissues of hypercholestremic adult male rats. Adult male rats were divided into five experimental groups. In group 1, the intact control (normal pellet diet), animals were fed a normal control diet; the other four groups were fed a high‐fat diet (HFD) for 6 weeks. After 6 weeks, groups from 2 to 5 were assigned as a positive control (HFD), HFD + Lipitor, HFD + AC‐NP‐R1, or HFD + AC‐NP‐R2. Different treatments were administrated orally for two regimen periods (R1 daily and R2 once every 3 days). The treatment was conducted for two consecutive weeks. The HFD group faced a significant elevation in 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA), associated with a significant reduction in low‐density lipoprotein receptor (LDL‐R) along with cholesterol 7 α‐hydroxylase enzyme in hepatic tissues, compared with the control group. Also, the HFD group induced hepatic, cardiac, and brain inflammation, evidenced by increased hepatic oxidative stress markers and cardiac homocysteine, together with elevated proinflammatory cytokines interleukin‐1β (IL‐1β) and IL‐6 levels in brain tissue, compared with the control group. Different AC‐NP treatments significantly augmented both mRNA LDL‐R and mRNA 7α‐hydroxylase expression in hepatic tissues, associated with significant depletion in mRNA HMG‐CoA expression, compared with HFD + Lipitor. The inflammation symptoms were ameliorated by the AC‐NP treatments, compared to HFD + Lipitor. Lipitor encapsulation in NP formulation results in increased efficiency and reduced dose‐related adverse effects known to be associated with the Lipitor chronic administration.