Oxidative Stress In Mice Research Articles

Small molecule inhibition of cyclic GMP-AMP synthase ameliorates sepsis-induced cardiac dysfunction in mice

AimsCardiac dysfunction is the main cause of multi-organ failure following sepsis within critical care units. The present study aimed to investigate the effects of the small molecule inhibition of cyclic GMP-AMP synthase (cGAS), RU.521, on cardiac function in mice with sepsis. Materials and methodsSepsis was induced in mice via intraperitoneal lipopolysaccharide (LPS) injection (10 mg/kg, i.p.). Mice subsequently received 5 mg/kg RU.521 within 10 min form LPS injection. The cardiac function, inflammatory factor and oxidative stress of mice were examined for 24 h following LPS injection. Key findingsRU.521 was indicated to significantly increase the cardiac function of mice with sepsis. In addition, the inflammatory responses, oxidative stress and apoptosis in hearts of sepsis mice were markedly mitigated by RU.521. Moreover, inhibition of Sirt3 inhibited the protective effects of RU.521 on mice with sepsis. SignificanceThe current study indicated that RU.521 alleviated the inflammatory response and alleviated the damage induced by oxidative stress, leading to cardiac protection via increased Sirt3 expression in the hearts of mice with sepsis.

A novel salvianolic acid A analog with resveratrol structure and its antioxidant activities in vitro and in vivo.

E-DRS is a novel salvianolic acid A (SAA) analog, which was synthesized from resveratrol (RES) and methyldopate. Its structure is similar to that of SAA, but the 3',4'-dihydroxy-trans-stilbene group and the ester structure in SAA were replaced by the RES structure and an amine group, respectively. E-DRS scavenged free oxygen radicals effectively, including superoxide anion (ascorbic acid > E-DRS > SAA ≥ rutin > RES) and DPPH radical (rutin > E-DRS ≥ ascorbic acid > SAA > RES), and exhibited powerful total antioxidant capacity (ascorbic acid > E-DRS > SAA ≥ rutin > RES) in vitro. Furthermore, oral administration of E-DRS dose-dependently and significantly decreased CCl4 -induced oxidative stress in mice as indicated by the decreased content of hepatic malondialdehyde (MDA). In addition, oral administration of E-DRS also increased the content of nonenzymatic antioxidant glutathione (GSH) and the activity of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) in the liver of mice. All these results demonstrated that E-DRS had good antioxidant activities both in vitro and in vivo, and could be a potential antioxidant agent after further optimization and evaluation.

ANO1 relieves pressure overload-induced myocardial fibrosis in mice by inhibiting TGF-β/Smad3 signaling pathway.

The aim of this study was to measure the expression of anoctamin 1 (ANO1) in myocardial tissues of mice with pressure overload-induced myocardial fibrosis, and to further investigate the effect of ANO1 on myocardial fibrosis in mice and its mechanism. A total of 40 male C57/B6 mice aged 6-8 weeks old were divided into 2 groups using a random number table, namely sham operation group (Sham group, n=20) and thoracic aortic constriction group (TAC group, n=20). Meanwhile, 20 ANO1 transgenic (TG) mice aged 6-8 weeks old were enrolled for TAC as TAC + ANO1 TG group. At 8 weeks after TAC, ejection fraction (EF%) and fraction shortening (FS%) in each group of mice were detected via echocardiography. Western blotting and immunofluorescence staining assays were conducted to measure the protein expression of ANO1 in myocardial tissues of mice in each group. The pathological changes in myocardial tissues of mice were evaluated through hematoxylin-eosin (H&E) staining. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assay was performed to measure the messenger ribonucleic acid (mRNA) expression levels of hypertrophy markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in myocardial tissues of mice in each group. The deposition of collagen fibers in heart tissues was determined by Masson staining assay. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining assay was carried out to detect the apoptosis of myocardial cells and fibroblasts in heart tissues. Additionally, the protein expressions of oxidative stress markers superoxide dismutase 1 (SOD1) and 4-hydroxynonenal (4-HNE) in myocardial tissues were detected as well. Finally, Western blotting was employed to detect the effect of ANO1 overexpression on the expression of transforming growth factor-β (TGF-β)/Smad3 signaling pathway-related proteins in myocardial tissues of mice. At 8 weeks after TAC, ANO1 expression was overtly reduced in myocardial tissues of mice (p<0.05). Echocardiographic results showed that ANO1 overexpression significantly alleviated TAC-induced cardiac function deterioration in mice (p<0.05). The mRNA expression levels of ANP and BNP in myocardial tissues of TAC + ANO1 TG group were evidently lower than those in TAC group (p<0.05). Meanwhile, myocardial interstitial collagen deposition was significantly ameliorated in TAC + ANO1 TG group compared with TAC group (p<0.05). ANO1 overexpression notably mitigated the apoptosis of myocardial cells and oxidative stress in mice with cardiac pressure overload (p<0.05). Western blotting results further indicated that after overexpression of ANO1, the protein levels of TGF-β and phosphorylated Smad3 (p-Smad3) were significantly inhibited in mice undergoing TAC (p<0.05). In the case of cardiac pressure overload in mice, ANO1 is lowly expressed in myocardial tissues. Meanwhile, its overexpression is able to attenuate pressure overload-induced myocardial fibrosis in mice by repressing the TGF-β/smad3 signaling pathway. All our findings indicate that ANO1 can serve as a potential gene target for the treatment of myocardial fibrosis in the future.

Antioxidant potential of Carica papaya Linn (Caricaceae) leaf extract in mice with cyclophosphamide induced oxidative stress

AIMS: This study aimed to investigate the effects of crude extract of Carica papaya leaves on oxidative stress in mice induced by cyclophosphamide, as well as phytochemical profile characterization of this extract.METHODS: The male Swiss mice received 15 days of treatment with the extract (500 mg kg-1, via gavage) and intraperitoneal injection of cyclophosphamide (75 mg kg-1) or saline (0.9%) on the 15th day. After 24 h the last treatment, the animals were anesthetized for blood withdrawal, sacrificed and removal of the organs for analyses (liver, kidney and heart). In the biochemical tests were determined: hematological parameters in blood, aminotransferases, alkaline phosphatase, glucose and total cholesterol dosages in plasma, enzymatic and non-enzymatic antioxidants and lipid damage marker were evaluated in different tissues, besides genotoxic and histopathological analyzes.RESULTS: In the extract of Carica papaya leaves, the flavonoids quercetin-3β-D-glucoside and rutin were identified, besides present positive results for alkaloids, saponins and tannins. This extract increased the activity of glutathione-S-transferase and catalase enzymes in the liver and reduced the levels of reduced glutathione in the kidneys and hematocrit levels, red cell count, and hemoglobin. It promoted the decrease of the reactive species of thiobarbituric acid (TBARS) in the kidneys and the activity of enzyme aspartate aminotransferase in the plasma and was antimutagenic in the micronucleus test.CONCLUSIONS: The study showed that extract of Carica papaya was beneficial against oxidative events and prevented DNA damage. The extract also showed hepatotoxicity, therefore prolonged infusion of papaya leaves is not advisable.

Antiamnesic effect of aqueous lyophilisate of Drymaria cordata on scopolamine-induced amnesia and oxidative stress in mice

Antiamnesic effect of aqueous lyophilisate of Drymaria cordata on scopolamine-induced amnesia and oxidative stress in mice

Lactobacillus fermentum JX306 Restrain D-galactose-induced Oxidative Stress of Mice through its Antioxidant Activity.

Oxidative stress-induced series of related degenerative diseases have received widespread attention. To screen new lactic acid bacteria (LAB) strains to resist oxidative stress, traditional Chinese fermented vegetables were used as a resource library to screen of LAB. The Lactobacillus fermentum JX306 strain, which showed high scavenging activity of DPPH free radical and hydrogen radical, and a strong lipid peroxidation inhibition rate in vitro was selected. L. fermentum JX306 was also examined for its antioxidant capacity in D-galactose-induced aging mice. The results showed that L. fermentum JX306 could significantly decrease malondialdehyde (MDA) levels and improve the activity of glutathione peroxidase (GSH-Px), and total antioxygenic capacity (TOC) in the serum, kidney, and liver. Meanwhile, the strain could remarkably upregulate the transcriptional level of the antioxidant-related enzyme genes, such as peroxiredoxin1 (Prdx1), glutathione reductase (Gsr), glutathione peroxidase (Gpx1), and thioredoxin reductase (TR3) encoding genes in the liver. Besides, histopathological observation proves that this probiotic strain could effectively inhibit oxidative damage to the liver and kidney in aging mice. Therefore, this unique antioxidant strain may have a high application value in the functional food industry and medicine industry.

Antioxidant activities of aqueous and ethyl acetate fractions of Daucus carota L. seed against triton X-100 induced oxidative stress in mice

Daucus carota seed is medicinally useful in the management of disease such as diabetes mellitus, which is associated with oxidative stress. This study investigated the phytochemical constituents, in vitro and in vivo antioxidant activities of aqueous fraction (AQF) and ethyl acetate fraction (EAF) of D. carota seed in triton X-100 induced oxidative stress. The fractions were obtained by partitioning aqueous extract of the seed in ethyl acetate. Oxidative stress was induced by intraperitoneal injection of triton X-100, after oral administration of the fractions in mice. The results revealed the presence of alkaloids, tannins and phenolics in AQF and EAF. AQF and EAF demonstrated significant in vitro antioxidant activities comparable to butylated hydroxytolune (BHT) with IC50 values of 0.30, 0.38 and 0.92 mg/ml respectively for DPPH scavenging activities. Induction of oxidative stress by triton X-100 caused increased malondialdehyde concentration in plasma and liver of experimental mice, which was significantly decreased (p<0.05) in the plasma of mice pre-administered with AQF and EAF. No significant change (p>0.05) was observed in the nitric oxide level in mice treated with AQF and EAF compared with triton X-100 control. The fractions caused a significant decrease (p<0.05) in plasma activities of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) but no significant alteration (p>0.05) in plasma glutathione peroxidase (GPx) and glutathione-S-transferase (GST). The pre-administration also resulted in decreased SOD and increased GPx (p<0.05) in the liver, but no significant alteration (p>0.05) in liver GST activity and GSH concentration. The results revealed that AQF and EAF of D. carrot seed possesses phytochemicals, which could be responsible for the enhancement of antioxidant defense system in vivo and alleviation of triton X-100 induced oxidative stress.

Effects of fermented rice bran on DEN-induced oxidative stress in mice: GSTP1, LINE-1 methylation, and telomere length ratio.

N-diethylnitrosamine (DEN), a well-known carcinogen, not only induces excessive reactive oxygen species but also suppresses DNA methylation. This study investigated the effect of fermented rice bran (FRB) treatment on DEN-induced oxidative stress through DNA methylation and telomere length analysis. To evaluate the potential protective role of FRB in oxidative stress, two different doses of FRB, DEN, and their combination were administered to mice that were preadapted or not to FRB. Glutathione-S-transferase P1 (GSTP1) methylation levels significantly decreased at 2 and 24hr after FRB and DEN co-administration in mice with and without pre-adaptation. Moreover, GSTP1 mRNA was upregulated under DEN-induced oxidative stress. Furthermore, changes in long interspersed nuclear element-1 methylation were observed from the viewpoint of genomic instability. In addition, FRB preadapted mice displayed a lower telomere length ratio than the non-adapted mice, suggesting that FRB adaptation offers advantages over the non-adapted conditions in terms of inflammation suppression. PRACTICAL APPLICATIONS: DEN induces excessive ROS, which is associated with oxidative stress on DNA and other cellular components, resulting in inflammation. This study shows that FRB may alleviate DEN-triggered oxidative stress, based on changes in GSTP1, LINE-1 methylation, and telomere length ratios, thereby, revealing the potential of dietary intervention during inflammation. Furthermore, this study furthers the current understanding of DNA methylation mechanisms underlying the antioxidant and anti-inflammatory effects of functional food components. These results indicate that dietary inclusion of FRB may help decrease oxidative DNA damage and its associated inflammation at early stages of a disease.

Bisdemethoxycurcumin inhibits oxidative stress and antagonizes Alzheimer's disease by up-regulating SIRT1.

IntroductionAlzheimer's disease (AD) is a progressive neurodegenerative disease. It can lead to progressive cognitive impairment, memory loss, and behavioral alterations. So far, the exact cellular and molecular mechanisms underlying this disorder remain unclear. And there are no effective treatments to prevent, halt, or reverse AD. In recent years, Chinese traditional medicine has become a new force in the treatment of AD, and the typical representatives of natural herbal ingredients are curcumin and its derivatives. Bisdemethoxycurcumin (BDMC), which is a classical derivative of curcumin, was found to have neuroprotective effects against a cell model of Alzheimer's disease (AD) in our previous studies. This study investigated the intrinsic mechanism of BDMC against AD in animal models.MethodsIn this study, BDMC was injected into the lateral ventricles of normal C57BL/6 mice, APP/PS mice, and APP/PS mice treated with EX527 (the inhibitor of SIRT1). Y maze and Morris water maze were used to test the learning and memory ability of mice. Nissl staining was used to observe the morphological changes of neurons. Immunofluorescence staining was used to detect Aβ deposition in mice. The activities of GSH and SOD were determined to observe the levels of oxidative stress in mice. And Western blot analyses were used to detect content of SIRT1 in mice.ResultsIn the APP/PS mice, after BDMC intervention, their cognitive function improved, oxidative stress adjusted, the number of neurons increased, Aβ deposition decreased, and the level of SIRT1 expression increased. However, when SIRT1 is inhibited, BDMC on the improvement in the learning and memory ability and the improvement on oxidative stress in APP/PS1 mice were reversed.ConclusionOur findings demonstrated that in the AD mice, BDMC has antagonistic effect on AD. And an intermediate step in the antagonism effect is caused by SIRT1 upregulation, which leading to decreased oxidative stress. Based on these, we concluded that BDMC injection into the lateral ventricle can act against AD by upregulating SIRT1 to antioxidative stress.

Neuroprotective Effects of Euonymus alatus Extract on Scopolamine-Induced Memory Deficits in Mice

Euonymus alatus is considered to elicit various beneficial effects against cancer, hyperglycemia, menstrual discomfort, diabetic complications, and detoxification. The young leaves of this plant are exploited as food and also utilized for traditional medicine in East Asian countries, including Korea and China. Our preliminary study demonstrated that ethanolic extract from the Euonymus alatus leaf (EAE) exhibited the strongest antioxidant enzyme-inducing activity among more than 100 kinds of edible tree leaf extracts. This study investigated whether EAE could attenuate the cognitive deficits caused by oxidative stress in mice. Oral intubation of EAE at 100 mg/kg bw or higher resulted in significant improvements to the memory and behavioral impairment induced via i.p. injection of scopolamine. Furthermore, EAE enhanced the expression levels of hippocampal neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor in mice, activated the Nrf2, and the downstream heme oxygenase-1 (HO-1) a quintessential antioxidant enzyme. As rutin (quercetin-3-O-rutinose) was abundantly present in EAE and free quercetin was able to induce defensive antioxidant enzymes in an Nrf2-dependent manner, our findings suggested that quercetin derived from rutin via the intestinal microflora played a significant role in the protection of the mouse hippocampus from scopolamine-induced damage through BDNF-mediated Nrf2 activation, thereby dampening cognitive decline.

X-Irradiation at 0.5Gy after the forced swim test reduces forced swimming-induced immobility in mice.

The forced swim test (FST) is a screening model for antidepressant activity; it causes immobility and induces oxidative stress. We previously reported that radon inhalation has antidepressant-like effects in mice potentially through the activation of antioxidative functions upon radon inhalation. This study aimed to investigate the effect of prior and post low-dose X-irradiation (0.1, 0.5, 1.0 and 2.0Gy) on FST-induced immobility and oxidative stress in the mouse brain, and the differences, if any, between the two. Mice received X-irradiation before or after the FST repeatedly for 5 days. In the post-FST-irradiated group, an additional FST was conducted 4h after the last irradiation. Consequently, animals receiving prior X-irradiation (0.1Gy) had better mobility outcomes than sham-irradiated mice; however, their levels of lipid peroxide (LPO), an oxidative stress marker, remained unchanged. However, animals that received post-FST X-irradiation (0.5Gy) had better mobility outcomes and their LPO levels were significantly lower than those of the sham-irradiated mice. The present results indicate that 0.5Gy X-irradiation after FST inhibits FST-induced immobility and oxidative stress in mice.

Juglanin administration protects skin against UVB‑induced injury by reducing Nrf2‑dependent ROS generation.

Extensive solar ultraviolet B (UVB) exposure of the skin results in inflammation and oxidative stress, which may contribute to skin cancer. Natural products have attracted attention for their role in the effective treatment of cutaneous neoplasia. Juglanin is purified from the crude extract of Polygonum aviculare, exhibiting anti-oxidant, anti-inflammatory and anti-cancer activities. Jugalanin was used in the current study to investigate whether it may ameliorate UVB irradiation-induced skin damage by reducing oxidative stress and suppressing the inflammatory response in vivo and in vitro. In the present study, hairless mice were exposed to UVB irradiation in the absence or presence of juglanin administration for 10 weeks. The findings indicated that juglanin inhibited UVB-induced hyperplasia and decreased infiltration in the skin of mice. UVB exposure-induced oxidative stress in mice and cells was inhibited by juglanin via enhancing anti-oxidant activity. Additionally, juglanin markedly reduced pro-inflammatory cytokine release, including cyclic oxidase 2, interleukin-1β and tumor necrosis factor-α, triggered by chronic UVB irradiation. Juglanin-ameliorated skin damage was associated with its suppression of mitogen activated protein kinases (MAPKs), including p38, extracellular signal regulated 1/2, and c-Jun N-terminal kinases, as well as nuclear factor (NF)-κB signaling pathways, which was dependent on nuclear factor-E2-related factor 2 (Nrf2)-modulated reactive oxygen species generation. Taken together, these data indicate that juglanin protected against UVB-triggered oxidative stress and inflammatory responses by suppressing MAPK and NF-κB activation via enhancing Nrf2 activity.

Processed velvet antler: nutritional profile, in vitro antioxidant capacities, and alleviating symptoms of kidney-yang deficiency in mice

We present the nutritional composition, antioxidant activity, and pharmacological effects of three processed velvet antler products [antler powder (AP), antler slice (AS), and honey antler slice (HAS)] prepared in our laboratory. The nutrient profile of crude protein, fatty acids, amino acids, mineral elements, and nucleosides were established. The antioxidant activity was measured. The effects of three extracts on kidney-yang deficiency, induced by hydrocortisone, in mice were investigated. The nutrition composition of HAS was relatively low owing to its high moisture. AP, AS, and HAS extracts all exhibited concentration-dependent activity in DPPH*, ABTS, and FARP antioxidant assays. HAS had similar effect with AP and AS in improving oxidative stress in mice with kidney-yang deficiency, moreover, it could improve the serum cAMP level much significantly than the others. The processing without repeated heating might contribute in preserving more bioactive components in HAS, which could be the explanation of its excellent efficiency in relieving kidney-yang deficiency.

TGF‐β Signaling Regulates SLC8A3 Expression and Oxidative Stress in Mouse Developing Dopaminergic Neurons

Calcium homeostasis is a cellular process required for proper cell function and survival, and maintained by the coordinated action of several transporters, among them members of the NCX family, such as SLC8A3, the isoform 3 of the Na+/Ca2+ exchanger (NCX3). Transforming growth factor beta (TGF‐β) signaling belongs to signaling cascades defining development and survival of several neuronal groups and known to regulate several channels and transporters. We have generated a conditional knockout mouse with cell‐type specific deletion of TGF‐β signalling from Engrailed 1 (En1) expressing cells, i.e. in cells derived from rhombomere r1. Subsequently, we have investigated regulation of SLC8A3, and elucidated the underlying molecular mechanisms. The results show that SLC8A3 expression is significantly downregulated in developing dopaminergic and serotonergic neurons from mutant mice and that low SLC8A3 abundance prevents the expression of the anti‐apoptotic Bcl‐xL. We also show that TGF‐β signaling regulates SLC8A3 expression via the canonical (Smad‐dependent) and MAPK signaling pathways and chromatin immunoprecipitation has revealed that TGF‐β signaling directly regulates transcription of Slc8a3 through binding of Smad4 to the Slc8a3 promoter. Moreover, expression of the lipid peroxidation markers malondialdehyde (MDA) and 4‐hydroxynonenal (4HNE) was upregulated in dopaminergic neurons lacking TGF‐β signaling. These results suggest that TGF‐β signaling regulates SLC8A3 expression in developing dopaminergic and serotonergic neurons thereby preventing oxidative stress.Support or Funding InformationDeutsche Forschungsgemeinschaft (DFG) [Kr1477/10‐3]

Time‐dependent induction of vascular oxidative stress, inflammation, endothelial dysfunction and high blood pressure by aircraft noise exposure in mice

BackgroundTransportation noise is recognized as an important cardiovascular risk factor. It was shown that traffic noise exposure is associated with cerebro/cardiovascular diseases such as hypertension, myocardial infarction, and stroke. Aircraft noise causes endothelial dysfunction, inflammation and increases cerebral/cardiovascular oxidative stress in mice and traffic noise in general increased stroke mortality in large population studies. Chronic aircraft noise also causes learning and memory impairment in children. We recently studied the effects of different time exposure protocols (sleep versus awake phase) of aircraft noise exposure on C57Bl/6JRj mice and demonstrated that sleep phase noise exposure impairs the circadian clock and causes oxidative stress, endothelial dysfunction and high blood pressure.Methods and ResultsBefore the main study, we ensured that the longest noise exposure did not cause hearing loss in the mice by using audiometry. C57Bl/6JRj mice were exposed to aircraft noise for 4, 7, 14 and 28 days at a maximum sound level of 85 dB(A) and a mean sound pressure level of 72 dB(A) and compared with unexposed control mice. The induction of endothelial dysfunction and elevation of blood pressure was comparable in all exposure groups. Oxidative burst in the whole blood, stimulated with phorbol 12,13‐dibutyrate (PDBu) or zymosan A, was increased in all exposed groups with a maximum at 4 or 7 days. Vascular ROS formation as envisaged by dihydroethidium (DHE) staining was increased in noise‐exposed mice without a significant time response. Noise‐induced aortic, cardiac and cerebral superoxide formation as measured by DHE HPLC analysis increased in dependence of noise exposure duration. Similarly, levels of interleukin‐6 (IL‐6) were time dependently increased by trend in plasma and brain tissue in all noise exposed mice. We also established increased NOX‐2 expression in aortic tissue of noise exposed mice, while levels of P‐VASP were decreased after exposure.ConclusionWe here present novel data on the effects of different aircraft noise exposure protocols (4–28 days) indicating that most adverse vascular effects are established already after 4 days. Importantly, our present data prove that the applied moderate noise levels do not cause induction of hearing loss, even not after long‐term exposures. Thus our present data provide important technical insights in noise exposure protocols for future translational studies in mice with relevance for the human situation.Support or Funding InformationOur experimental studies on noise effects in mice were supported by vascular biology research grants from the Boehringer Ingelheim Foundation for the collaborative research group „Novel and neglected cardiovascular risk factors: molecular mechanisms and therapeutic implications” and Foundation Heart of Mainz

D-ribose-L-cysteine enhances memory task, attenuates oxidative stress and acetyl-cholinesterase activity in scopolamine amnesic mice.

d-Ribose-l-cysteine (DRLC) is an analogue of cysteine that has been shown to boost cellular antioxidant capacity by enhancing intracellular biosynthesis of glutathione (GSH). Deficiency of GSH has been implicated in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder associated with loss of memory. Thus, the use of antioxidants to prevent or retard the progression of memory deteriorations in persons with AD has been the focus of intense investigations. This study was carried out to evaluate the effects of DRLC on memory and scopolamine-induced amnesia, acetyl-cholinesterase activity, and oxidative stress in mice. Male Swiss mice were given oral administration of saline (10 ml/kg), DRLC (25, 50, and 100 mg/kg) or donepezil (1 mg/kg) 30 min before testing for memory performance using Y-maze and object recognition models. Another set of mice were also pretreated orally with saline, DRLC (25, 50, and 100 mg/kg) or donepezil (1 mg/kg) but in combination with scopolamine (3 mg/kg, i.p.) daily for 7 days. Thirty minutes after treatment on Day 7, memory function was then evaluated. The brain levels of acetyl-cholinesterase and oxidative stress parameters were assayed. DRLC significantly (p < .05) enhanced memory performance and attenuated scopolamine-induced amnesia. Increased acetyl-cholinesterase activity and oxidative stress, as shown by decreased antioxidant substrates (glutathione and catalase) and elevated malondialdehyde contents in mice with scopolamine amnesia were also attenuated by DRLC. Our findings suggest that inhibition of oxidative stress and acetyl-cholinesterase activity might contribute to the potential benefit of DRLC in persons with amnesia.

The Protective effect of Crocin on Ovary Mast cells, Blood Vessels and Ovary, Serum Biochemical changes following Busulfan-induced Oxidative Stress in Mice.

هدف: هدف این مطالعه ارزیابی اثرات محافظتی کروسین بر ماست‏سل­ها و عروق خونی و تغییرات بیوشیمیایی تخمدان و سرم در موش‌های درمان شده با بوسولفان می‏باشد.مواد و روش‏ها: در این مطالعه تجربی30 سر موش نژاد NMRI در6 گروه مساوی در یک دوره 21 روزه مورد مطالعه قرار گرفتند. گروه کنترل سالم، حلال بوسولفان به حجم 1/0 میلی لیتر و گروه بوسولفان، فقط بوسولفان با دوز 10 میلی‏گرم بر کیلوگرم تک دوز دریافت کردند. گروه‌های تجربی شماره 1،2،3 کروسین را به‏ترتیب با دوزهای 100،200،400 میلی‏گرم بر کیلوگرم روزانه به‏همراه بوسولفان با دوز 10 میلی‏گرم بر کیلوگرم تک دوز دریافت نمودند. گروه کنترل مثبت، کروسین با دوز 400 میلی‏گرم برکیلوگرم روزانه دریافت نمود. پایان دوره تخمدان چپ موش‏ها جهت مطالعه ماست‏سل‏ها و عروق خونی و تخمدان راست و سرم خونشان جهت ارزیابی‏های بیوشیمیایی مورد استفاده قرار گرفتند. دادههای حاصله با استفاده از نرم افزار SSPS و روش آماری AVONA یک طرفه و تست تعقیبی yekuT مورد مقایسه قرار گرفتند و اختلاف در سطح 5/0>p معنی‌دار توصیف شد.نتایج: نتایج نشان داد بوسولفان باعث افزایش معنی‌دار ماست‏سل­ها (011/0p=) و کاهش معنی‏دار عروق خونی (009/0p=) و افزایش معنی‌دار مالون‏دی‏آلدئید (000/0p=) و کاهش معنی‏دار آنزیم سوپراکسید دیسموتاز (000/0p=) نسبت به گروه کنترل شد، در حالی‏که کروسین در تمامی دوزهای مورد استفاده در مطالعه حاضر به‏خصوص در دوز 200 میلی‏گرم بر کیلوگرم به‏طور قابل توجهی آثار نامطلوب بوسولفان را تعدیل نمود.نتیجه‏گیری: متعاقب این تحقیق مشخص شدکه کروسین به‏علت خاصیت آنتی‏اکسیدانتی می‏تواند به‏طور قابل توجهی عوارض سوء بوسولفان را کاهش دهد.

Allium cepa fraction attenuates STZ-induced dementia via cholinesterase inhibition and amelioration of oxidative stress in mice.

Background An earlier study demonstrated significant antioxidant and anticholinesterase activities of hydromethanol extract (HME) of Allium cepa. The aim of the study was to investigate the component responsible for these activities followed by an in vivo study. Methods In vitro antioxidant and anticholinesterase activities of standardized ethylacetate fraction (EAF) of HME were assessed. Bioactivity-guided fractionation showed that, as compared with its subfractions, EAF had most significant activity in 2,2-diphenyl-1-picrylhydrazyl and Ellman assays. Thus, EAF was further examined using a streptozotocin (STZ)-induced model of Alzheimer's disease in mice. STZ was injected intracerebroventricularly on days 1 and 3 (3 mg/kg) in mice. EAF was thereafter administered (42, 84, and 168 mg/kg b.w./day p.o.) from days 9 to 22. The Morris water maze test was used to evaluate learning and memory in mice. Acetylcholinesterase (AChE) activity and oxidative stress markers were assessed in the brain homogenates of mice. Additionally, histopathological studies were performed to observe effects in the brain at the cellular level. EAF was standardized based on quercetin and quercetin 4'-O-glucoside content using a validated thin layer chromatography densitometric method. Results STZ produced significant (p < 0.05) memory impairment along with oxidative stress and a cholinergic deficit in mice. EAF treatment ameliorated STZ-induced behavioral deficits and biochemical alterations in mice in a significant and dose-dependent manner. Conclusions Our results show that EAF is efficacious in improving memory and learning via AChE inhibition and antioxidant activity in the mice brain. Thus, AC could be explored further to find out a lead candidate for Alzheimer's disease.

Protective Effects of Anethum graveolens Seed's Oil Nanoemulsion Against Cadmium-Induced Oxidative Stress in Mice.

The cadmium (Cd) is a toxic heavy metal that induces oxidative stress in both humans and animals. The plant phenolic compounds are capable of alleviating the toxicity of heavy metals. The encapsulation of plant bioactive compounds using nanoemulsion technology could enhance their bioefficacy. In this study, the protective effects of Anethum graveolens seed's oil nanoemulsion (AGN) against cadmium-induced oxidative stress in mice were studied. The results showed that the major bioactive compounds of essential oil were carvone and limonene. The result of particle size analysis revealed the pseudo-spherical droplets with nanometer size (148.8 ± 9.48nm), homogenous dispersion, and physical colloidal stability. The Cd intoxication in mice (5mg/kg BW for 30days) reduced the body weight gain; however, treatment of the mice with different concentration of AGN (0.125, 0.25, and 0.5mg/L, 30days) through drinking water improved the body weight loss, liver Cd deposition, lipid peroxidation, cellular antioxidant redox potential, and inflammation in the liver, kidney, and brain of the mice challenged by cadmium-induced oxidative stress. The results of the present study revealed that drinking the essential oil of Anethum graveolens nanoemulsion containing carvone and limonene could be a promising strategy to protect the tissues against cadmium-induced oxidative damage.

Chia Seed Oil Prevents High Fat Diet Induced Hyperlipidemia and Oxidative Stress in Mice

AbstractHyperlipidemia is a common cardiovascular disease. At present, the influence of high fat diet (HFD) on this is being explored. Recently, vegetable oils rich in omega‐3 have been reported that can treat hyperlipidemia caused by HFD. However, the effects of chia seed oil (CSO) on HFD‐induced hyperlipidemia and oxidative stress are poorly studied. Hence, in this study, the effects of CSO on hyperlipidemia and oxidative stress induced by HFD in mice are analyzed by various commercial kits, section staining, and protein expression. The results show that CSO decreases body weight and organ index. Meanwhile, CSO reduces serum lipid levels of total cholesterol, triglyceride, and low‐density lipoprotein cholesterol. It can also elevate superoxide dismutase and glutathione peroxidase activities and reduce malondialdehyde content in serum and liver. The results of histopathological analysis prove that CSO improves hepatic steatosis and reduces lipid deposition. Further, the results of western blot demonstrate that CSO upregulates the expression of peroxisome proliferator‐activated receptor alpha and carnitine palmitoyltransferase 1a in the liver. As a result, CSO may be a potential lipid‐lowering oil to prevent and treat HFD‐induced hyperlipidemia and oxidative stress.Practical Applications CSO, as a byproduct of chia seed processing, is a rich source of α‐linolenic acid. This study investigates the effects of CSO on HFD‐induced hyperlipidemia and oxidative stress in mice. It is concluded that dietary CSO can improve the hyperlipidemia in HFD‐induced mice via analysis of lipid parameters, histopathology study of the liver, and lipid metabolism related genes. In addition, supplementation of CSO also can improve the oxidative stress in mice. Therefore, CSO can be used for the prevention of hyperlipidemia and oxidative stress. This research provides a theoretical basis for the comprehensive development and utilization of functional chia seed oil.