Changes in Antioxidant Enzymes Activities and Lipid Peroxidase Level in Tissues of Stress-induced Rats

Background: Estimating the changes in the levels of oxidative stress biomarkers are vital in identifying stress related disease in living organism. This study examined changes in the activity of antioxidant enzymes and lipid peroxidase level in female Wistar rats exposed to stressors of different nature were examined. Methods: 88 apparently healthy rats within the ages of 8-12weeks and weighing between 120-180g were utilized for the study. Rats were acclimatized for 2weeks and fed with rat chaw and water ad libitum. Animals were stressed at the rate of 1hr, 3hr or 5hr per day for 1, 2 or 3weeks respectively. After the experimental protocol of stress induction, the rats werekilled via cervical dislocation and some vital organs were carefully harvested for tissue homogenates in assessing SOD, CAT and MDA antioxidants. Data collected were analyzed using Mean±SEM, ANOVA was used to compare means and LSD was used for post hoc. Results: SOD activity of the different tissues examined were significantly (p<0.05) altered irrespective of the stressor applied especially in the restraint or intruder stressors. CAT activity were significantly (p<0.05) reduced in all stressors irrespective of the rate of exposure. The study also revealed that lipid peroxidase levels were significantly (p<0.05) increased in all tissues irrespective of the rate of exposure and type of stressor applied. Conclusions: The findings validate the ability of the stressors to increase production of free radicals, thus, changes in antioxidant enzymes activities and lipid peroxidase level implies compromised cellular activity in tissues of stress-induced rats.

Thymoquinone Lowers Blood Glucose and Reduces Oxidative Stress in a Rat Model of Diabetes

The aim of the present study was to assess the short-term effects of Thymoquinone (TQ) on oxidative stress, glycaemic control, and renal functions in diabetic rats. DM was induced in groups II and III with a single dose of streptozotocin (STZ), while group I received no medication (control). The rats in groups I and II were then given distilled water, while the rats in group III were given TQ at a dose of 50 mg/kg body weight/day for 4 weeks. Lipid peroxidase, nitric oxide (NO), total antioxidant capacity (TAC), glycated haemoglobin (HbA1c), lipid profiles, and renal function were assessed. Moreover, the renal tissues were used for histopathological examination. STZ increased the levels of HbA1c, lipid peroxidase, NO, and creatinine in STZ-induced diabetic rats in comparison to control rats. TAC was lower in STZ-induced diabetic rats than in the control group. Furthermore, rats treated with TQ exhibited significantly lower levels of HbA1c, lipid peroxidase, and NO than did untreated diabetic rats. TAC was higher in diabetic rats treated with TQ than in untreated diabetic rats. The histopathological results showed that treatment with TQ greatly attenuated the effect of STZ-induced diabetic nephropathy. TQ effectively adjusts glycaemic control and reduces oxidative stress in STZ-induced diabetic rats without significant damaging effects on the renal function.

Activation of Cytochrome C Peroxidase Function Through Coordinated Foldon Loop Dynamics upon Interaction with Anionic Lipids

ABSTRACTCardiolipin (CL) is a mitochondrial anionic lipid that plays important roles in the regulation and signaling of mitochondrial apoptosis. CL peroxidation catalyzed by the assembly of CL-cytochrome c (cyt c) complexes at the inner mitochondrial membrane is a critical checkpoint. The structural changes in the protein, associated with peroxidase activation by CL and different anionic lipids, are not known at a molecular level. To better understand these peripheral protein-lipid interactions, we compare how phosphatidylglycerol (PG) and CL lipids trigger cyt c peroxidase activation, and correlate functional differences to structural and motional changes in membrane-associated cyt c. Structural and motional studies of the bound protein are enabled by magic angle spinning solid state NMR spectroscopy, while lipid peroxidase activity is assayed by mass spectrometry. PG binding results in a surface-bound state that preserves a nativelike fold, which nonetheless allows for significant peroxidase activity, though at a lower level than binding its native substrate CL. Lipid-specific differences in peroxidase activation are found to correlate to corresponding differences in lipid-induced protein mobility, affecting specific protein segments. The dynamics of omega loops C and D are upregulated by CL binding, in a way that is remarkably controlled by the protein:lipid stoichiometry. In contrast to complete chemical denaturation, membrane-induced protein destabilization reflects a destabilization of select cyt c foldons, while the energetically most stable helices are preserved. Our studies illuminate the interplay of protein and lipid dynamics in the creation of lipid peroxidase-active proteolipid complexes implicated in early stages of mitochondrial apoptosis.GRAPHICAL ABSTRACTHIGHLIGHTSA mitochondrial protein-lipid complex regulates lipid peroxidation in apoptosis.Peroxidase-active lipid-cytochrome c complexes are reconstituted in vitro.Phosphatidylglycerol lipids are less effective activators than cardiolipin.Activity correlates to localized dynamics, distinct from chemical denaturation.A dynamic interplay of cytochrome c foldons and anionic lipids regulate activity.

Formulation and Evaluation of Polyherbal Cream Containing Cinnamomum zeylanicum Blume, Glycyrrhiza glabra L and Azadirachta indica A. Juss. Extracts to Topical Use

Alcoholic extracts of medicinal plants Cinnamomum zeylanicum Blume, Glycyrrhiza glabra L, and Azadirachta indica A. Juss were subjected to the evaluation of antioxidant properties and combined for the cream formulation. The antioxidant property was determined by using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay and inhibition of lipid peroxidase assays. The cream formulation was designed using Minitab software and a central composite design was used to study the effect of dependent variables, steric acid and cetyl alcohol on the response variables such as, viscosity, pH, and spreadability. The phytochemical screening of extracts showed the presence of tannin, phenol, flavonoids, saponins, and alkaloids. Antioxidant properties of the extracts and their relative composition were found variable. Composition F3 (C. zeylanicum Blume: G. glabra L: A. indica A. Juss; 01: 02: 01) possessed the highest antioxidant capacity compared to other ratios. The cream prepared from this composition was found stable for pH, viscosity as well as antioxidant activity under normal condition (25) and accelerated condition (40 ). The cream with DPPH scavenging activity of 93.86 % at 15 µg/mL (IC50 8.58±0.30) and lipid peroxidase assay 90.93 % at 200 µg/mL (IC50 72.30±0.60) with pH 5.50 was found with a non-Newtonian positive thixotropic flow property. Parameters like pH, viscosity, and spreadability of the cream were within the acceptance range, and found stable and permeable

Pengaruh suplementasi ferro sulfat terhadap kadar low density lipoprotein dan high density lipoprotein pada tikus bunting

Latar Belakang: Penambahan kebutuhan zat besi selama kehamilan digunakan untuk pertumbuhan janin dan plasenta serta penambahan volume darah ibu sebagai persiapan persalinan. Pemberian tablet tambah darah untuk mencegah anemia pada ibu hamil diberikan minimal 90 tablet selama kehamilan atau setara dengan elemen besi sebesar 60 mg tiap tabletnya. Namun, sebuah studi menyatakan bahwa pemberian suplementasi besi dosis 50–60 mg/hari (150–185 mg/hari fero sulfat) pada wanita hamil berisiko menyebabkan hemokonsentrasi, preeklamsia, dan diabetes gestasional. Suplemen zat besi serta peningkatan cadangan zat besi dalam darah dikaitkan dengan komplikasi pada ibu hamil dan peningkatan stres oksidatif yang menyebabkan peningkatan lipid peroxidase selama kehamilan. Tujuan: Penelitian ini bertujuan untuk mengetahui pengaruh suplementasi ferro sulfat terhadap kadar LDL dan HDL pada tikus bunting. Metode: Desain penelitian yang digunakan adalah post test only control group design. Sampel adalah 25 ekor tikus yang dibagi menjadi lima kelompok, yaitu kelompok tikus bunting normal, tikus bunting anemia, tikus bunting anemia yang diberi ferro sulfat selama 18 hari, tikus bunting anemia yang diberi ferro sulfat selama 12 hari, dan tikus bunting anemia yang diberi ferro sulfat selama 6 hari. Pemeriksaan parameter dilakukan pada hari ke-18 kebuntingan. Analisis data dilakukan dengan uji One Way ANOVA lalu dilanjutkan uji post hoc Fisher’s Least Significant Different (LSD) menggunakan software SPSS 20. Hasil: Lama waktu pemberian ferro sulfat berpengaruh terhadap kadar LDL dan HDL tikus bunting anemia (p<0,001). Kesimpulan: Lama waktu suplementasi ferro sulfat akan meningkatkan kadar LDL dan menurunkan kadar HDL pada tikus bunting model anemia.

EXPLORATION OF IN VIVO ANTIOXIDANT ACTIVITY OF 50% ETHANOLIC EXTRACT OF SESAMUM INDICUM L. SEED AGAINST HIGH FAT DIET INDUCED RATS

Objective: The aim of the present study was to investigate the in vivo antioxidant potential of 50% ethanolic extract of Sesamum indicum against high-fat diet-induced rats. Methods: Animals were treated with plant extract for 30 d, and a high-fat diet was given to all groups except plain control, throughout, out the study. And alpha-tocopherol acetate (Vit, E) was used as standard. Pre-treatment with 16 mg/100 gm of body weight of 50% ethanolic extract of Sesamum indicum improved the Superoxide dismutase, catalase, glutathione, and lipid peroxidation levels significantly as compared to control group. Results: The present studies revealed that Sesamum indicum has significant in vivo antioxidant activity and can be used to protect tissue from oxidative stress. The result showed that the activities of SOD, catalase, lipid peroxidase, and glutathione, in the group treated with high-fat diet declined significantly than that of normal group. Conclusion: 50% ethanolic extract of in the dose of Sesamum indicum 16 mg/100 gm of body weight, has improved the SOD, catalase, glutathione, and lipid peroxidase levels significantly, which were comparable with high-fat-diet-induced rats. Based on this study we conclude that the 50% ethanolic extract of Sesamum indicum possesses in vivo antioxidant activity and can be employed in protecting tissue from oxidative stress.

Therapeutic Role of Transcranial Direct Current Stimulation in Alzheimer Disease Patients: Double-Blind, Placebo-Controlled Clinical Trial

Objective. To explore the neuropsychological effects and levels of tau protein (TAU), amyloid β 1-42 (Aβ 1-42), and lipid peroxidase after 10 sessions of anodal transcranial direct current stimulation (tDCS) in patients with mild to moderate Alzheimer disease (AD). Patients and methods. A total of 46 consecutive patients with probable AD participated in this study. They were classified randomly into 2 equal groups: active versus sham. Each patient received 10 sessions of anodal tDCS over the left and right temporoparietal region for 20 minutes for each side with the cathode on the left arm. Patients were assessed using the Modified Mini Mental State Examination (MMMSE), clock drawing test, Montreal Cognitive Scale (MoCA), and the Cornell Scale for depression. Serum TAU, Aβ 1-42, and lipid peroxidase were measured before and after the 10th session. Results. There was a significant improvement in the total score of each cognitive rating scale (MMMSE, clock drawing test, and MoCA) in the real group, whereas no such change was observed in the sham group. The Cornell depression score improved significantly in both groups. There was a significant increase in serum Aβ 1-42 ( P = .02) in the real but not in the sham group, with a significant Treatment condition × Time interaction ( P = .009). There was no significant effect on tau or lipid peroxidase in either group but a significant positive correlation between changes of Aβ1-42 and MMMSE ( P = .005) and MoCA ( P = .02). Conclusion. The observed cognitive improvements were complemented by parallel changes in serum levels of Aβ 1-42.

Targeting a Therapy-Resistant Cancer Cell State Using Masked Electrophiles as GPX4 Inhibitors

SUMMARYWe recently discovered that inhibition of the lipid peroxidase GPX4 can selectively kill cancer cells in a therapy-resistant state through induction of ferroptosis. Although GPX4 lacks a conventional druggable pocket, covalent small-molecule inhibitors are able to overcome this challenge by reacting with the GPX4 catalytic selenocysteine residue to eliminate enzymatic activity. Unfortunately, all currently-reported GPX4 inhibitors achieve their activity through reactive chloroacetamide groups. We demonstrate that such chloroacetamide-containing compounds are poor starting points for further advancement given their promiscuity, instability, and low bioavailability. Development of improved GPX4 inhibitors, including those with therapeutic potential, requires the identification of new electrophilic chemotypes and mechanisms of action that do not suffer these shortcomings. Here, we report our discovery that nitrile oxide electrophiles, and a set of remarkable chemical transformations that generates them in cells from masked precursors, provide an effective strategy for selective targeting of GPX4. Our results, which include structural insights, target engagement assays, and diverse GPX4-inhibitor tool compounds, provide critical insights that may galvanize development of improved compounds that illuminate the basic biology of GPX4 and therapeutic potential of ferroptosis induction. In addition, our discovery that nitrile oxide electrophiles engage in highly selective cellular interactions and are bioavailable in their masked forms may be relevant for targeting other currently undruggable proteins, such as those revealed by recent proteome-wide ligandability studies.