Mesoporous Polydopamine Nanoparticles Attenuate Morphine Tolerance in Neuropathic Pain Rats by Inhibition of Oxidative Stress and Restoration of the Endogenous Antioxidant System

Oxidative stress resulting from reactive oxygen species (ROS) is known to play a key role in numerous neurological disorders, including neuropathic pain. Morphine is one of the commonly used opioids for pain management. However, long-term administration of morphine results in morphine antinociceptive tolerance (MAT) through elevation of ROS and suppression of natural antioxidant defense mechanisms. Recently, mesoporous polydopamine (MPDA) nanoparticles (NPS) have been known to possess strong antioxidant properties. We speculated that morphine delivery through an antioxidant nanocarrier might be a reasonable strategy to alleviate MAT. MPDAs showed a high drug loading efficiency of ∼50%, which was much higher than conventional NPS. Spectral and in vitro studies suggest a superior ROS scavenging ability of NPS. Results from a rat neuropathic pain model demonstrate that MPDA-loaded morphine (MPDA@Mor) is efficient in minimizing MAT with prolonged analgesic effect and suppression of pro-inflammatory cytokines. Additionally, serum levels of liver enzymes and levels of endogenous antioxidants were measured in the liver. Treatment with free morphine resulted in elevated levels of liver enzymes and significantly lowered the activities of endogenous antioxidant enzymes in comparison with the control and MPDA@Mor-treated group. Histopathological examination of the liver revealed that MPDA@Mor can significantly reduce the hepatotoxic effects of morphine. Taken together, our current work will provide an important insight into the development of safe and effective nano-antioxidant platforms for neuropathic pain management.

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Evaluation of the Potential Cardioprotective Activity of Some Saudi Plants against Doxorubicin Toxicity

Zeitschrift für Naturforschung C ◽

10.1515/znc-2012-5-609 ◽

2012 ◽

Vol 67 (5-6) ◽

pp. 297-307 ◽

Cited By ~ 6

Author(s):

Osama M. Ashour ◽

Ashraf B. Abdel-Naim ◽

Hossam M. Abdallah ◽

Ayman A. Nagy ◽

Ahmed M. Mohamadin ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Activities ◽

Histopathological Examination ◽

Antioxidant Properties ◽

Radical Scavenging ◽

Serum Markers ◽

Protective Effects ◽

Medicinal Uses ◽

Cordia Myxa

Doxorubicin (DOX) is an anthracycline antibiotic widely used as a chemotherapeutic agent in the treatment of several tumours. However, its cardiac toxicity limits its use at maximum therapeutic doses. Most studies implicated increased oxidative stress as the major determinant of DOX cardiotoxicity. The local Saudi flora is very rich in a variety of plants of quite known folkloric or traditional medicinal uses. Tribulus macropterus Boiss., Olea europaea L. subsp. africana (Mill.) P. S. Green, Tamarix aphylla (L.) H. Karst., Cynomorium coccineum L., Cordia myxa L., Calligonum comosum L’ Hér, and Withania somnifera (L.) Dunal are Saudi plants known to have antioxidant activities. The aim of the current study was to explore the potential protective effects of methanolic extracts of these seven Saudi plants against DOX-induced cardiotoxicity in rats. Two plants showed promising cardioprotective potential in the order Calligonum comosum > Cordia myxa. The two plant extracts showed potent in vitro radical scavenging and antioxidant properties. They significantly protected against DOX-induced alterations in cardiac oxidative stress markers (GSH and MDA) and cardiac serum markers (CK-MB and LDH activities). Additionally, histopathological examination indicated a protection against DOX-induced cardiotoxicity. In conclusion, C. comosum and C. myxa exerted protective activity against DOX-induced cardiotoxicity, which is, at least partly, due to their antioxidant effect

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Antioxidant properties of antiepileptic drugs levetiracetam and clonazepam in mice brain after in vitro-induced oxidative stress

African Journal of Pharmacy and Pharmacology ◽

10.5897/ajpp2015.4358 ◽

2016 ◽

Vol 10 (14) ◽

pp. 278-288 ◽

Cited By ~ 2

Author(s):

de Albuquerque Oliveira Aline ◽

Isabel Linhares Maria ◽

Jos eacute Maia Chaves Filho Adriano ◽

Ricardo Vasconcelos Rios Emiliano ◽

Nayane de Carvalho Lima Camila ◽

...

Keyword(s):

Oxidative Stress ◽

Antiepileptic Drugs ◽

Antioxidant Properties ◽

Mice Brain

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Aminoguanidine Protects Boar Spermatozoa against the Deleterious Effects of Oxidative Stress

Pharmaceutics ◽

10.3390/pharmaceutics10040212 ◽

2018 ◽

Vol 10 (4) ◽

pp. 212 ◽

Cited By ~ 7

Author(s):

Eliana Pintus ◽

Martin Kadlec ◽

Marija Jovičić ◽

Markéta Sedmíková ◽

José Ros-Santaella

Keyword(s):

Oxidative Stress ◽

Therapeutic Agent ◽

Antioxidant Properties ◽

In Vitro Effects ◽

Oxide Synthase ◽

Boar Spermatozoa ◽

Generating System ◽

Control Samples ◽

Inducible Nitric Oxide

Aminoguanidine is a selective inhibitor of the inducible nitric oxide synthase (iNOS) and a scavenger of reactive oxygen species (ROS). Numerous studies have shown the antioxidant properties of aminoguanidine in several cell lines, but the in vitro effects of this compound on spermatozoa under oxidative stress are unknown. In this study, we tested the hypothesis that aminoguanidine may protect against the detrimental effects of oxidative stress in boar spermatozoa. For this purpose, sperm samples were incubated with a ROS generating system (Fe2+/ascorbate) with or without aminoguanidine supplementation (10, 1, and 0.1 mM). Our results show that aminoguanidine has powerful antioxidant capacity and protects boar spermatozoa against the deleterious effects of oxidative stress. After 2 h and 3.5 h of sperm incubation, the samples treated with aminoguanidine showed a significant increase in sperm velocity, plasma membrane and acrosome integrity together with a reduced lipid peroxidation in comparison with control samples (p < 0.001). Interestingly, except for the levels of malondialdehyde, the samples treated with 1 mM aminoguanidine did not differ or showed better performance than control samples without Fe2+/ascorbate. The results from this study provide new insights into the application of aminoguanidine as an in vitro therapeutic agent against the detrimental effects of oxidative stress in semen samples.

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The Enhanced Beneficial Effect of Extra Virgin Olive Oil Over Evening Primrose Oil on Oxidative Stress, and Liver Function in Male Arthritic Rats

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i32a31712 ◽

2021 ◽

pp. 14-26

Author(s):

Mohamed A. Kandeil ◽

Sana’a O. Ebrahim ◽

Basant M. Mahmoud

Keyword(s):

Rheumatoid Arthritis ◽

Oxidative Stress ◽

Olive Oil ◽

Liver Enzymes ◽

Virgin Olive Oil ◽

Antioxidant Properties ◽

Extra Virgin Olive Oil ◽

Male Rats ◽

Evening Primrose Oil ◽

Evening Primrose

Aims: Rheumatoid arthritis (RA) is characterized by the onset of oxidative stress. This study aimed to evaluate the enhancing of extra virgin olive (EVOO) and Evening primrose oil (EPO) on oxidative stress and liver enzymes in male Wistar rats and compare between them. Place and Duration: Faculty of Science biochemistry department, Between July 2018 and August 2018. Methodology: A Subcutaneous injection of 200 µl of Freund's complete adjuvant into a footpad of the right hind leg of Wistar male rats at two consecutive days induced RA. Rats received EVOO and EPO daily by oral gavage needle with gauge 18 at doses of 5 mg/kg b.wt./day. for 10 and 21 days. No loss was recorded in the experimental rats. Results: A significant depletion in serum Reduced glutathione content (GSH), glutathione peroxidase (GPX), and glutathione s transferase activities (GST) in arthritic rats compared to normal rats after 10 and 21 days of induction which improved significantly after 10 and 21 days of EPO and EVOO treatments. EPO and EVOO treatments for 21 days increased the GSH and GPX compared to 10 days treatments while no difference in GST activity. EVOO treatment improved GSH and GPX after 10 and 21 days than EPO treatment. The elevated uric acid levels in arthritic rats were markedly ameliorated as a result of EVOO and EPO treatment administration. Increased lipid peroxidation products (MDA), rheumatoid factor, and liver enzyme (Alanine transaminase ALT and Aspartate transaminase AST) were recorded in arthritic rats and they significantly progressed after EPO and EVOO treatments for 10 and 21 days but EVOO had the best effect at 21 days. Conclusion: EVOO and EPO showed significant antioxidant efficacies and improved affected liver enzymes due to rheumatoid arthritis onset. When comparing olive oil has more antioxidant properties than evening primrose oil, so we recommend more studies on olive oil combination with anti-arthritic medications to improve their efficacies with less toxicity.

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Revisiting the Oxidation of Flavonoids: Loss, Conservation or Enhancement of Their Antioxidant Properties

Antioxidants ◽

10.3390/antiox11010133 ◽

2022 ◽

Vol 11 (1) ◽

pp. 133

Author(s):

Hernan Speisky ◽

Fereidoon Shahidi ◽

Adriano Costa de Camargo ◽

Jocelyn Fuentes

Keyword(s):

Antioxidant Capacity ◽

Antioxidant Properties ◽

Oxidative Modification ◽

Oxygen Species ◽

Ros Scavenging ◽

High Susceptibility ◽

Comprehensive Description ◽

Health Promoting ◽

Endogenous Antioxidant ◽

Electrophilic Character

Flavonoids display a broad range of health-promoting bioactivities. Among these, their capacity to act as antioxidants has remained most prominent. The canonical reactive oxygen species (ROS)-scavenging mode of the antioxidant action of flavonoids relies on the high susceptibility of their phenolic moieties to undergo oxidation. As a consequence, upon reaction with ROS, the antioxidant capacity of flavonoids is severely compromised. Other phenol-compromising reactions, such as those involved in the biotransformation of flavonoids, can also markedly affect their antioxidant properties. In recent years, however, increasing evidence has indicated that, at least for some flavonoids, the oxidation of such residues can in fact markedly enhance their original antioxidant properties. In such apparent paradoxical cases, the antioxidant activity arises from the pro-oxidant and/or electrophilic character of some of their oxidation-derived metabolites and is exerted by activating the Nrf2–Keap1 pathway, which upregulates the cell’s endogenous antioxidant capacity, and/or, by preventing the activation of the pro-oxidant and pro-inflammatory NF-κB pathway. This review focuses on the effects that the oxidative and/or non-oxidative modification of the phenolic groups of flavonoids may have on the ability of the resulting metabolites to promote direct and/or indirect antioxidant actions. Considering the case of a metabolite resulting from the oxidation of quercetin, we offer a comprehensive description of the evidence that increasingly supports the concept that, in the case of certain flavonoids, the oxidation of phenolics emerges as a mechanism that markedly amplifies their original antioxidant properties. An overlooked topic of great phytomedicine potential is thus unraveled.

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Protection of the vascular endothelium in experimental situations

Interdisciplinary Toxicology ◽

10.2478/v10102-011-0005-y ◽

2011 ◽

Vol 4 (1) ◽

pp. 20-26 ◽

Cited By ~ 16

Author(s):

Ružena Sotníková ◽

Jana Nedelčevová ◽

Jana Navarová ◽

Viera Nosáľová ◽

Katarína Drábiková ◽

...

Keyword(s):

Oxidative Stress ◽

Vascular Endothelium ◽

Vascular Dysfunction ◽

Antioxidant Properties ◽

Pharmacological Intervention ◽

Ros Production ◽

Nitric Oxide Radical ◽

Endothelium Dependent Relaxation

Protection of the vascular endothelium in experimental situationsOne of the factors proposed as mediators of vascular dysfunction observed in diabetes is the increased generation of reactive oxygen species (ROS). This provides support for the use of antioxidants as early and appropriate pharmacological intervention in the development of late diabetic complications. In streptozotocin (STZ)-induced diabetes in rats we observed endothelial dysfuction manifested by reduced endothelium-dependent response to acetylcholine of the superior mesenteric artery (SMA) and aorta, as well as by increased endothelaemia. Changes in endothelium-dependent relaxation of SMA were induced by injury of the nitric oxide radical (·NO)-signalling pathway since the endothelium-derived hyperpolarising factor (EDHF)-component of relaxation was not impaired by diabetes. The endothelial dysfunction was accompanied by decreased ·NO bioavailabity as a consequence of reduced activity of eNOS rather than its reduced expression. The results obtained using the chemiluminiscence method (CL) argue for increased oxidative stress and increased ROS production. The enzyme NAD(P)H-oxidase problably participates in ROS production in the later phases of diabetes. Oxidative stress was also connected with decreased levels of reduced glutathione (GSH) in the early phase of diabetes. After 10 weeks of diabetes, adaptational mechanisms probably took place because GSH levels were not changed compared to controls. Antioxidant properties of SMe1EC2 foundin vitrowere partly confirmedin vivo.Administration of SMe1EC2 protected endothelial function. It significantly decreased endothelaemia of diabetic rats and improved endothelium-dependent relaxation of arteries, slightly decreased ROS-production and increased bioavailability of ·NO in the aorta. Further studies with higher doses of SMe1EC2 may clarify the mechanism of its endothelium-protective effectin vivo.

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In Vitro Study of Antioxidant Activity of Serum and Plasma Samples As Well As Glutathione Exposed to Various Exogenous Stress Factors

10.21203/rs.3.rs-630921/v1 ◽

2021 ◽

Author(s):

Małgorzata Olszowy-Tomczyk ◽

Łukasz Paprotny ◽

Agnieszka Celejewska ◽

Dorota Szewczak ◽

Dorota Wianowska

Keyword(s):

Oxidative Stress ◽

Antioxidant Activity ◽

Antioxidant Properties ◽

In Vitro Study ◽

Stress Factors ◽

Plasma Samples ◽

Serum Samples ◽

Exogenous Stress

Abstract The imbalance between the production of Reactive Oxygen Species (ROS) and their sequestration promotes the formation of so-called oxidative stress conditions which are considered crucial in the aging process and development of many human diseases. Glutathione plays an essential role in the antioxidative barricade against ROS. Its role in the detoxification process of xenobiotics and carcinogen is also known. However, there are no comparative studies on the antioxidant properties of both biological samples and glutathione as well as the change in these properties as a result of exposure to various stress factors. This paper fills this gap comparing the antioxidant activity of serum and plasma samples of the known glutathione content with the activity of glutathione itself assessed by the different methods. In addition, it reveals a significant role of environmental xenobiotics in oxidative stress and differentiates the stress induced by different groups of drugs, among which the greatest one has been demonstrated for antiarrhythmic drugs and cytostatics. More importantly, it proves that human plasma is more resistant to stress factors and N-acetylcysteine clearly promotes the extension of antioxidant properties of both the plasma and serum samples. The latter conclusion is consistent with the implied preventive and/or supportive action of this drug against SARS-CoV-2.

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Rhizophora Mucronata Lam. (Mangrove) Bark Extract Prevents Ethanol-induced Liver Injury, Oxidative Stress and Apoptosis in Swiss Albino Mice

10.21203/rs.3.rs-1132624/v1 ◽

2021 ◽

Author(s):

Chitra Jairaman ◽

Sabine Matou-Nasri ◽

Zeyad I Alehaideb ◽

Syed Ali Mohamed Yacoob ◽

Anuradha Venkataraman ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Histopathological Examination ◽

Bark Extract ◽

High Dose ◽

Protective Effects ◽

Rhizophora Mucronata ◽

Ethanol Intoxication ◽

Hepatoprotective Effects

Abstract The bark extract of Rhizophora mucronata (BERM) was recently reported for its prominent in vitro protective effects against liver cell line toxicity caused by various toxicants, including ethanol. Here, we aimed to verify the in vivo hepatoprotective effects of BERM against ethanol intoxication. An oral administration of different concentrations (100, 200, and 400 mg/kg) of BERM prior to high-dose ethanol via intraperitoneal injection was performed in mice. On the 7th day, liver and kidney sections were dissected out for histopathological examination. The ethanol intoxication caused large areas of liver necrosis while the kidneys were not affected. Pre-BERM administration decreased ethanol-induced liver injury, as compared to the mice treated with ethanol alone. In addition, the pre-BERM administration resulted in a decrement in the level of ethanol-induced oxidative stress, revealed by a concomitant increase of GSH and a decrease of MDA hepatic levels. The BERM extract also reversed the ethanol-induced liver injury and hepatotoxicity, characterized by the low detection of TNF-α gene expression level and fragmented DNA, respectively. Altogether, BERM extract exerts antioxidative activities and present promising hepatoprotective effects against ethanol intoxication. The identification of the related bioactive compounds will be of interest for future use at physiological concentrations in ethanol-intoxicated individuals.

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Formulation of Nanomicelles to Improve the Solubility and the Oral Absorption of Silymarin

Molecules ◽

10.3390/molecules24091688 ◽

2019 ◽

Vol 24 (9) ◽

pp. 1688 ◽

Cited By ~ 16

Author(s):

Vieri Piazzini ◽

Mario D’Ambrosio ◽

Cristina Luceri ◽

Lorenzo Cinci ◽

Elisa Landucci ◽

...

Keyword(s):

Encapsulation Efficiency ◽

Oral Absorption ◽

Drug Loading ◽

Antioxidant Properties ◽

Aqueous Solubility ◽

Average Diameter ◽

Critical Micellar Concentration ◽

Polydispersity Index ◽

Vitamin E Tpgs

Two novel nanomicellar formulations were developed to improve the poor aqueous solubility and the oral absorption of silymarin. Polymeric nanomicelles made of Soluplus and mixed nanomicelles combining Soluplus with d-α-tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS) were prepared using the thin film method. Physicochemical parameters were investigated, in particular the average diameter, the homogeneity (expressed as polydispersity index), the zeta potential, the morphology, the encapsulation efficiency, the drug loading, the critical micellar concentration and the cloud point. The sizes of ~60 nm, the narrow size distribution (polydispersity index ≤0.1) and the encapsulation efficiency >92% indicated the high affinity between silymarin and the core of the nanomicelles. Solubility studies demonstrated that the solubility of silymarin increased by ~6-fold when loaded into nanomicelles. Furthermore, the physical and chemical parameters of SLM-loaded formulations stored at room temperature and in refrigerated conditions (4 °C) were monitored over three months. In vitro stability and release studies in media miming the physiological conditions were also performed. In addition, both formulations did not alter the antioxidant properties of silymarin as evidenced by the 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH) assay. The potential of the nanomicelles to increase the intestinal absorption of silymarin was firstly investigated by the parallel artificial membrane permeability assay. Subsequently, transport studies employing Caco-2 cell line demonstrated that mixed nanomicelles statistically enhanced the permeability of silymarin compared to polymeric nanomicelles and unformulated extract. Finally, the uptake studies indicated that both nanomicellar formulations entered into Caco-2 cells via energy-dependent mechanisms.

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An Antioxidant Phytotherapy to Rescue Neuronal Oxidative Stress

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nen053 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Zhihong Lin ◽

Danni Zhu ◽

Yongqing Yan ◽

Boyang Yu ◽

Qiujuan Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Aqueous Extract ◽

Ischemia Reperfusion ◽

Brain Infarction ◽

Reaction System ◽

Artery Occlusion ◽

Dependent Manner ◽

Endogenous Antioxidant

Oxidative stress is involved in the pathogenesis of ischemic neuronal injury. A Chinese herbal formula composed ofPoria cocos(Chinese name:Fu Ling),Atractylodes macrocephala(Chinese name:Bai Zhu) andAngelica sinensis(Chinese names:Danggui, Dong quai, Donggui; Korean name:Danggwi) (FBD), has been proved to be beneficial in the treatment of cerebral ischemia/reperfusion (I/R).This study was carried out to evaluate the protective effect of FBD against neuronal oxidative stressin vivoandin vitro. Rat I/R were established by middle cerebral artery occlusion (MCAO) for 1 h, followed by 24 h reperfusion. MCAO led to significant depletion in superoxide dismutase and glutathione and rise in lipid peroxidation (LPO) and nitric oxide in brain. The neurological deficit and brain infarction were also significantly elevated by MCAO as compared with sham-operated group. All the brain oxidative stress and damage were significantly attenuated by 7 days pretreatment with the aqueous extract of FBD (250 mg kg−1, p.o.). Moreover, cerebrospinal fluid sampled from FBD-pretreated rats protected PC12 cells against oxidative insult induced by 0.2 mM hydrogen peroxide, in a concentration and time-dependent manner (IC5010.6%, ET501.2 h). However, aqueous extract of FBD just slightly scavenged superoxide anion radical generated in xanthine–xanthine oxidase system (IC502.4 mg ml−1) and hydroxyl radical generated in Fenton reaction system (IC503.6 mg ml−1). In conclusion, FBD was a distinct antioxidant phytotherapy to rescue neuronal oxidative stress, through blocking LPO, restoring endogenous antioxidant system, but not scavenging free radicals.

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