Protective Role of Endogenous PACAP in Inflammation-induced Retinal Degeneration

Purpose: Pituitary adenylate Cyclase-Activating Polypeptide (PACAP) is a neuroprotective peptide that has been shown to exert protective effects in different models of neurodegenerative diseases, including retinal degenerations. Data obtained from PACAP-deficient (PACAP KO) mice provide evidence that endogenous PACAP has a neuroprotective role in different pathologies. PACAP KO mice show enhanced sensitivity to different insults, such as oxidative stress, hypoxia and inflammation. The aim of the present study was to investigate the protective effects of endogenous PACAP in retinal inflammation. Methods: Endotoxin-induced eye inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS) in PACAP KO and wild-type (Wt) mice. After LPS treatment, retinas were processed for histological examination. To detect the alterations of different proteins and cytokines, immunohistochemical, western blot and cytokine array were used. We also performed dark-adapted electroretinography (ERG) to detect the functional differences. Results: The thickness of nearly all layers was significantly less in LPS-injected PACAP KO mice compared to Wt animals. Increased expression of Glial Fibrillary Acidic Protein (GFAP) was induced in Müller glial cells after LPS treatment, which was more intense in PACAP KO mice. The levels of pAkt and pGSK were decreased in PACAP KO group during inflammation. LPS treatment significantly increased cytokines (sICAM-1, JE, TIMP-1) in both treated groups, but it was more expressed in PACAP KO animals. Furthermore, ERG responses were disturbed after LPS injection in PACAP KO mice. Conclusion: Our results showed that endogenous PACAP has a protective role in LPS-caused retinal inflammation.

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The Protective Role of Brain CYP2J in Parkinson’s Disease Models

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/2917981 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Yueran Li ◽

Jinhua Wu ◽

Xuming Yu ◽

Shufang Na ◽

Ke Li ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Brain Regions ◽

Protective Role ◽

Neural Cells ◽

Endogenous Substrates ◽

6 Hydroxydopamine ◽

Myd88 Signaling ◽

Lps Treatment

CYP2J proteins are present in the neural cells of human and rodent brain regions. The aim of this study was to investigate the role of brain CYP2J in Parkinson’s disease. Rats received right unilateral injection with lipopolysaccharide (LPS) or 6-hydroxydopamine (6-OHDA) in the substantia nigra following transfection with or without the CYP2J3 expression vector. Compared with LPS-treated rats, CYP2J3 transfection significantly decreased apomorphine-induced rotation by 57.3% at day 12 and 47.0% at day 21 after LPS treatment; moreover, CYP2J3 transfection attenuated the accumulation of α-synuclein. Compared with the 6-OHDA group, the number of rotations by rats transfected with CYP2J3 decreased by 59.6% at day 12 and 43.5% at day 21 after 6-OHDA treatment. The loss of dopaminergic neurons and the inhibition of the antioxidative system induced by LPS or 6-OHDA were attenuated following CYP2J3 transfection. The TLR4-MyD88 signaling pathway was involved in the downregulation of brain CYP2J induced by LPS, and CYP2J transfection upregulated the expression of Nrf2 via the inhibition of miR-340 in U251 cells. The data suggest that increased levels of CYP2J in the brain can delay the pathological progression of PD initiated by inflammation or neurotoxins. The alteration of the metabolism of the endogenous substrates (e.g., AA) could affect the risk of neurodegenerative disease.

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Protective Role of Leptadenia Hastata on the Haematological and Biochemical Alterations in Adrenaline-Induced Hypertensive Rats

Iranian Jornal of Toxicology ◽

10.32598/ijt.14.1.25 ◽

2020 ◽

Vol 14 (1) ◽

pp. 25-32

Author(s):

Adewuyi Hassan Abdulsalam ◽

◽

Muhammad L. Hadiza ◽

Onukogu Stella Chiamaka ◽

Ibrahim Jonathan ◽

...

Keyword(s):

Elevated Serum ◽

Protective Role ◽

Protective Effects ◽

Hypertensive Rats ◽

Bioactive Constituents ◽

Once Daily ◽

Biochemical Alterations ◽

The Mean ◽

Normal Controls

Background: Leptadenia hastata (L. Hastata) is a plant used for various diseases in Nigeria. This study evaluated the protective effects of L. hastate on the haematological and biochemical alterations in adrenaline-induced hypertensive rats. Methods: Twenty-five rats were divided equally into five groups (A-E). Groups A-D were given 0.5 mg/kg adrenaline, groups A and B were treated with 100 and 200 mg/kg the extract of L. Hastata, respectively, while groups C and D were treated with 5 mg/kg amlodipine (standard control) and normal saline (untreated control), respectively. Group E were given distilled water (normal controls). The adrenaline was injected intraperitoneally while the extract was given orally once daily for seven days. Results: Treatment with 100 and 200 mg/kg of the extract significantly reduced the elevated serum albumin, ALP, ALT, AST, chloride, sodium and creatinine, cholesterol and LDL concentrations compared with the untreated hypertensive rats. The bicarbonate level, WBC and RBC counts, mean cell hemoglobin and packed cell value were higher in rats treated with the extract compared with the untreated hypertensive rats. The mean cell value, HDL, triglyceride, urea, potassium, total and direct bilirubin concentrations in experimental groups were not significantly different from those in the controls (P<0.05). Conclusion: Our results suggest that treatment of the hypertensive rats with the extract of L. Hastata protects against renal, hepatic and cardiac damages, thus it could be considered as a natural anti-hypertensive agent. Further studies are required to identify the bioactive constituents and the mechanism(s) of action.

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Hepato & nephro protective effects of naringenin-loaded tpgs polymeric nanosuspension against cisplatin-induced toxicity

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v10i4.1544 ◽

2019 ◽

Vol 10 (4) ◽

pp. 2755-2764

Author(s):

Sumathi Rajamani ◽

Gobinath Kalyanasundaram ◽

Tamizharasi Sengodan ◽

Sivakumar Thangavelu ◽

Nikhitha K Shanmukhan ◽

...

Keyword(s):

Antioxidant Activities ◽

Aqueous Solubility ◽

Protective Role ◽

Chemotherapeutic Agents ◽

Glycol Succinate ◽

High Pressure Homogenization ◽

Protective Effects ◽

Male Wistar Rats ◽

Nephroprotective Effect

Cisplatin (Cis-Diammineplatinum (II) dichloride/CIS) is one of the most potent chemotherapeutic agents widely used in treatment of various cancers. Naringenin (NAR), a natural flavonoid, protect against CIS-induced injury in rats without hampering CIS beneficial cytotoxic activity. Even though NAR exhibits therapeutic potency, clinical evolution of the molecule is embarrassed because of very less aqueous solubility which corresponds to low availability at the site of the tumor. In our former analysis, nanosuspension of naringenin (NARNS) was developed by the method of high-pressure homogenization. The study had been continued to evaluate the protective role of D-α-Tocopheryl polyethylene glycol succinate (TPGS) coated NARNS, against oxidative stress-induced hepato and nephrotoxicity in male Wistar rats upon CIS treatment. Induction of acute hepato and neprotoxicity was done by intraperitoneal injection (i.p) injection of CIS (7 mg/kg of body weight) and administration of NAR and NARNS. Administration of NARNS virtually suppressed CIS-induced and liver injury evidenced by a reduction of lipid peroxidation level, blood urea nitrogen, serum uric acid, creatinine and elevated enzymatic antioxidant activities of superoxide dismutase, catalase, and glutathione peroxidase in rats liver tissue. Histological studies substantiated the biochemical parameters. The study suggests that NARNS has strong hepato and nephroprotective effect compared to NAR.

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The Protective Role of Feruloylserotonin in LPS-Induced HaCaT Cells

Molecules ◽

10.3390/molecules24173064 ◽

2019 ◽

Vol 24 (17) ◽

pp. 3064 ◽

Cited By ~ 3

Author(s):

Yuzhu He ◽

Byung-gook Kim ◽

Hye-Eun Kim ◽

Qiaochu Sun ◽

Shuhan Shi ◽

...

Keyword(s):

Antioxidant Activities ◽

Protective Role ◽

Related Factor ◽

Nuclear Factor ◽

Hacat Cells ◽

Protective Effects ◽

Hydroxycinnamic Acid Amides ◽

Anti Inflammatory ◽

Underlying Mechanisms

Epidermal inflammation is caused by various bacterial infectious diseases that impair the skin health. Feruloylserotonin (FS) belongs to the hydroxycinnamic acid amides of serotonin, which mainly exists in safflower seeds and has been proven to have anti-inflammatory and antioxidant activities. Human epidermis mainly comprises keratinocytes whose inflammation causes skin problems. This study investigated the protective effects of FS on the keratinocyte with lipopolysaccharides (LPS)-induced human HaCaT cells and elucidated its underlying mechanisms of action. The mechanism was investigated by analyzing cell viability, PGE2 levels, cell apoptosis, nuclear factor erythroid 2-related factor 2 (Nrf2) translocation, and TLR4/NF-κB pathway. The anti-inflammatory effects of FS were assessed by inhibiting the inflammation via down-regulating the TLR4/NF-κB pathway. Additionally, FS promoted Nrf2 translocation to the nucleus, indicating that FS showed anti-oxidative activities. Furthermore, the antioxidative and anti-inflammatory effects of FS were found to benefit each other, but were independent. Thus, FS can be used as a component to manage epidermal inflammation due to its anti-inflammatory and anti-oxidative properties.

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Crocin Improves Insulin Sensitivity and Ameliorates Adiposity by Regulating AMPK-CDK5-PPARγ Signaling

BioMed Research International ◽

10.1155/2020/9136282 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Kai Fang ◽

Ming Gu

Keyword(s):

Protein Level ◽

Biological Activities ◽

Protective Effects ◽

Metabolic Dysfunction ◽

Ampk Activation ◽

Diabetic Mice ◽

Wild Type ◽

Ampk Signaling ◽

Beneficial Effects

Crocin is a carotenoid compound which possesses multiple biological activities. Our and other laboratory’s previous findings show that crocin alleviates obesity and type 2 diabetes-related complications. We have found that crocin activates AMP-activated protein kinase (AMPK) signaling and inhibition of AMPK suppresses crocin-induced protective effects. However, the causal role of AMPK activation in the biological role of crocin is still not verified. In the present study, we showed that crocin markedly inhibits the changes of glucose metabolic parameters and serum lipid profiles in wild type diabetic mice. In AMPKα KO diabetic mice, those protective effects of crocin against glucose and lipid metabolic dysfunction were abolished. These results demonstrated AMPK activation was responsible for the beneficial effects of crocin on metabolic dysfunction. Moreover, we have shown that the antiobese effect of crocin has been abolished by the deficiency of AMPKα. We also showed that crocin induced a significant decrease of CDK5 protein level in wild type diabetic mice, while this effect was abolished in AMPKα KO diabetic mice. The regulation of downstream targets of CDK5/PPARγ by crocin was abolished by the deficiency of AMPK. In conclusion, our study verified that activation of AMPK is involved in crocin-induced protective effects against glucose and lipid metabolic dysfunction. Activation of AMPK downregulates the protein level of CDK5, followed by the decrease of PPARγ phosphorylation, leading to the inhibition of adipose formation and metabolic dysfunction. Our study provides new insights into the mechanism of protective effects of crocin and interaction of AMPK and CDK5/PPARγ signaling.

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Susceptibility to Entamoeba histolytica intestinal infection is related to reduction in natural killer T-lymphocytes in C57BL/6 mice

Infectious Disease Reports ◽

10.4081/idr.2012.e27 ◽

2012 ◽

Vol 4 (1) ◽

pp. 27 ◽

Cited By ~ 3

Author(s):

Fabrício M.S. Oliveira ◽

Bernardo C. Horta ◽

Luana O. Prata ◽

Andrezza F. Santiago ◽

Andréa C. Alves ◽

...

Keyword(s):

T Lymphocytes ◽

Natural Killer ◽

Entamoeba Histolytica ◽

Protective Role ◽

Amoebic Liver Abscess ◽

Wild Type ◽

Quantitative Analyses ◽

Cd1 Mice ◽

Natural Killer T

Entamoeba histolytica is a protozoan that causes amoebiasis. Recent studies demonstrated that natural killer T lymphocytes (NKT) are critical for preventing the development of amoebic liver abscess. In spite of that, there are only a handful of studies in the area. Herein, we explored the role of NKT cells in E. histolytica infection using C57BL/6 wild-type and CD1-/- mice. Animals were inoculated with E. histolytica and sacrificed 48 hours later to collect caecum samples that were used for quantitative analyses of lesions, trophozoites, NK1.1+ T lymphocytes and expression of the mucus protein MUC-2 by immunohistochemistry technique. Quantitative analyses confirmed that the frequency of NK1.1+ T cells was significantly lower in samples from C57BL/6 CD1-/- mice as compared to their wild type (WT) counterparts. The extension of necrotic mucosa was larger and the number of trophozoites higher in Entamoeba (Eh)-infected CD1-/- mice when compared with Eh-infected WT mice. In mice from both groups, noninfected (CTRL) and Eh-infected CD1-/-, there was a reduction in the thickness of the caecal mucosa and in the MUC-2-stained area in comparison with CTRL- and Eh-WT mice. Our results showed that NKT lymphocytes contribute to resistance against Entamoeba histolytica infection and to the control of inflammation in the colitis induced by infection. The presence of a normal epithelial layer containing appropriate levels of mucus had also a protective role against infection.

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Sildenafil (Viagra) Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model

Mediators of Inflammation ◽

10.1155/2013/321460 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 32

Author(s):

Catarina Raposo ◽

Ana Karolina de Santana Nunes ◽

Rayana Leal de Almeida Luna ◽

Shyrlene Meiry da Rocha Araújo ◽

Maria Alice da Cruz-Höfling ◽

...

Keyword(s):

Neuroprotective Effect ◽

Underlying Mechanism ◽

Protective Effects ◽

Wild Type ◽

Glutathione S Transferase ◽

Cox 2 ◽

Inflammatory Regulation ◽

Inos Inhibition ◽

Inflammatory Effect

We recently demonstrated that sildenafil reduces the expression of cytokines, COX-2, and GFAP in a demyelinating model induced in wild-type (WT) mice. Herein, the understandings of the neuroprotective effect of sildenafil and the mediation of iNOS/NO system on inflammatory demyelination induced by cuprizone were investigated. The cerebella of iNOS−/−mice were examined after four weeks of treatment with cuprizone alone or combined with sildenafil. Cuprizone increased GFAP, Iba-1, TNF-α, COX-2, IL-1β, and IFN-γexpression, decreased expression of glutathione S-transferase pi (GSTpi), and damaged myelin in iNOS−/−mice. Sildenafil reduced Iba-1, IFN-γ, and IL-1βlevels but had no effect on the expression of GFAP, TNF-α, and COX-2 compared to the cuprizone group. Sildenafil elevated GSTpi levels and improved the myelin structure/ultrastructure. iNOS−/−mice suffered from severe inflammation following treatment with cuprizone, while WT mice had milder inflammation, as found in the previous study. It is possible that inflammatory regulation through iNOS-feedback is absent in iNOS−/−mice, making them more susceptible to inflammation. Sildenafil has at least a partial anti-inflammatory effect through iNOS inhibition, as its effect on iNOS−/−mice was limited. Further studies are required to explain the underlying mechanism of the sildenafil effects.

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miR-135b Plays a Neuroprotective Role by Targeting GSK3β in MPP+-Intoxicated SH-SY5Y Cells

Disease Markers ◽

10.1155/2017/5806146 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Jianlei Zhang ◽

Wei Liu ◽

Yabo Wang ◽

Shengnan Zhao ◽

Na Chang

Keyword(s):

Cell Proliferation ◽

Glycogen Synthase ◽

Underlying Mechanism ◽

Protective Role ◽

Luciferase Reporter ◽

Dependent Manner ◽

Protective Effects ◽

Inflammatory Cytokine Production ◽

Protein Levels

miR-135a-5p was reported to play a crucial role in the protective effects of hydrogen sulfide against Parkinson’s disease (PD) by targeting rho-associated protein kinase 2 (ROCK2). However, the role of another member of miR-135 family (miR-135b) and the underlying mechanism in PD are still unclear. qRT-PCR and western blot showed that miR-135 was downregulated and glycogen synthase kinase 3β (GSK3β) was upregulated at mRNA and protein levels in MPP+-intoxicated SH-SY5Y cells in a dose- and time-dependent manner. MTT, TUNEL, and ELISA assays revealed that miR-135b overexpression significantly promoted cell proliferation and inhibited apoptosis and production of TNF-α and IL-1β in SH-SY5Y cells in the presence of MPP+. Luciferase reporter assay demonstrated that GSK3β was a direct target of miR-135b. Moreover, sodium nitroprusside (SNP), a GSK3β activator, dramatically reversed the effects of miR-135b upregulation on cell proliferation, apoptosis, and inflammatory cytokine production in MPP+-intoxicated SH-SY5Y cells. Taken together, miR-135b exerts a protective role via promotion of proliferation and suppression of apoptosis and neuroinflammation by targeting GSK3β in MPP+-intoxicated SH-SY5Y cells, providing a potential therapeutic target for the treatment of PD.

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A Contemporary View of Natriuretic Peptides in the SARS-CoV-2 Era

Frontiers in Physiology ◽

10.3389/fphys.2021.643721 ◽

2021 ◽

Vol 12 ◽

Author(s):

Speranza Rubattu ◽

Giovanna Gallo ◽

Massimo Volpe

Keyword(s):

Viral Infection ◽

Natriuretic Peptides ◽

Pulmonary Inflammation ◽

Protective Role ◽

Protective Effects ◽

Cardiac Damage ◽

Protective Function ◽

Therapeutic Benefits ◽

Prognostic Implications

The heart releases natriuretic peptides (NPs) which represent an important hormonal axis with cardiorenal protective effects. In view of their properties, NPs have pathophysiologic, diagnostic and prognostic implications in several cardiovascular diseases (CVDs). Severe pulmonary inflammation, as induced by the SARS-COV2, may increase pulmonary pressure with potential influence on NPs release, whereby normal cardiovascular integrity becomes impaired. Moreover, pre-existing CVDs are strong negative prognostic factors since they exacerbate the effects of the viral infection and lead to worse outcomes. In this context, it may be expected that NPs exert a key protective role toward the virus infection whereas an impairment of NPs release contributes to the virus deleterious effects. In this review article we explore the potential involvement of NPs in the COVID-19 disease. To this aim, we will first focus on the interactions between NPs and the Ang II/ATIR arm of the renin-angiotensin-aldosterone system (RAAS) as well as with the protective ACE2/Ang (1-7) arm of the RAAS. Subsequently, we will review evidence that strongly supports the role of increased NT-proBNP level as a marker of cardiac damage and of worse prognosis in the COVID-19 affected patients. Finally, we will discuss the potential therapeutic benefits of these protective hormones toward the viral infection through their endothelial protective function, anti-inflammatory and anti-thrombotic effects. In conclusion, the potential implications of NPs in the SARS-CoV-2 infection, as discussed in our article, represent an important issue that deserves to be fully investigated.

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The protective role of propolis against multi heavy metals-induced oxidative stress-hepato-renal damage in the male of albino rats

10.21203/rs.3.rs-422622/v1 ◽

2021 ◽

Author(s):

Ayman Ahmed Bassiouny El-Amawy ◽

Samir Attia Mohammed Zaahkouk ◽

Hesham Gamal Abdel Rasheed ◽

Bassem Elsayed Elaraby Mohammed

Keyword(s):

Heavy Metals ◽

Oral Administration ◽

Antioxidant Defense System ◽

Protective Role ◽

Albino Rats ◽

Protective Effects ◽

Toxic Heavy Metals ◽

Propolis Extract ◽

Liver And Kidney

Abstract The study was designed to clarify the hepato-renal protective effects of propolis extract against heavy metals-induced toxicity via oral administration to the males of albino rats. Lead (Pb), Nickel (Ni), Cadmium (Cd), and Antimony (Sb) are toxic heavy metals have the ability to produce reactive radicals in the biological systems causing public and animals health hazards through disrupting balances between pro-oxidant and antioxidant defense system, resulting in excessive reactive oxygen species (ROS) production. The most commonly affected organs are liver and kidney. Propolis is a natural product with different shapes and resinous substance collected by honey bees, it attenuates many diseases damage due to its anti-oxidative action and its potentiality to minimize the deleterious effects of free radicals on tissues. The concentrations of Pb, Cd, Ni and Sb as well as the activities of antioxidants endogenous enzymes including; glutathione peroxidase (Gpx), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD) were all determined in the tissues of liver and kidney; while aspartate transaminase (ASAT), alanine transaminase (ALAT), total protein (TP), urea and createnine, were measured in the serum of experimental rats beside histopathologicl examination in the tissues of liver and kidney. The oral administration of propolis provided a significantly therapeutic role against multi-metals-induced hepato-renal toxicity with relative improving to histopathological changes because of its scavenging and chelating properties as concluded from the present investigation.

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