Protection against Doxorubicin-Induced Cytotoxicity by Geniposide Involves AMPKα Signaling Pathway

Oxidative stress and cardiomyocyte apoptosis play critical roles in the development of doxorubicin- (DOX-) induced cardiotoxicity. Our previous study found that geniposide (GE) could inhibit cardiac oxidative stress and apoptosis of cardiomyocytes but its role in DOX-induced heart injury remains unknown. Our study is aimed at investigating whether GE could protect against DOX-induced heart injury. The mice were subjected to a single intraperitoneal injection of DOX (15 mg/kg) to induce cardiomyopathy model. To explore the protective effects, GE was orally given for 10 days. The morphological examination and biochemical analysis were used to evaluate the effects of GE. H9C2 cells were used to verify the protective role of GE in vitro. GE treatment alleviated heart dysfunction and attenuated cardiac oxidative stress and cell loss induced by DOX in vivo and in vitro. GE could activate AMP-activated protein kinase α (AMPKα) in vivo and in vitro. Moreover, inhibition of AMPKα could abolish the protective effects of GE against DOX-induced oxidative stress and apoptosis. GE could protect against DOX-induced heart injury via activation of AMPKα. GE has therapeutic potential for the treatment of DOX cardiotoxicity.

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Tetrahydrocurcumin Ameliorates Diabetic Cardiomyopathy by Attenuating High Glucose-Induced Oxidative Stress and Fibrosis via Activating the SIRT1 Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6746907 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 12

Author(s):

Kaifeng Li ◽

Mengen Zhai ◽

Liqing Jiang ◽

Fan Song ◽

Bin Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Diabetic Cardiomyopathy ◽

High Glucose ◽

Therapeutic Potential ◽

Ros Generation ◽

Protective Effects ◽

Collagen Iii

Hyperglycemia-induced oxidative stress and fibrosis play a crucial role in the development of diabetic cardiomyopathy (DCM). Tetrahydrocurcumin (THC), a major bioactive metabolite of natural antioxidant curcumin, is reported to exert even more effective antioxidative and superior antifibrotic properties as well as anti-inflammatory and antidiabetic abilities. This study was designed to investigate the potential protective effects of THC on experimental DCM and its underlying mechanisms, pointing to the role of high glucose-induced oxidative stress and interrelated fibrosis. In STZ-induced diabetic mice, oral administration of THC (120 mg/kg/d) for 12 weeks significantly improved the cardiac function and ameliorated myocardial fibrosis and cardiac hypertrophy, accompanied by reduced reactive oxygen species (ROS) generation. Mechanically, THC administration remarkably increased the expression of the SIRT1 signaling pathway both in vitro and in vivo, further evidenced by decreased downstream molecule Ac-SOD2 and enhanced deacetylated production SOD2, which finally strengthened antioxidative stress capacity proven by repaired activities of SOD and GSH-Px and reduced MDA production. Additionally, THC treatment accomplished its antifibrotic effect by depressing the ROS-induced TGFβ1/Smad3 signaling pathway followed by reduced expression of cardiac fibrotic markers α-SMA, collagen I, and collagen III. Collectively, these finds demonstrated the therapeutic potential of THC treatment to alleviate DCM mainly by attenuating hyperglycemia-induced oxidative stress and fibrosis via activating the SIRT1 pathway.

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Irisin alleviates obesity-related spermatogenesis dysfunction via the regulation of the AMPKα signalling pathway

Reproductive Biology and Endocrinology ◽

10.1186/s12958-021-00821-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yang Mu ◽

Huang-Guan Dai ◽

Ling-Bo Luo ◽

Jing Yang

Keyword(s):

Oxidative Stress ◽

Sperm Count ◽

Underlying Mechanism ◽

Signalling Pathway ◽

Protective Effects ◽

Exercise Induced ◽

Amp Activated Protein Kinase

Abstract Background Infertility is a common complication in obese men. Oxidative stress and testicular apoptosis play critical roles in obesity-induced spermatogenesis dysfunction. It has been reported that irisin, an exercise-induced myokine, may attenuate oxidative damage and testicular apoptosis in several diseases; however, its role in obesity-induced spermatogenesis dysfunction remains unclear. The purpose of this study was to investigate the role and underlying mechanism of irisin in obesity-induced dysfunction of spermatogenesis. Methods Male mice were fed a high-fat diet (HFD) for 24 weeks to establish a model of obesity-induced spermatogenesis dysfunction. To explore the effects of irisin, mice were subcutaneously infused with recombinant irisin for 8 weeks beginning at 16 weeks after starting a HFD. To confirm the role of AMP-activated protein kinase α (AMPKα), AMPKα-deficient mice were used. Results The data showed decreased serum irisin levels in obese patients, which was negatively correlated with sperm count and progressive motility. Irisin was downregulated in the plasma and testes of obese mice. Supplementation with irisin protected against HFD-induced spermatogenesis dysfunction and increased testosterone levels in mice. HFD-induced oxidative stress, endoplasmic reticulum (ER) stress and testicular apoptosis were largely attenuated by irisin treatment. Mechanistically, we identified that irisin activated the AMPKα signalling pathway. With AMPKα depletion, we found that the protective effects of irisin on spermatogenesis dysfunction were abolished in vivo and in vitro. Conclusions In conclusion, we found that irisin alleviated obesity-related spermatogenesis dysfunction via activation of the AMPKα signalling pathway. Based on these findings, we hypothesized that irisin is a potential therapeutic agent against obesity-related spermatogenesis dysfunction.

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Scavenging Properties of Plant-Derived Natural Biomolecule Para-Coumaric Acid in the Prevention of Oxidative Stress-Induced Diseases

Antioxidants ◽

10.3390/antiox10081205 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1205

Author(s):

Shubhadeep Roychoudhury ◽

Barnali Sinha ◽

Birupakshya Paul Choudhury ◽

Niraj Kumar Jha ◽

Partha Palit ◽

...

Keyword(s):

Oxidative Stress ◽

Therapeutic Potential ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Vascular Diseases ◽

Protective Role ◽

Coumaric Acid ◽

Inflammatory Reactions

Para-coumaric acid (p-CA) is a plant derived secondary metabolite belonging to the phenolic compounds. It is widely distributed in the plant kingdom and found mainly in fruits, vegetables, and cereals. Various in vivo and in vitro studies have revealed its scavenging and antioxidative properties in the reduction of oxidative stress and inflammatory reactions. This evidence-based review focuses on the protective role of p-CA including its therapeutic potential. p-CA and its conjugates possesses various bioactivities such as antioxidant, anti-inflammatory, anti-cancer, anti-diabetic, and anti-melanogenic properties. Due to its potent free radical scavenging activity, it can mitigate the ill effects of various diseases including arthritis, neurological disorders, and cardio-vascular diseases. Recent studies have revealed that p-CA can ameliorate the harmful effects associated with oxidative stress in the reproductive system, also by inhibiting enzymes linked with erectile function.

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Transit and Metabolic Pathways of Quercetin in Tubular Cells: Involvement of Its Antioxidant Properties in the Kidney

Antioxidants ◽

10.3390/antiox10060909 ◽

2021 ◽

Vol 10 (6) ◽

pp. 909

Author(s):

Daniel Muñoz-Reyes ◽

Ana I. Morales ◽

Marta Prieto

Keyword(s):

Oxidative Stress ◽

Therapeutic Potential ◽

Antioxidant Properties ◽

The Body ◽

Protective Effects ◽

Metabolic Processes ◽

Intracellular Space ◽

Tubular Cells

Quercetin is a flavonoid with antioxidant, antiviral, antimicrobial, and anti-inflammatory properties. Therefore, it has been postulated as a molecule with great therapeutic potential. The renoprotective capacity of quercetin against various toxins that produce oxidative stress, in both in vivo and in vitro models, has been shown. However, it is not clear whether quercetin itself or any of its metabolites are responsible for the protective effects on the kidney. Although the pharmacokinetics of quercetin have been widely studied and the complexity of its transit throughout the body is well known, the metabolic processes that occur in the kidney are less known. Because of that, the objective of this review was to delve into the molecular and cellular events triggered by quercetin and/or its metabolites in the tubular cells, which could explain some of the protective properties of this flavonoid against oxidative stress produced by toxin administration. Thus, the following are analyzed: (1) the transit of quercetin to the kidney; (2) the uptake mechanisms of quercetin and its metabolites from plasma to the tubular cells; (3) the metabolic processes triggered in those cells, which affect the accumulation of metabolites in the intracellular space; and (4) the efflux mechanisms of these compounds and their subsequent elimination through urine. Finally, it is discussed whether those processes that are mediated in the tubular cells and that give rise to different metabolites are related to the antioxidant and renoprotective properties observed after the administration of quercetin.

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Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer

Current Pharmaceutical Design ◽

10.2174/1381612825666190110145151 ◽

2019 ◽

Vol 24 (39) ◽

pp. 4626-4638 ◽

Cited By ~ 13

Author(s):

Reyhaneh Moradi-Marjaneh ◽

Seyed M. Hassanian ◽

Farzad Rahmani ◽

Seyed H. Aghaee-Bakhtiari ◽

Amir Avan ◽

...

Keyword(s):

Oxidative Stress ◽

Colorectal Cancer ◽

Therapeutic Potential ◽

Vegf Signaling ◽

Anticancer Effects ◽

Inhibition Of Angiogenesis ◽

Underlying Mechanisms ◽

Apoptotic Activity

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

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A Protective Role of Paeoniflorin in Fluctuant Hyperglycemia-Induced Vascular Endothelial Injuries through Antioxidative and Anti-Inflammatory Effects and Reduction of PKCβ1

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/5647219 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Jing-Shang Wang ◽

Ye Huang ◽

Shuping Zhang ◽

Hui-Jun Yin ◽

Lei Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Protein Level ◽

Umbilical Vein ◽

Protective Role ◽

Vascular Endothelial ◽

Glucose Levels ◽

Umbilical Vein Endothelial Cells

Hyperglycemia fluctuation is associated with diabetes mellitus (DM) complications when compared to persistent hyperglycemia. Previous studies have shown that paeoniflorin (PF), through its antiapoptosis, anti-inflammation, and antithrombotic properties, effectively protects against cardiovascular and cerebrovascular disease. However, the mechanism underlying the protection from PF against vascular injuries induced by hyperglycemia fluctuations remains poorly understood. Herein, we investigated the potential protective role of PF on human umbilical vein endothelial cells (HUVECs) subjected to intermittent glucose levels in vitro and in DM rats with fluctuating hyperglycemia in vivo. A remarkable increased apoptosis associated with elevated inflammation, increased oxidative stress, and high protein level of PKCβ1 was induced in HUVECs by intermittently changing glucose for 8 days, and PF recovered those detrimental changes. LY333531, a potent PKCβ1 inhibitor, and metformin manifested similar effects. Additionally, in DM rats with fluctuating hyperglycemia, PF protected against vascular damage as what has been observed in vitro. Taken together, PF attenuates the vascular injury induced by fluctuant hyperglycemia through oxidative stress inhibition, inflammatory reaction reduction, and PKCβ1 protein level repression, suggesting its perspective clinical usage.

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Mice pancreatic islets protection from oxidative stress induced by single-walled carbon nanotubes through naringin

Human & Experimental Toxicology ◽

10.1177/0960327118769704 ◽

2018 ◽

Vol 37 (12) ◽

pp. 1268-1281 ◽

Cited By ~ 4

Author(s):

A Ahangarpour ◽

S Alboghobeish ◽

AA Oroojan ◽

MA Dehghani

Keyword(s):

Oxidative Stress ◽

Carbon Nanotubes ◽

Insulin Secretion ◽

Pancreatic Islets ◽

Mtt Assay ◽

Antioxidant Defense System ◽

Protective Effects ◽

Cell Functions

The growing use of carbon nanotubes (CNTs) emphasizes the importance of its potential toxic effects on the human health. Previous studies proved that CNTs caused oxidative stress and decreased cell viability. On the other hand, reactive oxygen species (ROS) and oxidative stress impaired β-cell functions and reduced the insulin secretion. However, there is not any study on the effects of CNTs on islets and β-cells. Therefore, the present study aimed to evaluate the effects of single-walled CNTs (SWCNTs) on oxidative stress in islets in addition to the protective effects of naringin (NRG) as an antioxidant . We examined the effects of SWCNTs and naringin on islets by 3,4 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay; measurement of insulin secretion, ROS, and malondialdehyde (MDA); activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) peroxidase (GSH-Px); and content of GSH and mitochondrial membrane potential (MMP). The MTT assay demonstrated that decreased viability of islets cells was dose-dependent with exposure to SWCNTs. Further studies revealed that SWCNTs decreased insulin secretion and MMP, induced the formation of ROS, increased the level of MDA, and decreased the activities of SOD, GSH-Px, and CAT and content of GSH. Furthermore, the pretreatment of islets with naringin significantly reverted back these changes. These findings revealed that SWCNTs might induce the oxidative stress to pancreatic islets, causing the occurrence of diabetes, and the protective effects of naringin that was mediated by augmentation of the antioxidant defense system of islets. Our research indicated the necessity for further in vivo and in vitro researches on the effects of SWCNTs and naringin on diabetes.

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Protective effect of essential oil of Cinnamomum verum bark on hepatic and renal toxicity induced by carbon tetrachloride in rats

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2018-0246 ◽

2019 ◽

Vol 44 (6) ◽

pp. 606-618 ◽

Cited By ~ 1

Author(s):

Khaled Bellassoued ◽

Ferdaws Ghrab ◽

Houda Hamed ◽

Rim Kallel ◽

Jos van Pelt ◽

...

Keyword(s):

Oxidative Stress ◽

Essential Oil ◽

Renal Toxicity ◽

Density Lipoprotein ◽

Protein Carbonyl ◽

Untreated Group ◽

Protective Effects ◽

Glutamyl Transferase

The inner bark of cinnamon (Cinnamomum verum) is widely used as a spice. Cinnamon plants are also a valuable source of essential oil used for medicinal purposes. The present study aimed to investigate the composition and in vitro antioxidant activity of essential oil of C. verum bark (CvEO) and its protective effects in vivo on CCl4-induced hepatic and renal toxicity in rats. Groups of animals were pretreated for 7 days with CvEO (70 or 100 mg/kg body weight) or received no treatment and on day 7 a single dose of CCl4 was used to induce oxidative stress. Twenty-four hours after CCl4 administration, the animals were euthanized. In the untreated group, CCl4 induced an increase in serum biochemical parameters and triggered oxidative stress in both liver and kidneys. CvEO (100 mg/kg) caused significant reductions in CCl4-elevated levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, total cholesterol, triglycerides, low-density lipoprotein, urea, and creatinine and increased the level of high-density lipoprotein compared with the untreated group. Moreover, pretreatment with CvEO at doses of 70 and 100 mg/kg before administration of CCl4 produced significant reductions in thiobarbituric acid reactive substances and protein carbonyl levels in liver and kidney tissues compared with the untreated group. The formation of pathological hepatic and kidney lesions induced by the administration of CCl4 was strongly prevented by CvEO at a dose of 100 mg/kg. Overall, this study suggests that administration of CvEO has high potential to quench free radicals and alleviate CCl4-induced hepatorenal toxicity in rats.

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Blue laser light inhibits biofilm formation in vitro and in vivo by inducing oxidative stress

npj Biofilms and Microbiomes ◽

10.1038/s41522-019-0102-9 ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 10

Author(s):

Katia Rupel ◽

Luisa Zupin ◽

Giulia Ottaviani ◽

Iris Bertani ◽

Valentina Martinelli ◽

...

Keyword(s):

Oxidative Stress ◽

Biofilm Formation ◽

Mammalian Cells ◽

Bacterial Infections ◽

Laser Light ◽

Therapeutic Potential ◽

Blue Laser ◽

Data Set

Abstract Resolution of bacterial infections is often hampered by both resistance to conventional antibiotic therapy and hiding of bacterial cells inside biofilms, warranting the development of innovative therapeutic strategies. Here, we report the efficacy of blue laser light in eradicating Pseudomonas aeruginosa cells, grown in planktonic state, agar plates and mature biofilms, both in vitro and in vivo, with minimal toxicity to mammalian cells and tissues. Results obtained using knock-out mutants point to oxidative stress as a relevant mechanism by which blue laser light exerts its anti-microbial effect. Finally, the therapeutic potential is confirmed in a mouse model of skin wound infection. Collectively, these data set blue laser phototherapy as an innovative approach to inhibit bacterial growth and biofilm formation, and thus as a realistic treatment option for superinfected wounds.

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Piperine Alleviates Doxorubicin-Induced Cardiotoxicity via Activating PPAR-γ in Mice

PPAR Research ◽

10.1155/2019/2601408 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Jie Yan ◽

Si-Chi Xu ◽

Chun-Yan Kong ◽

Xiao-Yang Zhou ◽

Zhou-Yan Bian ◽

...

Keyword(s):

Oxidative Stress ◽

Cardiac Injury ◽

Inflammatory Factors ◽

Peroxisome Proliferator ◽

Protective Effects ◽

Peroxisome Proliferator Activated Receptor ◽

Ppar Γ ◽

Myocardial Oxidative Stress

Background. Oxidative stress, inflammation and cardiac apoptosis were closely involved in doxorubicin (DOX)-induced cardiac injury. Piperine has been reported to suppress inflammatory response and pyroptosis in macrophages. However, whether piperine could protect the mice against DOX-related cardiac injury remain unclear. This study aimed to investigate whether piperine inhibited DOX-related cardiac injury in mice. Methods. To induce DOX-related acute cardiac injury, mice in DOX group were intraperitoneally injected with a single dose of DOX (15 mg/kg). To investigate the protective effects of piperine, mice were orally treated for 3 weeks with piperine (50 mg/kg, 18:00 every day) beginning two weeks before DOX injection. Results. Piperine treatment significantly alleviated DOX-induced cardiac injury, and improved cardiac function. Piperine also reduced myocardial oxidative stress, inflammation and apoptosis in mice with DOX injection. Piperine also improved cell viability, and reduced oxidative damage and inflammatory factors in cardiomyocytes. We also found that piperine activated peroxisome proliferator-activated receptor-γ (PPAR-γ), and the protective effects of piperine were abolished by the treatment of the PPAR-γ antagonist in vivo and in vitro. Conclusions. Piperine could suppress DOX-related cardiac injury via activation of PPAR-γ in mice.

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