scholarly journals Kai-Xin-San Attenuates Doxorubicin-Induced Cognitive Impairment by Reducing Inflammation, Oxidative Stress, and Neural Degeneration in 4T1 Breast Cancer Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Wenjiao Lyu ◽  
Mingzi Ouyang ◽  
Xiaomeng Ma ◽  
Tiantian Han ◽  
Dajin Pi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Survival Time ◽  
Inflammatory Cytokines ◽  
Calcium Binding ◽  
Neural Degeneration ◽  
Study Results ◽  
Morris Water Maze Task ◽  
4T1 Breast Cancer

Objective. This study explored the potential therapeutic effect and possible mechanism of Kai-Xin-San (KXS) on doxorubicin-induced cognitive impairment in 4T1 breast cancer mice. Methods. A model of chemotherapy-induced cognitive impairment (CICI) was established with the injection of doxorubicin (DOX, 5 mg/kg) at a 7-day interval in a 4T1 breast cancer mouse. KXS was given (1 g/kg) daily by gavage over three weeks starting at the first week while giving DOX. The Morris water maze task was performed to measure the CICI-like behaviors. Oxidative stress markers in the hippocampus, inflammatory cytokines in the serum and hippocampus, Nissl staining, immunofluorescence staining, and analysis for Glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 of the hippocampus were examined to explore the effect and mechanism of KXS on DOX-induced CICI. Meanwhile, tumor growth and survival time were tested in this study. Results. CICI-like behaviors induced by DOX occurred earlier and were severer than the cognitive impairment induced by the tumor, and the effect of KXS on improving the cognitive impairment was obvious. KXS protected against DOX-induced neuroinflammation by decreasing levels of proinflammatory cytokines interleukin-6, interleukin-12p70, and tumor necrosis factor-alpha in both serum and brain and interleukin-1β in the brain, increasing the anti-inflammatory cytokines interleukin-4 in the serum and interleukin-10 in the hippocampus, and inhibiting the astrocytic hyperplasia and microglial polarization in the hippocampus. KXS reduced neural degeneration and protected against DOX-induced oxidative stress according to decreased malondialdehyde level, increased glutathione level, and enhanced activities of superoxide dismutase, catalase, and glutathione peroxidase. Moreover, KXS recovered the lost body weights after DOX administration and prolonged the survival times of mice. Conclusions. KXS may attenuate DOX-induced cognitive impairment by regulating inflammatory responses and reducing oxidative stress and neural degeneration. These findings also presented the role of KXS in improving the quality of life and prolonging survival time in breast cancer mice that received chemotherapy.

scholarly journals Hyaluronic Acid Improves Hydrogen Peroxide Modulatory Effects on Calcium Channel and Sodium-Potassium Pump in 4T1 Breast Cancer Cell Line

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ardeshir Abbasi ◽  
Nafiseh Pakravan ◽  
Zuhair Mohammad Hassan
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Hyaluronic Acid ◽  
Cancer Cells ◽  
Breast Cancer Cell Line ◽  
Cancer Cell Line ◽  
Sodium Potassium ◽  
Normal Cells ◽  
4T1 Breast Cancer ◽  
Sodium And Potassium

Maintaining homeostasis of ion concentrations is critical in cancer cells. Under hypoxia, the levels of channels and pumps in cancer cells are more active than normal cells suggesting ion channels as a suitable therapeutic target. One of the contemporary ways for cancer therapy is oxidative stress. However, the effective concentration of oxidative stress on tumor cells has been reported to be toxic for normal cells as well. In this study, we benefited from the modifying effects of hyaluronic acid (HA) on H2O2, as a free radical source, to make a gradual release of oxidative stress on cancer cells while preventing/decreasing damage to normal cells under normoxia and hypoxic conditions. To do so, we initially investigated the optimal concentration of HA antioxidant capacity by the DPPH test. In the next step, we found optimum H2O2 dose by treating the 4T1 breast cancer cell line with increasing concentrations (0, 10, 20, 50,100, 200, 500, and 1000 μM) of H2O2 alone or H2O2 + HA (83%) for 24 hrs. The calcium channel and the sodium-potassium pumps were then evaluated by measuring the levels of calcium, sodium, and potassium ions using an atomic absorption flame spectrophotometer. The results revealed that treatment with H2O2 or H2O2+ HA led to an intracellular increase of calcium, sodium, and potassium in the normoxic and hypoxic circumstances in a dose-dependent manner. It is noteworthy that H2O2 + HA treatment had more favorable and controllable effects compared with H2O2 alone. Moreover, HA optimizes the antitumor effect of oxidative stress exerted by H2O2 making H2O2 + HA suitable for clinical use in cancer treatment along with chemotherapy.

scholarly journals L-Carnitine Enhances Axonal Plasticity and Improves White-Matter Lesions after Chronic Hypoperfusion in Rat Brain

2015 ◽  
Vol 35 (3) ◽  
pp. 382-391 ◽  
Author(s):  
Yuji Ueno ◽  
Masato Koike ◽  
Yoshiaki Shimada ◽  
Hideki Shimura ◽  
Kenichiro Hira ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
White Matter ◽  
Oxidative Dna Damage ◽  
White Matter Lesions ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Axonal Plasticity ◽  
Morris Water Maze Task ◽  
Phosphorylated Akt

Chronic cerebral hypoperfusion causes white-matter lesions (WMLs) with oxidative stress and cognitive impairment. However, the biologic mechanisms that regulate axonal plasticity under chronic cerebral hypoperfusion have not been fully investigated. Here, we investigated whether L-carnitine, an antioxidant agent, enhances axonal plasticity and oligodendrocyte expression, and explored the signaling pathways that mediate axonal plasticity in a rat chronic hypoperfusion model. Adult male Wistar rats subjected to ligation of the bilateral common carotid arteries (LBCCA) were treated with or without L-carnitine. L-carnitine-treated rats exhibited significantly reduced escape latency in the Morris water maze task at 28 days after chronic hypoperfusion. Western blot analysis indicated that L-carnitine increased levels of phosphorylated high-molecular weight neurofilament (pNFH), concurrent with a reduction in phosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN), and increased phosphorylated Akt and mammalian target of rapamycin (mTOR) at 28 days after chronic hypoperfusion. L-carnitine reduced lipid peroxidation and oxidative DNA damage, and enhanced oligodendrocyte marker expression and myelin sheath thickness after chronic hypoperfusion. L-carnitine regulates the PTEN/Akt/mTOR signaling pathway, and enhances axonal plasticity while concurrently ameliorating oxidative stress and increasing oligodendrocyte myelination of axons, thereby improving WMLs and cognitive impairment in a rat chronic hypoperfusion model.

scholarly journals Doxorubicin-Induced Cognitive Impairment: The Mechanistic Insights

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiajia Du ◽  
Aoxue Zhang ◽  
Jing Li ◽  
Xin Liu ◽  
Shuai Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Dna Damage ◽  
Cognitive Impairment ◽  
Adjuvant Chemotherapy ◽  
Cognitive Deficits ◽  
Attention And Memory ◽  
Epigenetic Factors ◽  
Glial Cell Interactions ◽  
Chemo Brain

Chemotherapy can significantly prolong the survival of patients with breast cancer; Nevertheless, the majority of patients receiving chemotherapy such as doxorubicin may have cognitive deficits that manifest as impairments in learning, reasoning, attention, and memory. The phenomenon of chemotherapy-induced cognitive decline is termed as chemotherapy-related cognitive impairment (CRCI) or chemo-brain. Doxorubicin (DOX), a commonly used drug in adjuvant chemotherapy for patients with breast cancer, has been reported to induce chemo-brain through a variety of mechanisms including DNA damage, oxidative stress, inflammation, dysregulation of apoptosis and autophagy, changes in neurotransmitter levels, mitochondrial dysfunction, glial cell interactions, neurogenesis inhibition, and epigenetic factors. These mechanisms do not operate independently but are inter-related, coordinately contributing to the development of chemo-brain. Here we review the relationships of these mechanisms and pathways in attempt to provide mechanistic insights into the doxorubicin-induced cognitive impairment.

Metabolomics and Pharmacological Screening of Aspergillus versicolor Isolated from Hyrtios erectus Red Sea Sponge; Egypt

2020 ◽  
Vol 16 (7) ◽  
pp. 1083-1102
Author(s):  
Mohamed A. Shreadah ◽  
Nehad M.A. El Moneam ◽  
Samy A. El-Assar ◽  
Asmaa Nabil-Adam
Keyword(s):  
Oxidative Stress ◽  
Red Sea ◽  
Crude Extract ◽  
Quantitative Methods ◽  
Total Phenolic ◽  
Aspergillus Versicolor ◽  
Crude Extracts ◽  
Study Results ◽  
Anti Inflammatory ◽  
Pharmacological Screening

Background: Aspergillus Versicolor is a marine-derived fungus isolated from Hyrtios Erectus Red Sea sponge. Methods: The aim of this study was to carry out a pharmacological screening and investigation for the in vitro biological activity (antioxidant, cholinergic, antidiabetic and anticancer) of Aspergillus Versicolor crude extract’s active compounds by using different qualitative and quantitative methods. Results: The present study results showed that Aspergillus Versicolor crude extracts contain 0.6 mg total phenolic/mg crude extract. Aspergillus Versicolor also showed a potent antioxidative capacity by decreasing the oxidation of ABTS. The anticancer and inhibitory effects of Aspergillus Versicolor crude extracts on PTK and SHKI were found to be 75.29 % and 80.76%; respectively. The AChE inhibitory assay revealed that Aspergillus Versicolor extracts had an inhibitory percentage of 86.67%. Furthermore, the anti-inflammatory activity using COX1, COX2, TNF, and IL6 was 77.32, 85.21 %, 59.83%, and 56.15%; respectively. Additionally, the anti-viral effect using reverse transcriptase enzyme showed high antiviral activity with 92.10 %. Conclusion: The current study confirmed that the Aspergillus versicolor crude extract and its active constituents showed strong effects on diminishing the oxidative stress, neurodegenerative damage, antiinflammatory, anti-cancer and anti-viral, suggesting their beneficial role as a promising fermented product in the treatment of cancer, oxidative stress, Alzheimer's, anti-inflammatory and anti-viral diseases.

Apoptotic Effects of Melittin on 4T1 Breast Cancer Cell Line is associated with Up Regulation of Mfn1 and Drp1 mRNA Expression

2020 ◽  
Vol 20 (7) ◽  
pp. 790-799 ◽  
Author(s):  
Farnaz D. Moghaddam ◽  
Pejman Mortazavi ◽  
Somayeh Hamedi ◽  
Mohammad Nabiuni ◽  
Nasim H. Roodbari
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Hemolytic Activity ◽  
Breast Cancer Cells ◽  
Flow Cytometric Analysis ◽  
Control Group ◽  
Flow Cytometric ◽  
4T1 Cells ◽  
4T1 Breast Cancer ◽  
Apoptotic Effects

Background and Purpose: Melittin, as the main ingredient of honeybee venom, that has shown anticancer properties. The present study aimed at investigating the cytotoxic impacts of melittin on 4T1 breast cancer cells. Methods: Hemolytic activity of different concentrations (0.125, 0.25, 0.5, 1, 2, 4, 8μg/ml) of melittin was assayed and then cytotoxicity of selected concentrations of melittin (2, 4, 8, 16, 32, and 64μg/ml), 2 and 4μg/ml of cisplatin and 0.513, 0.295 and 0.123μg/ml of doxorubicin was evaluated on 4T1 cells using MTT assay. We used Morphological evaluation and flow cytometric analysis was used. Real time PCR was also used to determine mRNA expression of Mfn1 and Drp1 genes. Results: All compounds showed anti-proliferative effects on the tumor cell line with different potencies. Melittin had higher cytotoxicity against 4T1 breast cancer cells (IC50= 32μg/ml-72h) and higher hemolytic activity (HD50= 1μg/ml), as compared to cisplatin and doxorubicin. Mellitin at 16 and 32μg/ml showed apoptotic effects on 4T1 cells according to the flow cytometric analysis. The Real time PCR analysis of Drp1 and Mfn1 expression in cells treated with 16μg/ml of melittin revealed an up-regulation in Drp1 and Mfn1 genes mRNA expression in comparison with control group. Treatment with 32μg/ml of melittin was also associated with a rise in mRNA expression of Drp1 and Mfn1 as compared to the control group. Conclusion: The results of this study showed that melittin has anticancer effects on 4T1 cell lines in a dose and time dependent manner and can be a good candidate for further research on breast cancer treatment.

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