Hexagonal boron nitride nanoparticles trigger oxidative stress by modulating thiol/disulfide homeostasis

2021 ◽  
pp. 096032712110028
Author(s):  
F Kar ◽  
İ Söğüt ◽  
C Hacıoğlu ◽  
Y Göncü ◽  
H Şenturk ◽  
...  

Background: Hexagonal boron nitride nanoparticles (hBN NPs) are encouraging nanomaterials with unique chemical properties in medicine and biomedical fields. Until now, the optimal hBN NP’s dosage and biochemical mechanism that can be used for in vivo systems has not been fully revealed. The main aim of this article is to reveal characteristics, serum and tissue interactions and any acute cytotoxic effect of different dose of hBN NPs for the first time. Methods: hBN NPs at concentrations varying between 50–3200 µg/kg was administered by intravenous injection to Wistar albino rats (n = 80) divided into seven dosage and control groups. Blood and tissue samples were taken after 24 hours. Results: Our findings suggested that higher doses hBN NPs caused oxidative stress on the serum of rats dose-dependently. However, hBN NPs did not affect thiol/disulfide homeostasis on kidney, liver, spleen, pancreas and heart tissue of rats. Furthermore, hBN NPs increased serum disulfide formation by disrupting the thiol/disulfide balance in rats. Also, LOOH and MPO levels increased at high doses, while CAT levels decreased statistically. Conclusion: The results revealed that hBN NPs induce oxidative stress in a dose-dependent manner by modulating thiol/disulfide homeostasis in rats at higher concentrations

Author(s):  
Katarina Mihajlovic ◽  
Isidora Milosavljevic ◽  
Jovana Jeremic ◽  
Maja Savic ◽  
Jasmina Sretenovic ◽  
...  

Ruthenium(II) complexes offer the potential for lower toxicity compared to platinum(II) complexes. Our study aimed to compare cardiotoxicity of [Ru(Cl-tpy)(en)Cl][Cl], [Ru(Cl-tpy)(dach)Cl][Cl], [Ru(Cl-tpy)(bpy)Cl][Cl], cisplatin and saline through assessment of redox status and relative expression of apoptosis-related genes. A total of 40 Wistar albino rats were divided into five groups. Ruthenium groups received intraperitoneally single dose of complexes (4 mg/kg/week) for 4-weeks period; cisplatin group received cisplatin (4 mg/kg/week) and control group received saline (4 mL/kg/week) in the same manner as ruthenium groups. In collected blood and heart tissue samples, spectrophotometrically determination of oxidative stress biomarkers was performed. The relative expression of apoptosis-related genes (Bcl-2, Bax, and caspase-3) in hearts was examined by RT-PCR. Our results showed that systemic and cardiac pro-oxidative markers (TBARS and NO2-) were significantly lower in ruthenium groups compared to cisplatin group, while concentrations of antioxidative parameters (CAT, SOD, and GSSG) were significantly higher. Ruthenium administration led to significantly lower gene expression of Bax and caspase-3 compared to cisplatin-treated rats, while Bcl-2 remained unchanged. Applied ruthenium complexes have less pronounced potential for induction of oxidative stress-mediated cardiotoxicity compared to cisplatin. These findings may help for future studies that should clarify the mechanisms of cardiotoxicity of ruthenium-based metallodrugs.


Small ◽  
2021 ◽  
pp. 2008062
Author(s):  
Yongliang Chen ◽  
Xiaoxue Xu ◽  
Chi Li ◽  
Avi Bendavid ◽  
Mika T. Westerhausen ◽  
...  

2021 ◽  
Author(s):  
James Nyirenda ◽  
Gershom B. Lwanga ◽  
Kaampwe M. Muzandu ◽  
David K. Chuba ◽  
Gibson M. Sijumbila

Abstract Ethnopharmacological relevanceAnemia is a very serious condition in Zambia. One of the plants that has been used traditionally is Phyllanthus muellerianus where different parts of shrub are used to treat a number of diseases in Zambian folklore medicine. Earlier studies have investigated medicinal properties of its aqueous root extracts. This study evaluated the effect of P. muellerianus roots on the hematological indices of albino rats and determined its phytochemical profile. Aim of the studyTo carry out phytochemical screening of the root extract and assess the ant-anemic effect of the aqueous extract on laboratory rats with tail-bled induced anemia Materials and MethodsThirty-six male albino rats placed in six groups were used for the study. The groups comprised the 100, 200, and 400 mg/kg plant extract, Ranferon (200 mg/kg) positive control, anemic non treated control and a normal (non-anemic) control. Anemia, induced through bleeding of the rats, was defined as hemoglobin (Hb) levels less than 12 g/dL. The anti-anemic potential of the plant was determined by comparing its effect on the hematological parameters of rats on treatment to that of the control group.ResultsAfter treatment, rats on the 400 mg/kg plant extract dose showed the greatest increase in the mean values for Hb, Packed cell volume (PCV) and RBC count were 43.3±1.2%, 15.4±0.3 g/dL and 6.3±0.3 x106 /mL respectively, when compared to the negative control group (P < 0.05). Phytochemical screening revealed positive results for alkaloids, flavonoids, saponins, glycosides, steroids, triterpenoids and tannins with varying amounts.Conclusions. The aqueous root extract of P. muellerianus was efficacious against anemia in a dose-dependent manner. The phytochemical compositions seem to be responsible for its hematopoietic properties. Thus, the root decoction of P. muellerianus is useful in alleviating anemia and the results lend credence to its use in traditional medicine in the management of anemia.


2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Xinxin Yang ◽  
Haibo Yang ◽  
Fengdi Wu ◽  
Zhipeng Qi ◽  
Jiashuo Li ◽  
...  

Excessive manganese (Mn) can accumulate in the striatum of the brain following overexposure. Oxidative stress is a well-recognized mechanism in Mn-induced neurotoxicity. It has been proven that glutathione (GSH) depletion is a key factor in oxidative damage during Mn exposure. However, no study has focused on the dysfunction of GSH synthesis-induced oxidative stress in the brain during Mn exposure. The objective of the present study was to explore the mechanism of Mn disruption of GSH synthesis via EAAC1 and xCT in vitro and in vivo. Primary neurons and astrocytes were cultured and treated with different doses of Mn to observe the state of cells and levels of GSH and reactive oxygen species (ROS) and measure mRNA and protein expression of EAAC1 and xCT. Mice were randomly divided into seven groups, which received saline, 12.5, 25, and 50 mg/kg MnCl2, 500 mg/kg AAH (EAAC1 inhibitor) + 50 mg/kg MnCl2, 75 mg/kg SSZ (xCT inhibitor) + 50 mg/kg MnCl2, and 100 mg/kg NAC (GSH rescuer) + 50 mg/kg MnCl2 once daily for two weeks. Then, levels of EAAC1, xCT, ROS, GSH, malondialdehyde (MDA), protein sulfhydryl, carbonyl, 8-hydroxy-2-deoxyguanosine (8-OHdG), and morphological and ultrastructural features in the striatum of mice were measured. Mn reduced protein levels, mRNA expression, and immunofluorescence intensity of EAAC1 and xCT. Mn also decreased the level of GSH, sulfhydryl, and increased ROS, MDA, 8-OHdG, and carbonyl in a dose-dependent manner. Injury-related pathological and ultrastructure changes in the striatum of mice were significantly present. In conclusion, excessive exposure to Mn disrupts GSH synthesis through inhibition of EAAC1 and xCT to trigger oxidative damage in the striatum.


Author(s):  
Mohammed Aliyu Sulaiman ◽  
Daniel Dahiru ◽  
Mohammed Auwal Ibrahim ◽  
Ahmed Ibrahim Hayatu

Background: Oxidative stress is involved in the pathogenesis of hypertension, myocardial ischemia-reperfusion injury, atherosclerosis, muscular dystrophy, aging and other associated diseases. Vitex doniana is used in Adamawa, northern Nigeria to treat oxidative stress associated diseases. However, the antioxidative effects of the plant have not been scientifically examined in oxidative stress experimental animal models. The aim of this study is to investigate the in vitro and in vivo antioxidant activities of aqueous and ethanol stem bark extracts of Vitex doniana in oxidative stress model of rats. Methods: The study used 35 adult albino rats weighing 175 ± 25 g, of which 30 were induced with oxidative stress by intraperitoneal injection of doxorubicin (10 mg/kg) for three consecutive days. Animals were treated by oral administration of silymarin (100 mg/kg) and Vitex doniana aqueous or ethanol extract (100 mg/kg and 200 mg/kg) for 14 consecutive days before they were sacrificed on the 15th day and blood was analyzed for biochemical indices of oxidative stress. Results: The results of the phytochemistry showed the presence of alkaloids, tannins, flavonoids, steroids, phenols, saponins, terpenoids, glycosides: and total flavonoids (52.70 ± 1.60 mg/ml and 75.40 ± 0.80 mg/ml), total phenols (21.45 ± 1.54 mg/ml and 26.50 ± 1.22 mg/ml) for aqueous and ethanol stem bark extracts respectively. The extracts scavenged DPPH radical, reduced Fe3+ and inhibited lipid peroxidation. Doxorubicin significantly (p<0.05) lowered the levels of SOD, CAT, GR and TAS and significantly (p<0.05) but, increased the level of LPO. Oral treatment with Vitex doniana extracts significantly (p<0.05) increased the activities of CAT, GR, SOD and TAS while LPO was significantly (p<0.05) lowered. Vitex doniana stem bark extracts significantly (p<0.05) improved the biochemical derangements observed in the induced untreated animals in comparable manner to that of Silymarin. Conclusion: The present study provides the scientific rationale for the use of Vitex doniana stem bark in traditional medicine and has a viable antioxidative capacity both in vitro and in vivo.


Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Daniel N Meijles ◽  
Imad Al Ghouleh ◽  
Sanghamitra Sahoo ◽  
Jefferson H Amaral ◽  
Heather Knupp ◽  
...  

Organismal aging represents an independent risk factor underlying many vascular diseases, including systemic and pulmonary hypertension, and atherosclerosis. While the mechanisms driving aging are largely elusive, a steady persistent increase in tissue oxidative stress has been associated with senescence. Previously we showed TSP1 elicits NADPH oxidase (Nox)-dependent vascular smooth muscle cell oxidative stress. However mechanisms by which TSP1 affects endothelial redox biology are unknown. Here, we tested the hypothesis that TSP1 induces endothelial oxidative stress-linked senescence in aging. Using rapid autopsy disease-free human pulmonary (PA) artery, we identified a significant positive correlation between age, protein levels of TSP1, Nox1 and the cell-cycle repressor p21cip (p<0.05). Age also positively associated with increased Amplex Red-detected PA hydrogen peroxide levels (p<0.05). Moreover, treatment of human PA endothelial cells (HPAEC) with TSP1 (2.2nM; 24h) increased expression (~1.9 fold; p<0.05) and activation of Nox1 (~1.7 fold; p<0.05) compared to control, as assessed by Western blot and SOD-inhibitable cytochrome c reduction. Western blotting and immunofluorescence showed a TSP1-mediated increase in p53 activation, indicative of the DNA damage response. Moreover, TSP1 significantly increased HPAEC senescence in a p53/p21cip/Rb-dependent manner, as assessed by immunofluorescent detection of subcellular localization and senescence-associated β-galactosidase staining. To explore this pathway in vivo, middle-aged (8-10 month) wild-type and TSP1-null mice were utilized. In the TSP1-null, reduced lung senescence, oxidative stress, Nox1 levels and p21cip expression were observed compared to wild-type supporting findings in human samples and cell experiments. Finally, prophylactic treatment with specific Nox1 inhibitor NoxA1ds (10μM) attenuated TSP1-induced HPAEC ROS, p53 activation, p21cip expression and senescence. Taken together, our results provide molecular insight into the functional interplay between TSP1 and Nox1 in the regulation of endothelial senescence, with implications for molecular control of the aging process.


INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (09) ◽  
pp. 67-74
Author(s):  
Gana Manjusha Kondepudi ◽  
Battu Ganga Rao ◽  
P Balakrishnaiah

The main aim of this study was to screen the selected fruit peel extracts and their polyherbal mixture (PHM) for hepatoprotective activity. Male wistar albino rats (180-200 g), divided into 12 groups after induction of hepatotoxicity, were treated with selected fruit peel extracts and PHM and at the end of 14th day blood and liver samples were collected and analysed. The aqueous peel extract of Malus pumila was a better hepatoprotective among the selected peel extracts. The activities might be due to the conditioning of hepatocytes by protecting the integrity of the membrane from CCl4 induced leakage of serum markers into circulation. All the selected plant extracts and PHM were shown to revert back the liver enzymes to the normal values in diseased rats in a dose dependent manner. In conclusion, the selected fruit peel extracts and poly herbal mixture can be a potent hepatoprotective agent due to their antioxidant and anti-inflammatory actions.


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