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1.
Side effects of cisplatin, especially dose-dependent nephrotoxicity, are major factors limiting its use in cancer.Boldine ((S)-2, 9-dihydroxy-1, 10-dimethoxy-aporphine) is a natural alkaloid known for its strong antioxidant activitypresent in leaves/bark of boldo tree (Peumus boldus Molina), a native tree in Chile. Here, we aimed to investigate thenephroprotective effect of boldine and its underlying mechanisms on cisplatin-induced rat renal injury. Thirty Wistaralbino rats divided into 5 groups (Control, Cis, Bold.40, Cis + Bold.20, Cis + Bold.40 groups) were used. Rats receivedboldine (20 or 40 mg/kg/day), or vehicle (saline) intraperitoneal for 14 days and a single dose cisplatin (7 mg/kg, ip)was applied on the 10th day to induce nephrotoxicity. Rats and kidney tissue were weighed to determine kidneyindex. Blood urea nitrojen (BUN) and creatinine levels, the amount of thiobarbituric acid reactive substances (TBARS,an index of lipid peroxidation), superoxide dismutase (SOD), glutathione peroxidase (GPx) enzyme activities andtumor necrosis factor alpha (TNF-α) levels were measured and histopathologic examination was performed. Induciblenitric oxide synthase (iNOS) and caspase-3 expressions were detected immunohistochemically. Nephrotoxicityinduced by cisplatin was apparent by elevated levels of BUN, creatinine, kidney index, TBARS and TNF-α, anddecreased body weight, SOD and GPx enzyme levels. Pretreatment with boldine protected the renal function at bothboldine doses by fixing the renal damage markers, oxidative stress, caspase-3 and iNOS expression. Histopathologicalfindings supported biochemical findings. Taken together these findings indicate that boldine has promising protectiveeffect against cisplatin nephrotoxicity by improving oxidative stress, inflammation, histopathological alterations andby alleviating caspase 3 expression. 相似文献
2.
Genomic instability and mutations caused by increases in oxidative stress during pregnancycan damage the fetoplacental unit and can upshot preterm birth. Oxidative damage to DNA may possiblybe involved in etiology of preterm birth (PTB) which can be repaired by DNA repair gene. In the presentstudy, we assessed the association of base excision repair gene family by analyzing the association ofsingle nucleotide polymorphisms and genes expression in 8-oxoguanine glycosylase-1 (OGG1) andapurinic-apyrimidinic endonuclease 1 ( APE1) genes with risk of preterm birth in Saudi women. Weanalyzed genotypes of four single nucleotide polymorphisms (SNPs) (rs1052133, rs293795, rs2072668 andrs2075747) in OGG1 gene and three SNPs (rs1130409, rs3136814, and rs3136817) in APE1 gene usingTaqMan Genotyping assay kits in 50 pairs of preterm cases and individually matched controls. Also, geneexpression level was explored by RT-PCR in 10 pairs of preterm placental tissues and individually matchednormal placental tissues. Two OGG1 SNP, rs1052133 (OR=0.497; c2=1.11; p=0.292) and rs2072668(OR=0.408; c2=1.90; p=0.167) and one APE1 SNP rs3136817 (OR=0.458; c2=0.40; p=0.527) showed nonsignificant protective effect against PTB development. The expression of both genes under study wasfound lower in the PTB patients. Genotype and allele frequencies of both gene SNPs did not show anyassociation with the risk of preterm delivery in Saudi women ( P˃0.05). However, synthesis and release of OGG1 and APE1 proteins decreased in preterm placental tissues compared to term delivery reflects theprobability of being one of the mechanisms leading to preterm birth. 相似文献
3.
Fibrosis is the end-stage change of damaged tissues in various human diseases, which can lead to permanent scarring or organ malfunction. Hypoxia leads to oxidative stress, mitochondrial dysfunction, and inflammation in dysfunctional organs and tissues. Oxidative stress resulting from the overproduction of reactive oxygen species plays a central role in the fibrosis of injured organs. This review addresses the updated knowledge of the relationship between hypoxia and tissue fibrosis mediated by the reactive oxygen species pathway. Moreover, novel anti-fibrotic strategies are discussed, which may suppress reactive oxygen species and organ fibrosis. 相似文献
4.
Diabetic nephropathy (DN) is the most frequent cause of chronic renal failure. Until now, thepathophysiological mechanisms that determine its development and progression have not yet been elucidated. In thepresent study, we evaluate the role of autophagy at early stages of DN, induced in type 2 diabetes mellitus (T2DM)mouse, and its association with proximal tubule membrane endocytic receptors, megalin and cubilin. In T2DManimals we observed a tubule-interstitial injury with significantly increased levels of urinary GGT and ALP, but anabsence of tubulointerstitial fibrosis. Kidney proximal tubule cells of T2DM animals showed autophagic vesicleslarger than those observed in the control group, and an increase in the number of these vesicles marked with LBPAby immunofluorescence. Furthermore, a significant decrease in the ratio of LC3II/LC3I isoforms and in p62 proteinexpression in DN affected animals is shown. Finally, we observed a marked increase in urinary albumin and vitamin Dbinding-protein levels in T2DM animals as well as a significant decrease in expression of megalin in the renal cortex.These results indicate an alteration of the tubular endocytic transporters in DN, which could be related to autophagicdysfunction, which would in turn result in impaired organelle recycling, thus contributing to the progression of thisdisease. 相似文献
5.
Cantharidin (CTD) is a bioactive ingredient isolated from Cantharis vesicatoria (blister beetles), which has potential therapeutic value as an anticancer agent. Magnesium Demethylcantharidate (MDC) is a recently developed derivative of Cantharidin (CTD), and previous studies have illustrated its excellent anticancer activity on HCC cells. However, the effect and mechanism of MDC remains unclear and need to be further studied. In particular, whether MDC can cause ER stress in HCC is still unknown. In this study, we demonstrated that endoplasmic reticulum stress (ERS)-related proteins were changed in SMMC-7721 and Bel-7402 cells after being exposed to MDC. Moreover, we found that MDC could significantly inhibit the growth of xenograft tumor in nude mice. In summary, we confirmed that MDC could induce ERS in HCC cells and thus induce apoptosis. 相似文献
6.
Post-resuscitation myocardial dysfunction (PRMD) is the most severe myocardial ischemia-reperfusion injury(MIRI) and is characterized by difficult treatment and poor prognosis. Research has shown the protective effects of therational use of ivabradine (IVA) against PRMD; however, the molecular mechanisms of IVA remain unknown. In thisstudy, an ischemia-reperfusion injury (IRI) model was established using hypoxic chambers. The results demonstratedthat pretreatment with IVA reduced IRI-induced cytotoxicity and apoptosis. IVA attenuated mitochondrial damage,eliminated excess reactive oxygen species (ROS), suppressed IRI-induced ATP and NAD +, and increased theAMP/ATP ratio. We further found that IVA increased the mRNA levels of sirtuin 1 ( SIRT1) and peroxisomeproliferator-activated receptor-γ coactivator 1α ( PGC-1α) and upregulated the expression levels of phosphorylatedAMP-activated protein kinase (p-AMPK)/AMPK, SIRT1, and PGC-1α proteins. Interestingly, no change in AMPKmRNA levels was observed. Cardiomyocyte energy metabolism significantly changed after IRI. The aim of this studywas to demonstrate the cardioprotective effect of Ivabradine via the AMPK/SIRT1/PGC-1α signaling pathway inmyocardial ischemia/reperfusion injury-induced in H9c2 cell. 相似文献
7.
The endoplasmic reticulum (ER) is the site of entry of all proteins that function in the secretory pathway including the extracellular environment. Because it controls the folding of newly synthesized secretory proteins, the ER is indispensable for the maintenance of proteostasis in the secretory pathway. Within the ER and, in part, in post-ER compartments, the quality control of protein folding is under the regulation of the unfolded protein response (UPR) pathways. The UPR strategy is to enhance protein folding, increase the ER degradation pathway of misfolded proteins, and allow the exit from the ER of only correctly folded proteins. The latter is controlled by the multimeric complex COPII, which also provides some of the components for ER-phagy the only route for the disposal of protein aggregates. In this overview, we wish to contribute to the introduction of new perspectives in the study of the mechanisms underlying the control of proteostasis within the secretory pathway. 相似文献
8.
Fluoride is a key ingredient of many psychiatric drugs like fluoxetine (Prozac ®, Fluoxetine ®). Pregnant womenfrequently use this drug as they suffer from depression and anxiety disorders during this period. Fluoxetine is able toreach the fetus through the placenta and passes to the newborn through milk. In the present study, female Wistar ratswere treated with 5, 10, and 20 mg/L fluoxetine (containing 94% fluorides) from pregnancy day 10 to day 20. Afterdelivery, the levels of the enzymatic antioxidants in the brain of their offspring at postnatal day 2 were measured. Theresults showed that, in all fluoxetine exposed groups compared with the control group, there was a significant decrease( P < 0.01) in the glutathione, catalase, glutathione S-transferases and potassium and a non- significant increase ( P >0.05) in the activity of malondialdehyde and creatine kinase. The results suggest that fluoxetine may be a developmentalneurotoxicant due to presence of fluoride hence must be used carefully during pregnancy. 相似文献
9.
Diabetes mellitus (DM) could negatively affect patients’ health via inducing a lot of serious functional hazards in many tissues’ cells at molecular levels. Recently, many scientists had proposed stem cell therapy being an appropriate alternative treatment protocol for numerous health threatening issues including diabetes. Therefore, the current study was designed to investigate the antioxidant potentiality of two MSCs types in alleviating tissues’ oxidative stress dramatic elevation resulting as a consequence of Type 1 DM induction. In our 4 weeks study, animals were divided into four groups: control group, STZ-diabetic group (D), D+AD-MSCs group and D+BM-MSCs group. Data reported that diabetic rats treated with either AD-MSCs or BM-MSCs exhibited a marvelous body tissues (Pancreas, Liver and Kidney) enhancing capabilities in attenuating the oxidative stress status; as evidenced by XO, ROS, and MDA levels down-regulation; with a general concomitant elevation in the antioxidants’ content; evidenced by many enzymatic and non-enzymatic antioxidants up-regulation; relative to the diabetic untreated group. Interestingly, comparing both treatments with each other and to control group, most of the measured parameters were reverted back to near normal levels after AD-MSCs injection; which clearly point out their stunning health benefits and superiority as anti-diabetic agent in overcoming different tissues’ complications; owing to their marked cytoprotective and regenerative potentialities. 相似文献
10.
The current study investigated the comparative oxidative damage in two maize seedlings induced by saline, drought,and combined stress and the ameliorative role of two different doses (20 and 80 µM) of 5-aminolevulinic acid (ALA) againstthe above-mentioned stresses. Hydroponically grown 10-day-old maize ( Zea mays, var. BARI Hybrid Maize-7 (BHM-7) andBARI Hybrid Maize-9 (BHM-9)) seedlings were exposed to 12 dS/m of saline solution, 200 mM mannitol-induced droughtstress alone and their combined stress for 7 days. Result revealed that individual stresses retard the plant growth to somedegrees; however, their combined stress has more detrimental effects, which might be correlated with lipid peroxidation(MDA)-induced oxidative stress in seedlings, enhanced Na +/K + ratio, and augmented generation of superoxide (O 2•−) andhydrogen peroxide (H 2O 2). In contrast, exogenous ALA supplementation at 20 µM concentration markedly recoveredfrom chlorosis and growth inhibition, substantially scavenged reactive oxygen species (ROS) and MDA by preserving ionhomeostasis and relaxing oxidative stress; also, by boosting catalase (CAT) and glutathione S-transferase (GST), andexclusively via depressing the activity of lipoxygenase (LOX) antioxidant enzyme. On the contrary, 80 µM ALA madethings worse; nevertheless, higher activities shown by other antioxidant enzymes; like, superoxide dismutase (SOD),ascorbate peroxidase (APX), peroxidase (POD), and glutathione peroxidase (GPX), which were related to lessen theoxidative damage by highly produced O 2•− and H 2O 2 under combined stress. Non-denaturing gel electrophoresiswas done for further confirmation. However, ALA importantly increased the photosynthetic pigment contents inboth genotypes irrespective of doses. Nevertheless, GST might have assisted the plants to escape from the herbicidaleffect by detoxification. However, in the combined stress condition, high ALA concentration may have somepositive role to play. Our findings also showed that BHM-9 performed better than BHM-7. Therefore, ALA atlower concentration was effective for single stress of saline and drought, while higher concentration can improveplant survival under combined stress. 相似文献
13.
分析了某公司的2#乙二醇R-120环氧乙烷反应器中C-11环焊缝开裂原因。对开裂C-11环焊缝开展了化学成分、金相观察、硬度测试、断口微观观察、EDS能谱分析等试验研究。试验发现:壳程、管板母材和焊缝金属化学成分分别满足SA543 Type B CL.1,SA508 Gr.4N CL.1和MGS 80的要求;从内壁管板侧热影响区起裂的主裂纹穿晶扩展,裂纹尖端沿晶扩展并有分叉,具有应力腐蚀裂纹特征;内壁附近焊缝两侧热影响区局部有马氏体组织;管板侧热影响区硬度最高为466.3 HV10;断口观察发现裂纹在内壁产生,是多源裂纹,沿壁厚向外壁扩展15 mm,断口上有冰糖状等轴晶和柱状晶;裂纹断口探测到P和Na元素。该反应器开裂原因是由于焊接导致在管板与壳程焊接区域存在较高的残余应力,在高温锅炉水介质中,发生了应力腐蚀开裂,由内壁向外扩展,最终导致泄漏。 相似文献
15.
The wound is induced by several mechanical and metabolic factors. In the etiology of the wound recovery,excessive oxidative stress, calcium ion (Ca 2+) influx, and apoptosis have important roles. Ca 2+-permeable TRPM2 channel is activated by oxidative stress. Protective roles of Hypericum perforatum extract (HP) on the mechanical nerve injury-induced apoptosis and oxidative toxicity through regulation of TRPM2 in the experimental animals wererecently reported. The potential protective roles in HP treatment were evaluated on the TRPM2-mediated cellularoxidative toxicity in the renal epithelium (MPK) cells. The cells were divided into three groups as control, wound,and wound + HP treatment (75 µM for 72 h). Wound diameters were more importantly decreased in the wound+HPgroup than in the wound group. In addition, the results of laser confocal microscopy analyses indicated protectiveroles of HP and TRPM2 antagonists (N-(p-Amylcinnamoyl) anthranilic acid and 2-aminoethyl diphenylborinate)against the wound-induced increase of Ca 2+ influx and mitochondrial ROS production. The wound-induced increaseof early (annexin V-FITC) apoptosis and late (propidium iodide) apoptosis were also decreased in the cells by the HPtreatment. In conclusion, HP treatment acted protective effects against wound-mediated oxidative cell toxicity andapoptosis through TRPM2 inhibition. These effects may be attributed to their potent antioxidant effect. 相似文献
16.
Heat stress (HS) reaction can lead to serious physiological dysfunction associated with cardiovascular andvarious organ diseases. Ginsenoside Rg3 (G-Rg3) is a representative component of ginseng rare saponin and canprotect against multiple organs, also used as functional food to adjust the balance of the human body, but thetherapeutic effect and molecular mechanism of G-Rg3 on male diseases under HS are underexplored. The aim ofthe present study, G-Rg3 was prepared through the efficient conversion of ginsenoside Rd and investigate thecontribution of G-Rg3 to testicular injury induced exposure to HS. All mice were divided into four groups as follows:normal group, HS group, and HS+G-Rg3 (5 and 10 mg/kg) groups. G-Rg3 was administered orally for 14 days, thenexposed to a single scrotal heat treatment (43°C, 18min) on the 7th day. After HS treatment, the morphology of testisand epididymis changes, and caused a significant loss of multinucleated giant cells, desquamation of germ cells indestructive seminiferous tubules, and degenerative Leydig cells, further destroying the production of sperm. Afteradministration G-Rg3 (5 and 10 mg/kg/day) for 2 weeks, the spermatogenic-related indexes of testosterone levels andsuperoxide dismutase (SOD) activity, glutathione (GSH) content significantly ( p < 0.01) increase compared with theHS group. Moreover, G-Rg3 treatment effectively ameliorated the production of malondialdehyde (MDA) ( p < 0.05 or p < 0.01). Importantly, G-Rg3 exhibited the protective potential against HS-induced injury not only suppressing theprotein levels of heme oxygenase-1 (HO-1), hypoxia-inducible factor-1α (HIF-1α), and heat shock protein 70 (HSP70)but also modulating the Bcl-2 family ( p < 0.01 or p < 0.001) and activation of mitogen-activated protein kinase(MAPK) signaling pathways ( p < 0.01). For most of the parameters tested, the HS+G-Rg3 (10 mg/kg) group exhibitedpotent effects compared with those exhibited by the low dose (5 mg/kg) group. In conclusion, the present studydemonstrated that G-Rg3 exerted protective effects against HS-induced testicular dysfunction via inhibiting theMAPK-mediated oxidative stress and apoptosis in mice. 相似文献
17.
Cadmium (Cd) causes oxidative stress, which leads to the oxidation of various biomolecules by the production of reactive oxygen species (ROS) to facilitate programmed cell death (PCD). The antioxidant defense system fails to detoxify ROS when it is produced in excess. Nitric oxide (NO), a gaseous free radical and a phytohormone, regulates various physiological processes of plants. Therefore, this work was undertaken to study the effects of the application of exogenous sodium nitroprusside (SNP, a NO donor) on growth parameters, oxidative stress, accumulation of secondary metabolites, and activities of antioxidant enzymes under Cd stress. Mild (50 µM) and severe (200 µM) Cd stress were applied to hydroponically grown pea (Pisum sativum L.) plants with or without 50 µM SNP. Severe Cd stress had a substantial impact on the plants. The effectiveness of NO in reducing Cd-induced negative effects on plant height, fresh weight, dry weight, protein content, nitrite content, nitrate reductase (NR) activity, catalase activity, and peroxidase activity were investigated. Seedling development, protein content, nitrite content, nitrate reductase (NR) activity, antioxidant defense systems disruption, overproduction of reactive oxygen species, and oxidative damage were observed. The antioxidant defense system (catalase and peroxidase activities) was activated by NO, which resulted in lower lipid peroxidation and lower hydrogen peroxide (H2O2) levels in Cd-exposed plants. SNP treatment boosted endogenous NO levels and NR activity in Cd-stressed plants while also enhanced proline levels to preserve osmotic equilibrium. The presence of total phenols and flavonoids increased after SNP treatment, indicating that SNP enhanced stress recovery and boosted plant development in Cd-stressed plants. 相似文献
18.
A potted experiment was carried out to study the effect of an arbuscular mycorrhizal fungus ( Diversisporaversiformis) and arbuscular mycorrhizal like fungus ( Piriformospora indica) on antioxidant enzyme defense system ofSatsuma orange ( Citrus sinensis cv. Oita 4) grafted on Poncirus trifoliata under favourable temperature (25°C) andcold temperature (0°C) for 12 h. Such short-term treatment of cold temperature did not cause any significant changein root fungal colonization and spore density in soil. Under cold stress, D. versiformis inoculation did not change theactivity of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) in leaves and roots, whereas P. indicainoculation significantly increased the activity of CAT in roots and POD in leaves only. In addition, inoculation oftwo mycorrhizal fungi under cold stress significantly increased the relative expression levels of PtPOD and PtF-SODin leaves, P. indica up-regulated the expression levels of PtCu/Zn-SOD in leaves, and D. versiformis also induced theexpression levels of PtMn-SOD and PtCAT1 in leaves. In addition, inoculated Oita 4 trees maintained significantlylower hydrogen peroxide levels and malondialdehyde contents in leaves and roots under cold temperature, suggestinglower oxidative damage. Therefore, we concluded that arbuscular mycorrhizal fungi (especially P. indica) mainlyinduced the expression of antioxidant enzyme genes, depending on the fungal species, and thus mitigated oxidativedamage for higher cold resistance in inoculated plants. 相似文献
19.
This study aimed to assess the preventive effects of thyme oil and thymol on doxorubicin (DOX)-inducedrenotoxicity, cardiotoxicity, and oxidative stress in Wistar rats. Thyme oil was subjected to GC-MS analysis, whichindicated that thymol was the major constituent representing 33.896%. Rats intraperitoneally injected with DOX ata dose of 2 mg/kg b.w./one per week for 7 weeks were co-treated with thyme oil and its major constituent, thymol, atdoses 250 and 100 mg/kg b.w./every other day, respectively, by oral gavage for the same period. Thyme oil and thymolmarkedly ameliorated the raised levels of serum urea, uric acid, and creatinine in DOX-administered rats. They alsoreduced the elevated activities of serum CK-MB and LDH. Thyme oil was more effective than thymol in decreasingthe elevated serum creatinine level and serum CK-MB activity in DOX-administered rats, thereby reflecting its morepotent effect on kidney and heart functions. Lipid peroxidation significantly decreased while GSH level and GST andGPx activities significantly increased in kidney and heart of DOX-administered rats treated with thyme oil and thymol.The DOX-induced perturbed kidney histological changes including congestion of glomerulus tuft, inflammatory cellsinfiltration, protein cast in lumina of the renal tubule, and thickening of the parietal layer of Bowman’s capsule wereremarkably ameliorated as a result of treatment with thyme oil and thymol; thyme oil was more effective. In addition,DOX-induced deleterious heart histological alterations, including intramuscular infiltration of inflammatory cells,focal necrosis of cardiac myocytes, and edema, were remarkably reduced by treatment with thyme oil and thymol.Thus, it can be concluded that DOX could induce marked toxicity in kidney and heart, and the treatment with thymeoil or thymol produced potential improvement of kidney and heart function and histological integrity via repression ofoxidative stress and enhancement of antioxidant defense mechanisms. 相似文献
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