Metabonomic analysis of the protective effect of quercetin on the toxicity induced by mixture of organophosphate pesticides in rat urine

2016 ◽  
Vol 36 (5) ◽  
pp. 494-507 ◽  
Author(s):  
L Qi ◽  
C Cao ◽  
L Hu ◽  
S Chen ◽  
X Zhao ◽  
...  

The present study aims to investigate the protective effect of quercetin against the joint toxic action induced by the mixture of four organophosphate pesticides (mixture-OPs) (dimethoate, acephate, dichlorvos, and phorate) at their corresponding no observed adverse effect level (NOAEL) using metabonomics. Rats were randomly divided into control, quercetin-treated, mixture-OPs-treated, and quercetin plus mixture-OPs-treated groups. Mixture-OPs and quercetin were given to the rats daily through drinking water and intragastric administration, respectively, for 90 days. The metabonomic profiles of rat urine were analyzed using ultra-performance liquid chromatography–mass spectrometry (UPLC/MS). The 14 metabolites significantly changed in the treatment groups compared with the control group, including the biomarkers of OPs exposure (dimethylphosphate, dimethyldithiophosphate, diethylphosphate) and the metabolites of quercetin (quercetin and isorhamnetina). The intensities of gentisic acid, creatinine, suberic acid, hippuric acid, uric acid, and citric acid significantly decreased, whereas the intensities of 7-methylguanine, estrone sulfate, and cholic acid significantly increased, in the mixture-OPs-treated group compared with the control group ( p < 0.01). The variation tendency of the aforementioned metabolites was significantly ameliorated in the high-dose quercetin (50 mg/(kg bw day)) plus mixture-OPs-treated group compared with the mixture-OPs-treated group ( p < 0.05). However, the intensities of these metabolites in the high-dose quercetin plus mixture-OPs-treated group were still significantly different from those of the control group ( p < 0.05). Results indicated that high dose of quercetin elicits a partial protective effect on the toxicity induced by mixture-OPs, including fatty acid and energy metabolism, antioxidant defense system, DNA damage, and liver and kidney function.

2019 ◽  
Vol 39 (4) ◽  
pp. 524-536
Author(s):  
Y Liu ◽  
X Zhang ◽  
T Guan ◽  
S Jia ◽  
Y Liu ◽  
...  

This study aimed to analyse the protective effects of quercetin on the toxicity of cadmium (Cd) using metabonomics techniques. Sixty male Sprague–Dawley rats were randomly divided into six groups ( n = 10): control group (C), low-dose quercetin-treated group (Q1; 10 mg/kg bw/day), high-dose quercetin-treated group (Q2; 50 mg/kg bw/day), Cd-treated group (D; 4.89 mg/kg bw/day), low-dose quercetin plus Cd-treated group (DQ1) and high-dose quercetin plus Cd-treated group (DQ2). The rats continuously received quercetin and Cd via gavage and drinking water for 12 weeks, respectively. The rat urine samples were collected for metabonomics analysis. Finally, 10 metabolites were identified via the metabonomics profiles of the rat urine samples. Compared with the control group, the intensities of taurine, phosphocreatine, l-carnitine and uric acid were significantly decreased ( p < 0.01) and those of LysoPC (18: 2 (9Z, 12Z)), guanidinosuccinic acid, dopamine, 2,5,7,8-tetramethyl-2(2′-carboxyethyl)-6-hydroxychroman and allantoic acid were significantly increased ( p < 0.01) in the Cd-treated group. However, the intensities of the aforementioned metabolites had restorative changes in the high-dose quercetin plus Cd-treated groups unlike those in Cd-treated group ( p < 0.01 or p < 0.05). Results indicated that quercetin exerts protective effects on Cd-induced toxicity by regulating energy and lipid metabolism, enhancing the antioxidant defence system and protecting liver and kidney function and so on.


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Yumei Liu ◽  
Haojie Wang ◽  
Mengyu Zhang ◽  
Jiajia Wang ◽  
Zhixiang Zhang ◽  
...  

Abstract Background T-2 toxin is a mycotoxin produced by Fusarium species that is highly toxic to animals. Recent studies have indicated that Selenomethionine (SeMet) have protective effect against mycotoxins-induced toxicity. The aim of the present study was to investigate the protective effect of SeMet on T-2-toxin-induced liver injury in rabbit and explore its molecular mechanism. Fifty rabbits (30 d, 0.5 ± 0.1 kg) were randomly divided into 5 groups: control group, T-2 toxin group, low, medium and high dose SeMet treatment group. The SeMet-treated group was orally pretreated with SeMet (containing selenium 0.2 mg/kg, 0.4 mg/kg and 0.6 mg/kg) for 21 days. On the 17th day, T-2 toxin group and SeMet-treated group were orally administered with T-2 toxin (0.4 mg/kg body weight) for 5 consecutive days. Results The results showed that low-dose SeMet significantly improved T-2 toxin-induced liver injury. We found that low-dose SeMet can reduce the level of oxidative stress and the number of hepatocyte apoptosis. Moreover, the levels of Bax, caspase-3 and caspase-9 were significantly reduced and the levels of Bcl-2 were increased. Conclusions Therefore, we confirmed that low-dose SeMet may protect rabbit hepatocytes from T-2 toxin by inhibiting the mitochondrial-caspase apoptosis pathway.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Marwa M. M. Refaie ◽  
Entesar F. Amin ◽  
Nashwa F. El-Tahawy ◽  
Aly M. Abdelrahman

Nephrotoxicity is one of the limiting factors for using doxorubicin (DOX). Interleukin 1 has major role in DOX-induced nephrotoxicity, so we investigated the effect of interleukin 1 receptor antagonist diacerein (DIA) on DOX-induced nephrotoxicity. DIA (25 and 50 mg/kg/day) was administered orally to rats for 15 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of DOX (15 mg/kg) at the 11th day. We measured levels of serum urea, creatinine, renal reduced glutathione (GSH), malondialdehyde (MDA), total nitrites (NOx), catalase, and superoxide dismutase (SOD). In addition, caspase-3, tumor necrosis factor alpha (TNFα), nuclear factor kappa B (NFκB) expressions, and renal histopathology were assessed. Our results showed that DOX-induced nephrotoxicity was ameliorated or reduced by both doses of DIA, but diacerein high dose (DHD) showed more improvement than diacerein low dose (DLD). This protective effect was manifested by significant improvement in all measured parameters compared to DOX treated group by using DHD. DLD showed significant improvement of creatinine, MDA, NOx, GSH, histopathology, and immunohistochemical parameters compared to DOX treated group.


2020 ◽  
Author(s):  
Wenjun Shi ◽  
Fei Yang ◽  
Liting Wang ◽  
Nankun Qin ◽  
Chengxiang Wang ◽  
...  

Abstract BackgroundPlantaginis semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but little was known about its pharmacological mechanism. MethodsThe model was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis semen groups (n = 7). The Plantaginis semen groups were treated orally with Plantaginis semen at 0.9375, 1.875 and 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used as the basis for serum lipidomics analysis, and orthogonal partial least squares discriminant analysis (OPLS-DA) was carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of urate anion transporter 1(URAT1) and phosphatidylinositol 3-kinase/ protein kinases B (PI3K/Akt) were determined by quantitative real-time polymerase chain reaction (RT-qPCR). ResultsCompared with the model group, the levels of serum UA, Cr, and TG were significantly (p<0.01) decreased in benzbromarone and three Plantaginis semen groups and the level of serum TNF-α was significantly (p<0.05) decreased in benzbromarone and low dose of Plantaginis semen group. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was mostly affected. These perturbations can be partially restored via treatment of benzbromarone and Plantaginis semen. Additionally, the URAT1 and PI3K/Akt mRNA expression levels were significantly decreased (p<0.05) after treatment with benzbromarone and high dose of Plantaginis semen. ConclusionsPlantaginis semen had significant anti-HUA, anti-inflammatory and renal protection effects and could attenuate potassium oxonate-induced HUA through regulation of lipid metabolism disorder. Trial registrationNot applicable


1997 ◽  
Vol 15 (6) ◽  
pp. 2312-2321 ◽  
Author(s):  
A M Gianni ◽  
S Siena ◽  
M Bregni ◽  
M Di Nicola ◽  
S Orefice ◽  
...  

PURPOSE To assess the efficacy, toxicity, and applicability of high-dose therapy administered as adjuvant initial treatment to women with breast cancer with extensive nodal involvement. PATIENTS AND METHODS Sixty-seven patients with stage II to III breast cancer involving > or = 10 axillary nodes received a novel high-dose sequential (HDS) regimen, including the high-dose administration of three non-cross-resistant drugs (cyclophosphamide, methotrexate, and melphalan) given within the shortest interval of time as possible with hematologic and nonhematologic toxicity. RESULTS Sixty-three patients completed the program as planned, one patient died of acute toxicity, and three patients were switched to standard-dose adjuvant therapy. After a median follow-up duration of 48.5 months and a lead follow-up of 78 months, actuarial relapse-free survival for all 67 registered patients is 57% and overall survival is 70%, respectively. Comparison with a historical control group of 58 consecutive patients showed a significantly superior rate of freedom from relapse for the HDS-treated group (57% v 41%, respectively), in particular when two subgroups of patients, more homogeneous for their number of involved nodes, were compared (65% v 42%). Overall, treatment was of short duration (median, 70 days), required a median of 32 days of hospital stay, and was associated with only a few severe side effects (the most distressing being oral mucositis after melphalan therapy). CONCLUSION HDS therapy emerges as an effective and applicable regimen, whose major toxicity was occasional. Final assessment of its value in a randomized, multicenter trial is presently underway.


2020 ◽  
Vol 32 (10) ◽  
pp. 914
Author(s):  
M. S. Garcia ◽  
W. A. Orcini ◽  
R. L. Peruquetti ◽  
J. E. Perobelli

This study investigated the reproductive toxicity of methylmercury (MeHg) and Aroclor (Sigma-Aldrich), alone or in combination, following exposure of prepubertal male rats considering the chromatoid body (CB) as a potential target. The CB is an important molecular regulator of mammalian spermatogenesis, primarily during spermatid cytodifferentiation. Male Wistar rats were exposed to MeHg and/or Aroclor , according the following experimental design: control group, which was administered in corn oil (vehicle) only; MeHg-treated group, which was administered 0.5mg kg−1 day−1 MeHg; Aroclor-treated group, which was administered 1mg kg−1 day−1 Aroclor; Mix-LD, group which was administered a low-dose mixture of MeHg (0.05mg kg−1 day−1) and Aroclor (0.1mg kg−1 day−1); and Mix-HD group, which was administered a high-dose mixture of MeHg (0.5mg kg−1 day−1) and Aroclor (1.0mg kg−1 day−1). MeHg was diluted in distilled water and Aroclor was made up in corn oil (volume 1mL kg−1). Rats were administered the different treatments from PND23 to PND53 by gavage, . The morphophysiology of CBs was analysed, together with aspects of steroid hormones status and regulation, just after the last treatment on PND53. In addition, the long-term effects on sperm parameters were assessed in adult animals. MeHg exposure increased mouse VASA homologue (MVH) protein levels in seminiferous tubules, possibly affecting the epigenetic status of germ cells. Aroclor produced morphological changes to CB assembly, which may explain the observed morphological defects to the sperm flagellum and the consequent decrease in sperm motility. There were no clear additive or synergistic effects between MeHg and Aroclor when administered in combination. In conclusion, this study demonstrates that MeHg and Aroclor have independent deleterious effects on the developing testis, causing molecular and morphological changes in CBs. To the best of our knowledge, this is the first study to show that CBs are targets for toxic agents.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4226-4226
Author(s):  
Mohsen Saleh Elalfy ◽  
Iman Ahmed Ragab ◽  
Enas Ahmed Azab ◽  
Shaimaa Nasr ◽  
Marwa Abdel Maguid

Abstract Abstract 4226 Patients with childhood ALL achieve long-term disease-free survival, making reducing complications of therapy of major concerns. The aim of this study was to assess the prevalence and degree of neurocognitive dysfunction in survivors of childhood ALL treated with different protocols and the effect of time since end of chemotherapy. Patients and methods: A cross-sectional study including 60 ALL survivors aged 5–16 years at enrollment; 2–9 years at diagnosis, CNS1, treated through 1998–2008 and regularly followed up in childhood cancer survivors clinic;. They were compared to 20 healthy age and sex matched controls. Grade of school, scholastic achievement in the previous year were reported followed by revision of hospital records including type and risk of ALL, protocol of treatment, number, type and dose of intrathecal chemotherapy, number and doses of high dose I.V methotrexate, data of cranial radiotherapy. Three different protocols were applied to these patients according to the time of diagnosis, patients diagnosed between January 1998 to December 2000 were treated with Modified BFM 83. Those diagnosed between January 2001 to June2004 were treated with BFM 90 protocol, and those diagnosed From July 2004 to June 2008 were treated with CCG 1991 for standard risk and CCG 1961 for high risk patients.Neurocognitive functions were tested using Wechsler Intelligence Scale for Children,Benton visual retention (BVR) test and Trail making test (part A and B were done. MRI Brain was performed to the patients and control group using diffusion weighed images and diffusion tensor magnetic resonance imaging (DTI). Results: Survivors treated with CCG protocol showed a significant decrease in all cognitive tests results compared to control (p<0.05). Survivors treated with BFM 90 protocol had a significant lower total IQ, verbal IQ, TMT-partA, compared to both control and survivors treated with Modified BFM 83, and a significant decrease in performance IQ, BVRT and TMT-partB compared to control only. No significant difference between results of cognitive tests in survivors treated with Modified BFM 83 and control group. Both left and right frontal cortex apparent diffusion coefficient (ADC) was significantly higher in CCG(.88±.060.91±.028) treated group compared to control(.695±.0018.684±.0018), BFM 90(.79±.071.76±.048) and modified BFM 83(.76±.030.83±.023×10&minus;3mm2/s) groups (p<0.05) yet a significant decrease in FA of right frontal cortex only in CCG (.250±.039)treated group compared to control(.684±.0018), BFM 90(.450±.042) and Modified BFM 83(.41±.028) groups(p<0.05). FA of right frontal, was significantly lower in BFM 90 and Modified BFM 83 treated group compared to control group. No significant correlation was found between cognitive tests results with age at diagnosis, time since the end of therapy, total number of intrathecal injections, age at radiotherapy treatment, dose and time of radiotherapy. Cognitive tests didn’t differ between survivors treated with triple intrathecal therapy(ITTT) compared to those treated with intrathecal methotrexate, yet significant decrease in FA of right hippocampus in survivors who received ITTT compared to survivors treated with intrathecal monotherapy, Conclusion: Neurocognitive dysfunction was a common sequelae of childhood ALL treatment. It was more related to protocol of therapy rather than the duration of follow-up since end of chemotherapy. Frontal lobe FA may be a clinically useful biomarker for the assessment of neurotoxicity in post-treatment childhood ALL survivors. Disclosures: No relevant conflicts of interest to declare.


2015 ◽  
pp. 22-7
Author(s):  
Indra Prasetya ◽  
Ria Ashriyah ◽  
Ira Setyawati ◽  
Joko Hermawan ◽  
Widyo Mahargo ◽  
...  

Background : Heart disease is the leading cause of death for both men and women, but heart disease is preventable and controllable. Ganoderma lucidum is widely used as traditional medicine for centuries particularly in China, Japan, and Korea. Previous study showed antioxidative activity of polysaccharide peptide (PsP) from Genoderma lucidum.Objective : This study was aimed to evaluate anti-inflammatory and antioxidant effect of polysaccharide peptide (PsP) from Ganoderma lucidum in atherosclerotic rats.Methods : The atherosclerotic rats were randomly divided into four groups (5 rats each group) : atherosclerotic model with high-fat diet, low dose PsP treated group (50 mg/kgBW), medium dose PsP treated group (150 mg/kgBW), high dose PsP treated group (300 mg/kgBW), with normal mice used as a control group. Parameters measured were the level of MDA, SOD, IL - 6 , IL - 10, hsCRP, TNF - ?, lipid profile and foam cell.Results : After PsP therapy for 5 weeks, the levels of MDA (p=0.01), hsCRP (p=0.018) in rats model of atherosclerosis decrease significantly. PsSP can reduce levels of IL - 6 (p=0.933) and increase levels of SOD (p=0.28) descriptively at PsP doses 150 mg/kgBW. While the levels of TNF-? (p=0.894) and IL-10 (p=0.98) was not affected by administration of PsP. PsP improve the lipid profile by increasing HDL (p=0.002) and lowering total cholesterol (p=0.04). The formation of foam cells (p=0.024) as a marker of atherogenesis significantly decreased by administration of PsP .Conclusion : PSP can be useful to reduce inflammatory processes and oxidative stress to prevent the process of atherogenesis.


2008 ◽  
Vol 32 (2) ◽  
pp. 147-158
Author(s):  
Dalia Ahmed Kalef

To conduct the influence of salinomycin & anticoccidial vaccine onpathological changes in intestine of broiler chickens experimentalinfected with Eimeria spp. By using 40 broiler chicks divided randomlyto four groups( 10 chicks of each group ) First group vaccinated withanticoccidial vaccine (coccivac) at 8 days of age in drinking water whilethe second group feeded salinomycin in concentration 60ppm from oneday old ,the third group left non vaccinated nor given salinomycin as acontrol group at(26 days )of age chicks in that three groups infected withdifferent species of Eimeria spp .with high dose (744x74³) Oocyst /chickby group inoculation & the fourth group consider negative control notvaccinated or treated .At (33 days)of chicks age all the chicks were killedfor measuring lesion score of intestine which their results +1.75 , +3, +4with mortality rate 0%,10%,20% for vaccinated ,salinomycine treated &control groups respectively then took samples for Histopathologicalchanges the results pointed high pathological changes in intestine ofpositive control group with sever necrosis & degeneration of epitheliawith sever tissue damage companied with maturation first & secondgeneration sporozoite in the endothelial layer of intestine. While thepathological changes was less sever in salinomycine treated group withnecrosis & degeneration of epithelial layers accompanied with exist ofsporozoite in endothelial layer of intestine . while the vaccinated groupshowed no clear pathological changes in intestine except hyperplasia ofglobal cells & infiltration of lymphocytes cells in the layers of intestine ,it was concluded that the vaccine which was given to chicks provide goodprotection & decrease dangerous of coccidiosis infection .


2019 ◽  
Vol 17 (2) ◽  
pp. 127 ◽  
Author(s):  
Khadijeh Mirzaei Khorramabadi ◽  
Ali Reza Talebi ◽  
Abolghasem Abbasi Sarcheshmeh ◽  
Aghdas Mirjalili

Background: Generation of free radicals and oxidative stress are a major contributorto diabetes. These factors lead to the development of diabetic testicles disorders.Objective: In this study, the protective effect of vitamin E on functional disordersassociated with diabetes induced oxidative stress in male reproductive systems hasbeen investigated.Materials and Methods: Thirty-three adult male Mice were divided into control,diabetic, and untreated diabetic groups. Streptozotocin was used to induce diabetes.In the treated group, vitamin E was given to the Mice intraperitoneally for 30 days.Then, animals were anesthetized and sacrificed. Animal testicles were isolated andhomogenized in phosphate buffer and used for measuring sperm count, motility andsurvival of sperm, MDA concentration and antioxidant capacity (TAC). Apoptosis wasalso performed with the TUNEL test.Results: The results of reduction (12.03±98.11) TAC, MDA concentration (–28.5±2.58),sperm motility (unstable sperma= 86.4±7.48), sperm count (171.51), Sperm morphology(natural morphology= 49.69±31.93) and abnormal morphology (9.77±49.7)with increased oxidative damage. These changes were statistically significant incomparison with the control group for all variables other than MDA (p= 0.05). Treatmentof vitamin E diabetic Mice improved the ability of antioxidants to prevent oxidativedamage in the testicles, restore the sperm movement, and increase the number ofnormal sperm as well as TAC. The level of apoptosis in the treated group has decreasedcompared to the untreated group.Conclusion: Vitamin E protects the reproductive system against diabetes mellitus.Therefore, it was concluded that vitamin E may be a suitable agent for protecting thesperm and testicular parameters against undesirable effects of diabetes.


Sign in / Sign up

Export Citation Format

Share Document