Alleviation of Cadmium Chloride–Induced Acute Genotoxicity, Mitochondrial DNA Disruption, and ROS Generation by Chocolate Coadministration in Mice Liver and Kidney Tissues

The aim of this study was to investigate the expression of metallothionein genes in the liver and kidneys of rats with acute cadmium poisoning.Simulation of poisoning with cadmium chloride was carried out on white outbred female rats, divided into 4 groups depending on the dose of the injected toxicant. RNA samples isolated from rat liver and kidneys were used as research materials.The multiplicity of expression of the MT3 gene in the kidneys increased at the lowest dose of CdCl2 , which was used in this experiment (0.029 mg / kg); with increasing dosage, the expression level decreased, but not lower than the control values. Analysis of the expression of the same gene in the liver showed a tendency towards a decrease in the content of transcripts with increasing dose. The frequency of expression of the MT2A gene at higher doses of CdCl2 increased both in the liver and in the kidneys.In the present work, statistically significant dose-dependent changes in the expression multiplicity of metallothionein genes were detected 24 hours after CdCl2 administration. The revealed differences in the level of transcriptional activity of metallothionein genes require further investigation, since there are probably differences in the level of gene expression at earlier and later periods of toxicant action.

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Exposure to a “safe” dose of environmental pollutant bisphenol A elevates oxidative stress and modulates vasoactive system in hypertensive rats

Human & Experimental Toxicology ◽

10.1177/09603271211053285 ◽

2021 ◽

pp. 096032712110532

Author(s):

Manigandan Nagarajan ◽

Boobalan Raja ◽

Jeganathan Manivannan

Keyword(s):

Adverse Effects ◽

Bisphenol A ◽

Thiobarbituric Acid ◽

Environmental Pollutant ◽

Ros Generation ◽

Thiobarbituric Acid Reactive Substances ◽

Hypertensive Rats ◽

Liver And Kidney ◽

Ace Activity ◽

Safe Dose

Due to the prevalence of hypertension (one of the major risk factors of CVD) in the population, it is necessary to explore the adverse effects of daily tolerable and “safe” dose of bisphenol A (BPA) under hypertensive conditions. The current study exposed the Nω-nitro-l-arginine methyl ester (L-NAME, 40 mg/kg b.w/day) induced hypertensive Wistar rats to BPA (50 μg/kg b.w/day) by oral administration along with appropriate controls for 30 days period. The results illustrate that a ‘safe’ dose of BPA does not influence the systolic blood pressure (SBP) and levels of circulatory biomarkers of tissue damage. On the other hand, BPA exposure significantly ( p < 0.05) elevates the thiobarbituric acid reactive substances (TBARS) content in plasma and tissues (heart, aorta, liver and kidney) in hypertensive rats when compared with respective control (BPA alone exposed) rats. Similarly, a significant modulation of ROS generation in RBC, plasma nitric oxide (NO) level and angiotensin-converting enzyme (ACE) activity was observed only under hypertensive milieu. In conclusion, the observed adverse effects during ‘safe’ dose of BPA exposure are specific to the hypertensive condition. Therefore, a precise investigation to explore the effects of BPA exposure in vulnerable hypertensive populations is highly suggested.

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Abstract 11852: Role of Lox-1 in Mitochondrial Dna Damage and NLRP3 Inflammasome Activation

Circulation ◽

10.1161/circ.130.suppl_2.11852 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Zufeng Ding ◽

Sadip Pant ◽

Abhishek Deshmukh ◽

Jawahar L Mehta

Keyword(s):

Dna Damage ◽

Mitochondrial Dna ◽

Nlrp3 Inflammasome ◽

Ros Generation ◽

Inflammasome Activation ◽

Mtdna Damage ◽

Mitochondrial Dna Damage ◽

Mitochondrial Ros ◽

Nlrp3 Inflammasome Activation

Objective: This study tested the hypothesis that mitochondrial DNA damage could trigger NLRP3 inflammasome activation during inflammation, and LOX-1 may play a critical role in this process. Methods and Results: We performed studies in cultured human THP1 macrophages exposed to ox-LDL or LPS,which are often used as inflammation stimuli in vitro . We examined and confirmed the increase in LOX-1 expression when cells were treated with ox-LDL or LPS. Parallel groups of cells were treated with LOX-1 Ab to bind LOX-1. In accordance with our previous studies in endothelial cells and smooth muscle cells, LOX-1 Ab markedly reduced ox-LDL- as well as LPS-stimulated LOX-1 expression. To assess mitochondrial ROS generation, MitoSOX™ Red mitochondrial superoxide indicator was used. Both fluorescence staining and flow cytometry analysis showed that LPS induced (more than ox-LDL) mitochondrial ROS generation. Pretreatment with LOX-1 Ab significantly attenuated mitochondrial ROS generation in response to ox-LDL or LPS. Then we observed mtDNA damage in THP1 cells exposed to ox-LDL or LPS. Importantly, pretreatment with LOX-1 Ab protected mtDNA from damage in response to both stimuli. This was also confirmed by q-PCR (mtDNA/nDNA ratio) analysis. Further, ox-LDL or LPS induced the expression of phos-NF-kB p65, caspase-1 p10 and p20, and cleaved proteins IL-1β and IL-18. Of note, NLRP3 inflammasome was activated in response to ox-LDL or LPS in a similar manner. Pretreatment of cells with LOX-1 Ab treatment blocked or significantly attenuated these inflammatory responses. Conclusions: These observations based on in vitro observations indicate that LOX-1 via ROS generation plays a key role in mtDNA damage which then leads to NLRP3 inflammasome activation during inflammation.

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Single or combined cadmium and aluminum intoxication of mice liver and kidney with possible effect of zinc

The Journal of Basic & Applied Zoology ◽

10.1016/j.jobaz.2016.12.004 ◽

2016 ◽

Vol 77 ◽

pp. 91-101 ◽

Cited By ~ 13

Author(s):

Ahmed S. Ibraheem ◽

Amin A. Seleem ◽

Mohamed F. El-Sayed ◽

Basma H. Hamad

Keyword(s):

Liver And Kidney ◽

Mice Liver ◽

Aluminum Intoxication

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Incorporation of tritiated thymidine into mitochondrial DNA of the liver and kidney cells of chickens and mice in tissue culture

Histochemistry and Cell Biology ◽

10.1007/bf00304312 ◽

1967 ◽

Vol 10 (4) ◽

pp. 305-308 ◽

Cited By ~ 13

Author(s):

T. Nagata ◽

O. Shibata ◽

T. Nawa

Keyword(s):

Tissue Culture ◽

Mitochondrial Dna ◽

Tritiated Thymidine ◽

Kidney Cells ◽

Liver And Kidney

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Antcin C fromAntrodia cinnamomeaProtects Liver Cells Against Free Radical-Induced Oxidative Stress and ApoptosisIn VitroandIn Vivothrough Nrf2-Dependent Mechanism

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/296082 ◽

2013 ◽

Vol 2013 ◽

pp. 1-17 ◽

Cited By ~ 26

Author(s):

M. Gokila Vani ◽

K. J. Senthil Kumar ◽

Jiunn-Wang Liao ◽

Shih-Chang Chien ◽

Jeng-Leun Mau ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Transcriptional Activation ◽

Liver Cells ◽

Ros Generation ◽

Antioxidant Genes ◽

Pi3k Activation ◽

Mice Liver ◽

Induced Apoptosis

In this study, we investigated the cytoprotective effects of antcin C, a steroid-like compound isolated from Antrodia cinnamaomea against AAPH-induced oxidative stress and apoptosis in human hepatic HepG2 cells. Pretreatment with antcin C significantly protects hepatic cells from AAPH-induced cell death through the inhibition of ROS generation. Furthermore, AAPH-induced lipid peroxidation, ALT/AST secretion and GSH depletion was significantly inhibited by antcin C. The antioxidant potential of antcin C was correlated with induction of antioxidant genes including, HO-1, NQO-1,γ-GCLC, and SODviatranscriptional activation of Nrf2. The Nrf2 activation by antcin C is mediated by JNK1/2 and PI3K activation, whereas pharmacologic inhibition of JNK1/2 and PI3K abolished antcin C-induced Nrf2 activity. In addition, AAPH-induced apoptosis was significantly inhibited by antcin C through the down-regulation of pro-apoptotic factors including, Bax, cytochrome c, capase 9, -4, -12, -3, and PARP.In vivostudies also show that antcin C significantly protected mice liver from AAPH-induced hepatic injury as evidenced by reduction in hepatic enzymes in circulation. Further, immunocytochemistry analyses showed that antcin C significantly increased HO-1 and Nrf2 expression in mice liver tissues. These results strongly suggest that antcin C could protect liver cells from oxidative stress and cell deathviaNrf2/ARE activation.

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Comparative Protective Effects of Spirulina and Spirulina Supplemented with Thiamineagainst Sub-acute Carbon Tetrachloride Toxicity in Rats

Biomedical & Pharmacology Journal ◽

10.13005/bpj/1670 ◽

2019 ◽

Vol 12 (2) ◽

pp. 511-526

Author(s):

Badr E. El-Bialy ◽

Neveen G. El-Boraey ◽

Ragaa A. Hamouda ◽

Mohamed M. Abdel-Daim

Keyword(s):

Body Weight ◽

Carbon Tetrachloride ◽

Spirulina Platensis ◽

Body Weight Gain ◽

Ros Generation ◽

Protective Effects ◽

Blood Indices ◽

Indirect Bilirubin ◽

Liver And Kidney ◽

Haemoglobin Content

Carbon tetrachloride (CCl4) is used extensively as an industrial solvent and considered the best-characterized experimental animal model of xenobiotic-induced hepatic toxicity via reactive oxygen species (ROS) generation. This study was designed to evaluate the protective effects of Spirulina platensis (SP) versus Spirulina platensis supplemented with thiamine (SPt) against subacute CCl4 toxicity in rats. Rats were divided into six equal groups; Control vehicle (0.5 ml/rat 1:1 olive oil in water), SP (800 mg/kg b.wt.), SPt (800 mg/kg b.wt.), CCl4 (1ml/kg b.wt.), SP + CCl4 and SPt + CCl4. All treatments were orally and daily for a month except CCl4 was given three times weekly. CCl4 caused significant reduction in body weight gain, haemoglobin content and haematocrit percentage accompanied by leukocytosis, granulocytosis, monocytosis and lymphocytopenia. Moreover, there were significant increase in the levels of serum ALT, AST; total, direct and indirect bilirubin; urea and creatinine of CCL4- intoxicated rats. CCL4- induced significant increase of malondialdehyde levels with significant reduction of catalase activity in liver and kidney. In addition, hepatic and renal various histopathological alterations were recorded. SP and SPt ameliorated almost these changes while they couldn’t reverse the reduction of body weight gains and red blood indices. The more potent effects on measured parameters were elucidated by SPt. In conclusion SP and SPt could be used as natural antioxidant supplements to counteract the CCl4 adverse effects.

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Chrysin protects mice liver and kidney from methandienone-induced oxi-dative ‎stress, inflammation a multi-biomarker approach

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v10i2.386 ◽

2019 ◽

Vol 10 (2) ◽

pp. 1081-1088

Author(s):

Marwah Y. Falih ◽

Abbas A. Mohammed ◽

Ghassan M. Sulaiman

Keyword(s):

Combined Treatment ◽

Serum Levels ◽

Hepatic Function ◽

Oxidation Activity ◽

Biochemical Effects ◽

Liver And Kidney ◽

Anti Oxidant ◽

Mice Liver ◽

Kidney Functions ◽

Renal Function Tests

Methandienone is a medication that has wide uses by competitors and young people in ‎gyms ‎for fitness. Chrysin (CR) is a characteristic natural flavonoid that has to incorporate ‎being a ‎cancer prevention agent, anti-inflammatory and anti-oxidant agent. Mus Musculus ‎mice ‎were therefore used in the current work to test the effects of methandienone on ‎vital ‎physiological functions as expressed by the liver, renal function tests and oxidation ‎activity. ‎The reverse effects of chrysin were also tested for the treatment of methandienone in ‎order ‎to determine the possibility of lowering levels of side effects. The results showed ‎clear ‎changes in biochemical effects on liver and kidney functions as a result of treatment ‎with ‎methandienone were also evident; The treated mice showed a significant elevation in ‎the ‎concentrations of serum levels of the hepatic function enzymes (ALP, AST, ALT) ‎and ‎kidney functions parameters (urea and creatinine).‎‏ ‏Combined treatment of mice ‎with ‎‎(methandienone + 25 mg/kg chrysin) caused a significant reduction in urea level ‎and ‎activities of ALP, ALT and AST (p<0.05) as compared to treatment with ‎methandienone ‎alone. Treatment with (methandienone + 50 mg/kg chrysin) also resulted in ‎a significant ‎decrease in the renal level and ALP and AST activities as compared to methandienone- ‎treated ‎mice. The present study concludes that methandienone causes damages to the liver ‎and the ‎kidney, as indicated by elevated levels of their functional enzymes. This effect ‎indicates ‎it increases oxidative stress in these organs, possibly due to elevated production of ‎free ‎radicals.

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The Effect of Papaya (Carica papaya L.) Leaf Extract to the Number of Trypanosoma evansi Steel in Liver and Kidney of Mice (Mus musculus L. 1758)

KnE Life Sciences ◽

10.18502/kls.v3i4.715 ◽

2017 ◽

Vol 3 (4) ◽

pp. 275

Author(s):

Yudi Yahya ◽

Anni Nurliani ◽

Heri Budi Santoso

Keyword(s):

Carica Papaya ◽

Degenerative Change ◽

Ethanolic Extract ◽

Trypanosoma Evansi ◽

Cellular Infiltration ◽

Vacuolar Degeneration ◽

Cytological Smear ◽

Liver And Kidney ◽

Mice Liver ◽

Kidney Liver

The purpose of this study proved the activity of the ethanolic extract of papaya leaf as anti-trypanosomiasis agent, determined the dose of extract which having an effect in inhibiting growth of T. evansi, and evaluated the histopathology of liver and kidney infected by Trypanosoma evansi Steel. Male Balb-c mice were infected by 3 × 107 T. evansi isolates. The native method was used to determine the level of parasitemia.The preparation was made using cytological smear method and paraffin method. The results showed that ethanolic extract of papaya leaf decreased the number of T. evansi. Ethanolic extract of papaya leaf at a dose of 300 mg · kg–1 BW is the most influential dose to reduce the number of T. evansi in liver and kidney of mice. Liver reveals degenerative change varying such as congestion, lipid degeneration, vacuolar degeneration, necrosis, and cellular infiltration. Kidney reveals tubular degeneration, necrosis, cellular infiltration, and glomerulonephritis. Keywords: Carica papaya L.; kidney; liver; mice; Trypanosoma evansi Steel

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Accumulation of cadmium in organs of experimental animals and its effect on the content of essential elements in the chronic intoxication

Hygiene and Sanitation ◽

10.47470/0016-9900-2021-100-11-1303-1309 ◽

2021 ◽

Vol 100 (11) ◽

pp. 1303-1309

Author(s):

Anna S. Fazlieva ◽

Denis O. Karimov ◽

Rustem A. Daukaev ◽

Mihail V. Kurilov ◽

Munira M. Ziatdinova ◽

...

Keyword(s):

Cadmium Chloride ◽

Cadmium Concentration ◽

Absorption Spectrometry ◽

Essential Elements ◽

Control Group ◽

Biological Processes ◽

Experimental Animals ◽

Blood Cadmium ◽

Liver And Kidney ◽

The Impact

Introduction. This article presents the results of studying the effects of cadmium chloride and its accumulation in experimental animals’ liver, kidneys, and blood. The impact of cadmium consumption on basic bioelements (zinc, copper, calcium) in organs was assessed. Materials and methods. Experimental groups of white outbred rats were exposed daily for three months to a cadmium chloride solution containing 1, 10 and 100 μg of cadmium. Cadmium exposure was assessed at 1, 4, 12, 30, 60 and 90 days. The concentrations of cadmium, calcium, copper and zinc were measured by atomic absorption spectrometry. Results. Whole blood cadmium concentration was not statistically different from the control group. The accumulation of cadmium in the blood was observed only after three months of exposure to a dose of 100 μg. The accumulation of cadmium in the liver occurred after one and two months of intoxication, depending on the dose. In the kidneys, an increase in cadmium occurred in all experimental groups after one month of injection. The metal content depended on the level of exposure, but no difference was observed between the liver and kidney. The concentration of zinc and calcium decreased in the kidneys and liver. Conclusion. Changes in calcium and zinc, accompanied by elevated levels of cadmium in the liver and kidneys, suggest that cadmium may interfere with the biological processes in which these elements are involved.

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