Comparative Studies on Lipid Peroxidation in the Kidney of Rats, Mice, and Hamsters and on the Effect of Cysteine, Glutathione, and Diethyl Maleate Treatment on Mortality and Nephrotoxicity After Administration of Potassium Bromate

1987 ◽  
Vol 6 (4) ◽  
pp. 489-501 ◽  
Author(s):  
Y. Kurokawa ◽  
N. Takamura ◽  
C. Matsuoka ◽  
T. Imazawa ◽  
Y. Matsushima ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Potassium Bromate ◽  
Time Dependent ◽  
Dependent Manner ◽  
Diethyl Maleate ◽  
Protein Nitrogen ◽  
B6c3f1 Mice ◽  
Dose Dependent ◽  
F344 Rats ◽  
Male F344 Rats

As an index of lipid peroxidation (LPO), levels of thiobarbituric acid (TBA)-reactive substances were examined in the kidneys of male F344 rats, BDF1, CDF1, and B6C3F1 mice, and Syrian golden hamsters after a single intravenous (IV) administration of potassium bromate (KBrO3) at various doses. In the rats, LPO levels were significantly increased in both a dose-dependent and time-dependent manner. However, when the rats were given intraperitoneal (IP) injection of cysteine, the levels of LPO were not significantly different between KBrO3-treated animals and controls. In CDF1 mice, the slight increases in LPO levels observed were much weaker and not statistically significant. On the other hand, treatment of BDF1 and B6C3F1 mice or hamsters with KBrO3 resulted in decreased values as compared to controls. The effect of treatment with cysteine, glutathione (GSH), or diethyl maleate (DEM) on mortality was tested in male F344 rats given IV injection of KBrO3 at various doses. Significant reduction and elevation in the mortality were observed in rats treated with cysteine or GSH and DEM, respectively. Significant dose-dependent and time-dependent increases were observed in the levels of serum non-protein nitrogen (NPN), blood urea nitrogen (BUN), and creatinine, and absolute and relative weight of the kidneys in male F344 rats administered KBrO3 IV. Microscopically, the appearance of numerous eosinophilic droplets in the cytoplasm of proximal tubular epithelium of KBrO3-treated rats was noteworthy. All these changes were reduced and exacerbated by treatment with cysteine or GSH and DEM, respectively. The possibility of LPO formation in the kidney by active oxygen radicals generated by KBrO3 is suggested. A possible relationship between LPO levels in the kidney and species differences in the renal toxicity and carcinogenicity of KBrO3 is implicated.

Dose-dependent enhancing effects of quinacrine on induction of preneoplastic glutathione S-transferase placental form positive liver cell foci in male F344 rats

1991 ◽  
Vol 12 (10) ◽  
pp. 1911-1915 ◽  
Author(s):  
Katsumi Imaida ◽  
Junichi Yoshida ◽  
Chikako Uneyama ◽  
Hiroyuki Ogasawara ◽  
Takayoshi Imazawa ◽  
...  
Keyword(s):  
Liver Cell ◽  
Glutathione S Transferase ◽  
Dose Dependent ◽  
F344 Rats ◽  
Male F344 Rats

scholarly journals Preclinical Study on the Ameliorating Effect of L-Ascorbic Acid for the Oxidative Stress of Caused by Chronic Administration of Organic Nitrates in Cardiovascular Diseases

2021 ◽  
Author(s):  
Ahmed M Hamdan ◽  
Zuhair M. Mohammedsaleh ◽  
Aalaa Aboelnour ◽  
Sherif M.H. Elkhannishi
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Chronic Administration ◽  
Stress Factors ◽  
Male Rats ◽  
Oxidative Stress Marker ◽  
Organic Nitrates ◽  
Dependent Manner ◽  
Dose Dependent

Abstract PurposeThe therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid peroxidation inside the red blood cells (RBCs) occur. The principal objective of our research is to explain the ameliorating effect of L-ascorbic acid for the deleterious effects of chronic administration of nitrovasodilator drugs. MethodsWe studied some biochemical parameters for the oxidative stress using groups of high sucrose/fat (HSF) diet Wistar male rats chronically orally administered ISMN. Afterwards, we evaluated the role of L-ascorbic acid against these biochemical changes. ResultsChronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation, hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation, the cellular levels of pro-inflammatory cytokines marker (NF-κB) and apoptosis markers (caspase-3) in myocardium muscles in a dose dependent manner. Meanwhile, such exposure caused decline in the enzymatic effect of superoxide dismutase (SOD), glutathione (GSH) and catalase activity (CAT) accompanied with a decrease of in the level of mitochondrial oxidative stress marker (nrf2) in myocardium muscles and decrease in the serum iron and total iron binding capacity (TIBC) in a dose dependent manner. Concomitant treatment with L-ascorbic acid significantly diminished these changes for all examined parameters.ConclusionChronic administration of organic nitrates leads to the alteration of the level of oxidative stress factors in the myocardium tissue due to generation of reactive oxygen species. Using vitamin C can effectively ameliorate such intoxication to overcome the nitrate tolerance.

scholarly journals Dose-Dependent Renal Tubular Toxicity of Harman and Norharman in Male F344 Rats

1992 ◽  
Vol 20 (2) ◽  
pp. 197-204 ◽  
Author(s):  
Akihiro Hagiwara ◽  
Emiko Asakawa ◽  
Yasushi Kurata ◽  
Masashi Sano ◽  
Masao Hirose ◽  
...  
Keyword(s):  
Tubular Toxicity ◽  
Renal Tubular ◽  
Dose Dependent ◽  
F344 Rats ◽  
Male F344 Rats

Protective Role of Raphanus Sativus Root Extract on Paracetamol-Induced Hepatotoxicity in Albino Rats

2007 ◽  
Vol 77 (1) ◽  
pp. 41-45 ◽  
Author(s):  
Chaturvedi ◽  
George ◽  
Machacha
Keyword(s):  
Lipid Peroxidation ◽  
Raphanus Sativus ◽  
Thiobarbituric Acid ◽  
Protective Role ◽  
Albino Rats ◽  
Root Extract ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Serum Glutamate

The methanol extract of Raphanus sativus root extract showed a protective effect on paracetamol-induced hepatotoxicity in a dose-dependent manner. Degree of lipid peroxidation caused by paracetamol was measured in terms of thiobarbituric acid reactive substances (TBARS) and protection was measured in reference to serum glutamate oxaloacetate transaminase (SGOT), serum glutamate aspartate transaminase (SGPT), and blood and hepatic levels of antioxidants like glutathione and catalase. Administration of extract along with paracetamol showed significant protection. Levels of TBARS were found to be low, activities of SGOT and SGPT were low, while hepatic glutathione levels were significantly higher in experimental rats that received the mixture of paracetamol and the extract as compared to rats that received paracetamol only. Activities of catalase were also high in all experimental groups. Thus this study indicates the involvement of Raphanus sativus root extract with antioxidants like glutathione and catalase in rendering protection against paracetamol-induced lipid peroxidation and hepatotoxicity.

In vitro inhibition of phosphodiesterase-5 and arginase activities from rat penile tissue by two Nigerian herbs (Hunteria umbellata and Anogeissus leiocarpus)

2017 ◽  
Vol 28 (4) ◽  
Author(s):  
Ganiyu Oboh ◽  
Adeniyi Abiodun Adebayo ◽  
Ayokunle Olubode Ademosun ◽  
Aline August Boligon
Keyword(s):  
Lipid Peroxidation ◽  
Dependent Manner ◽  
Inhibitory Property ◽  
In Vitro Inhibition ◽  
Anogeissus Leiocarpus ◽  
Dose Dependent ◽  
Phosphodiesterase 5

AbstractBackground:andMethods:The effects of the extracts on important enzymes (PDE-5 and arginase) linked with ED and pro-oxidants (FeResults:The results showed that both extracts inhibited PDE-5 and arginase activities in a dose-dependent manner. Inhibitory property ofConclusions:The ability of the extracts to inhibit PDE-5, arginase and pro-oxidant induced lipid peroxidation, and chelate metal might suggest their folkloric use for the management of ED.

Study on Mechanisms of Telomerase Regulation in Arsenic Trioxide Inducing Apoptosis in Myelodysplasia Cell Line.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4706-4706
Author(s):  
Hongyan Tong ◽  
Jie Jin ◽  
Weilai Xu ◽  
Wenbin Qian ◽  
Maofang Lin
Keyword(s):  
Mrna Expression ◽  
Cell Line ◽  
Telomerase Activity ◽  
Time Dependent ◽  
Dependent Manner ◽  
Htert Gene ◽  
Binding Factor ◽  
Telomerase Regulation ◽  
Dose Dependent ◽  
Ttaggg Repeat

Abstract The telomerase activity can be down regulated by arsenic trioxide (As2O3), which is regarded as an apoptotic induction agent, is confirmed in many kinds of tumor cells. To investigate the mechanisms of telomerase regulation and to explore the correlation of As2O3 inducing apoptosis and telomerase regulation in MUTZ-1 cells, which are established as a high-risk myelodysplasia Cell line that derived from a MDS patient (FAB subtype refractory anemia with excess of blasts), a quantitative assessment of the telomerase activity by TRAP-ELISA and detection of the expression levels of hTERT, TRF1 (TTAGGG repeat binding factor 1), TRF2 (TTAGGG repeat binding factor 2), bcl-2, bax mRNA were performed, together with the assessment of the apoptosis by means of translocation of phosphatidylserine (PS) through flow cytometry assay. The results indicated that a typical apoptotic cell group distribution of DNA content was represented in the MUTZ-1 cells after being exposed to As2O3 at the range of concentration from 1μmol/L to 8μmol/L in a dose-dependent manner (r=0.736, P<0.001) and time-dependent manner (r=0.674, p<0.05), and the telomerase activity was down-regulated in a time-dependent manner (r=−0.976,P=0.024), and the expression level of hTERT mRNA in MUTZ-1 cells was represented in a dose-dependent manner (r=−0.892,P=0.042) and time-dependent manner (r=−1.000,P=0.04), after the cells were treated by As2O3 at the dosage as above. It was showed that a significant correlation between the decreased telomerase activity and the increased percentage of apoptotic cells in the treated cells (r=0.938,P=0.018), and there was a strong relationship between the telomerase activity and the mRNA expression of hTERT gene (r=0.783,P=0.022). However, As2O3 has no obvious effect on the expression level of TRF1 mRNA and TRF2 mRNA, which were regarded as two telomere-binding proteins. Further findings indicated that the inhibition of telomerase activity in MUTZ-1 cells was accompanied with down-regulated mRNA expression of bcl-2 gene (densitometry readings: 0.255±0.017 vs 0.466±0.069, P<0.05) and decreased ration of bcl-2/bax (densitometry reading ratios: 0.890±0.083 vs 0.546±0.014, P<0.05) at the dosage of 4μmol/L for 24 hours. These observations suggest that the apoptosis induced by As2O3 on MUTZ- 1 cells might be mediated through the inhibition of telomerase activity regulated by expression of hTERT gene, which implies that may be one of the mechanisms of As2O3 inducing apoptosis in MUTZ-1 cells.

Hormone-Conditional Activation of Bcr-Abl Kinase Highlights Stat5 Anti-Apoptotic Pathway Prior to Promoting Cell Growth.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3380-3380
Author(s):  
Ratanakanit Harnprasopwat ◽  
Naoyuki Takahashi ◽  
Seiichiro Kobayashi ◽  
Kazuaki Yokoyama ◽  
Kiyoko Izawa ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Time Dependent ◽  
Viable Cell Number ◽  
Dependent Manner ◽  
Comparable Rate ◽  
Gm Csf ◽  
Abl Kinase ◽  
C Terminus ◽  
Custom Made ◽  
Dose Dependent

Abstract Abstract 3380 Bcr-Abl protein elicits a diverse array of downstream signals and is responsible for development of Philadelphia chromosome (Ph)-positive leukemias. In this fusion protein, disruption or deletion of a N-terminal coiled-coil (CC) region of Bcr results in substantially decreased tyrosine kinase activity and defective cellular transformation, indicating the essential role of Abl oligomerization in its constitutive kinase activity. Fusion of the estrogen receptor (ER) ligand binding domain (LBD) to the C-terminus of Abl generates a ligand-activated tarnsforming version, while additional sequences in Bcr may also be required for oncogenic competence since Bcr-Abl mutants containing just the extreme CC region cannot transform fibroblasts. To revisit the mechanism of Bcr-Abl-induced leukemogenesis and especially to dissect early signaling events upon Bcr-Abl activation, we applied this fusion technology to construct p190DccER, a p190Bcr-Abl mutant including ER-LBD at the C-terminus but not CC region at the N-terminus. GM-CSF-dependent human TF-1 cells were virally transduced with p190DccER as well as wild-type p190 (WT), p190Dcc and vector control, respectively, and a series of transformants were subjected to biological assays as well as biochemical analysis During a few days after switch from GM-CSF to 4-HT, viable cell number of p190DccER-transformed TF-1 cells was not increased but maintained, and thereafter proliferated at the comparable rate to GM-CSF-supported cells. Their growth was dose-dependent on 4-HT unless not more than 1.0mM. The effect of 4-HT on TF-1/p190DccER cells was easily canceled by imatinib in a dose-dependent manner. The profile of phosphotyrosine containing proteins quite resembled between 4-HT-treated TF-1/p190DccER cells and TF-1/p190WT cells. Unexpectedly, stable detection of autophosphorylated p190DccER required as long as several hours or beyond a day after 4-HT stimulation and so did phospho-CrkL. This can be explained by the observation that ligand-free p190DccER was highly unstable, and upon 4-HT binding, its stability increased in a time-dependent manner. Such a stabilizing mechanism might be adapted to substrate proteins including CrkL, which are directly bound to and phosphorylated by Bcr-Abl. On the contrary, 4-HT-induced tyrosine phosphorylation of Stat5 could be observed within 10min, suggesting its dominant role in the initial anti-apoptotic phase triggered by p190DccER. Next, we investigated gene expression profiling of TF-1/p190DccER cells using custom-made oligonucleotide DNA microarray and found a small number of genes differentially expressed before and after 4-HT treatment. Quantitative real-time polymerase chain reaction (QR-PCR) analysis confirmed that seven genes (BCL-XL, HIF-1A, HSPA1A, WT1, PRAME, BAG3 and GATA2) were significantly upregulated by 4-HT in a time-dependent manner. To identify Stat5 target genes among these candidates, we created a doxycycline (DOX)-inducible lentiviral expression system for constitutively active Stat5 mutant (mStat5A1*6). Then, selective activation of Stat5 in TF-1 cells resulted in suppression of apoptosis after GM-CSF withdrawal, and significantly upregulated five of seven candidate genes (BCL-XL, HIF-1A, HSPA1A, WT1, PRAME). These results suggest that the Bcr-Abl/Stat5 pathway is likely to integrate multiple effector molecules to prevent apoptosis, and that they are potential molecular targets in Ph-positive leukemias. The present experimental system helps us to perform functional dissection of signal transducers activated by Bcr-Abl kinase. Disclosures: No relevant conflicts of interest to declare.

3,3′,5′-Triiodothyronine inhibits ontogenetic development of iodothyronine-5′-deiodinase in the liver of the neonatal mouse

1988 ◽  
Vol 119 (2) ◽  
pp. 181-188 ◽  
Author(s):  
Doo Chol Han ◽  
Kanji Sato ◽  
Yuko Fujii ◽  
Minoru Ozawa ◽  
Hidehito Imamura ◽  
...  
Keyword(s):  
Single Injection ◽  
Inhibitory Effect ◽  
Antagonistic Effect ◽  
Time Dependent ◽  
Dependent Manner ◽  
Neonatal Mice ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Abstract. To elucidate the effect of rT3 on iodothyronine-5′-deiodinating activity (I-5′-DA) in the liver of neonatal mice, rT3 was injected sc on the 5–8th day after birth and I-5′-DA in the liver was determined. A single injection of rT3 (0.01–1 μg/g) inhibited the ontogenetically developing I-5′-DA in a dose- and time-dependent manner. The inhibitory effect was reversible and specific for I-5′-DA. Lineweaver-Burk analysis revealed that the time- and dose-dependent decrease in the enzyme activity was due to a decrease in Vmax with no alteration in Km values (5 × 10−8 mol/l). The maximal inhibitory effect was observed at a dose of 1 μg rT3/g, whereas the inhibitory effect was diminished at greater doses (4–10 μg/g), probably owing to a contamination with T4 of the rT3 preparation administered. Furthermore, consistent with our previous in vitro findings, rT3 inhibited the I-5′-DA induced by T3 in the liver of neonatal mice. These findings suggest that rT3 inhibited I-5′-DA in the liver of neonatal mice by decreasing the amount of enzyme available to the substrate and that rT3 also elicited an antagonistic effect against T3 in the induction of I-5′-DA in vivo.

Itraconazole and fluconazole-induced toxicity in rat hepatocytes: a comparativein vitro study

2002 ◽  
Vol 21 (1) ◽  
pp. 43-48 ◽  
Author(s):  
N Somchit ◽  
S M Hassim ◽  
S H Samsudin
Keyword(s):  
Cytochrome P450 ◽  
Lactate Dehydrogenase ◽  
Rat Hepatocytes ◽  
Antifungal Drugs ◽  
Vitro Study ◽  
Time Dependent ◽  
In Vitro Toxicity ◽  
Dependent Manner ◽  
Dose Dependent

This current study was to investigate the in vitrocytotoxicity of rat hepatocytes induced by the antifungal drugs, itraconazole and fluconazole. Both antifungal drugs caused dose-dependent cytotoxicity. In vitro incubation of hepatocytes with itraconazole revealed significantly higher lactate dehydrogenase (LDH) leakage when compared to fluconazole. Phenobarbital pretreated hepatocytes contained significantly higher total cytochrome P450 content than the control hepatocytes. P450 content was reduced approximately 30% for both types of hepatocytes after 6 hours incubation. Interestingly, cytotoxicity of itraconazole was reduced significantly by phenobarbital pretreatment. Phenobarbital did not have any effect on the cytotoxicity induced by fluconazole. These results demonstrate the in vitro toxicity of hepatocytes induced by itraconazole and fluconazole that were expressed in a dose and time-dependent manner. Phenobarbital plays a role in the cytoprotection of hepatocytes to itraconazole-induced but not fluconazole-induced cytotoxicity in vitro.

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