The Impact of the Combined Administration of 1MeTIQ and MK-801 on Cell Viability, Oxidative Stress Markers, and Glutamate Release in the Rat Hippocampus

AbstractMK-801, as an N-methyl-D-aspartate (NMDA) receptor inhibitor, causes elevation in glutamate release, which may lead to an increase in excitotoxicity, oxidative stress and, consequently, cell death. 1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) shows antioxidant activity. The aim of the present study was to evaluate the effect of combined treatment with 1MeTIQ and MK-801 on cell viability, antioxidant enzyme activity, and glutamate release in the rat hippocampus. Cytotoxicity was measured using lactate dehydrogenase leakage assay (LDH) and the methyl tetrazolium (MTT) assay; antioxidant enzyme activity (glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT)) were measured by ELISA kits. The release of glutamate in the rat hippocampus was measured using in vivo microdialysis methodology. An in vitro study showed that MK-801 induced cell death in a concentration-dependent manner and that 1MeTIQ partially reduced this adverse effect of MK-801. An ex vivo study indicated that MK-801 produced an increase in antioxidant enzyme activity (GPx, GR, and SOD), whereas coadministration of MK-801 and 1MeTIQ restored the activity of these enzymes to the control level. An in vivo microdialysis study demonstrated that combined treatment with both drugs decreased the release of glutamate in the rat hippocampus. The above results revealed that 1MeTIQ shows limited neuroprotective activity under conditions of glutamate-induced neurotoxicity.

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Determination of Oxidative Stress and Antioxidant Enzyme Activity for Physiological Phenotyping During Heavy Metal Exposure

Environmental Toxicology and Toxicogenomics - Methods in Molecular Biology ◽

10.1007/978-1-0716-1514-0_17 ◽

2021 ◽

pp. 241-249

Author(s):

Samrana Zahir ◽

Fan Zhang ◽

Jinhong Chen ◽

Shuijin Zhu

Keyword(s):

Oxidative Stress ◽

Heavy Metal ◽

Enzyme Activity ◽

Antioxidant Enzyme ◽

Antioxidant Enzyme Activity ◽

Metal Exposure ◽

Heavy Metal Exposure

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Curcumin Acts as a Chemosensitizer for Leiomyosarcoma Cells In Vitro But Fails to Mediate Antioxidant Enzyme Activity in Cisplatin-Induced Experimental Nephrotoxicity in Rats

Integrative Cancer Therapies ◽

10.1177/1534735419872811 ◽

2019 ◽

Vol 18 ◽

pp. 153473541987281 ◽

Cited By ~ 1

Author(s):

Irida Dhima ◽

Stelios Zerikiotis ◽

Panagiotis Lekkas ◽

Yannis V. Simos ◽

Maria Gkiouli ◽

...

Keyword(s):

Oxidative Stress ◽

Enzyme Activity ◽

Side Effects ◽

Antioxidant Enzyme ◽

Mitochondrial Function ◽

Intraperitoneal Administration ◽

Relative Weight ◽

Antioxidant Enzyme Activity ◽

Dose Finding ◽

In Vivo Model

Background. Cisplatin (cis-diamminedichloroplatinum) is a widely used chemotherapeutic agent for the treatment of various cancers. Although it represents an effective regimen, its application is accompanied by side effects to normal tissues, especially to the kidneys. Cisplatin generates free radicals and impairs the function of antioxidant enzymes. Modulation of cisplatin-induced oxidative stress by specific antioxidant molecules represents an attractive approach to minimize side effects. Methods. We studied the ability of curcumin to sensitize leiomyosarcoma (LMS) cells to cisplatin. Assays for cell proliferation, mitochondrial function, induction of apoptosis, and cell cycle arrest were performed using various concentrations of cisplatin and a concentration of curcumin that caused a nonsignificant reduction in cell viability. Moreover, the effect of curcumin was examined against cisplatin-induced experimental nephrotoxicity. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen (BUN), and the kidney’s relative weight. Oxidative stress was measured by means of enzymatic activities of superoxide dismutase and glutathione peroxidase in the rats’ blood and malondialdehyde levels in rats’ urine. Results. In our study, we found that curcumin sensitizes LMS cells to cisplatin by enhancing apoptosis and impairing mitochondrial function. In an in vivo model of cisplatin-induced experimental nephrotoxicity, intraperitoneal administration of curcumin failed to preserve blood’s antioxidant enzyme activity and decrease lipid peroxidation. Nevertheless, curcumin was able to protect nephrons’ histology from cisplatin’s toxic effect. Conclusion. Our results showed that curcumin can act as chemosensitizer, but its role as an adjunctive cisplatin-induced oxidative stress inhibitor requires further dose-finding studies to maximize the effectiveness of chemotherapy.

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Antioxidant Enzyme Activity and Oxidative Stress in Bovine Oocyte In Vitro Maturation

IUBMB Life ◽

10.1080/15216540152035073 ◽

2001 ◽

Vol 51 (1) ◽

pp. 57-64 ◽

Cited By ~ 85

Author(s):

P. D. Cetica ◽

L. N. Pintos ◽

G. C. Dalvit ◽

M. T. Beconi

Keyword(s):

Oxidative Stress ◽

Enzyme Activity ◽

Antioxidant Enzyme ◽

In Vitro Maturation ◽

Antioxidant Enzyme Activity ◽

Bovine Oocyte ◽

And Oxidative Stress

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Effect of Oxidative Stress on Lymphocytes from Elderly Subjects

Clinical Science ◽

10.1042/cs0940447 ◽

1998 ◽

Vol 94 (4) ◽

pp. 447-452 ◽

Cited By ~ 11

Author(s):

E. García-Arumí ◽

A. L. Andreu ◽

J. López-Hellín ◽

S. Schwartz

Keyword(s):

Oxidative Stress ◽

Enzyme Activity ◽

Oxidative Damage ◽

Antioxidant Enzyme ◽

Antioxidant Enzyme Activity ◽

Elderly Subjects ◽

Antioxidant Enzyme Activities ◽

Antioxidant Defences ◽

Protein Carbonyl Content ◽

Healthy Elderly

1. Oxidative damage has been associated with ageing, but there is no agreement as to whether or not it is produced by a decrease in antioxidant defences with the ageing process. In purified lymphocytes from 47 healthy elderly (75.27 ± 0.91 years) and 47 healthy young (29.87 ± 0.53 years) volunteers, we studied the levels of antioxidant enzyme activity (superoxide dismutase, catalase and glutathione peroxidase), protein oxidative damage (as protein carbonyl content) and lysosomal proteolytic activity (cathepsins B, H and L), with and without exposure to oxidative stress produced by 25 μmol/l H2O2. 2. There were no differences in antioxidant enzyme activities in the stressed and non-stressed samples between the young and elderly subjects, indicating that there was no relationship between age and antioxidant enzyme activity even in oxidative stress. However, a dissimilar response to oxidative stress was observed in protein oxidative damage and cathepsin B and L activities, depending on the age of the donor. 3. With these results we conclude that oxidative stress produces greater protein oxidative damage and increased protein degradation in elderly subjects than in young ones; this effect cannot be attributed to dissimilar antioxidant enzyme responses to oxidative stress, since these did not differ between the two age groups.

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