Radiosensitization by fullerene-C60 dissolved in squalene on human malignant melanoma through lipid peroxidation and enhanced mitochondrial membrane potential

2014 ◽  
Vol 97 ◽  
pp. 134-141 ◽  
Author(s):  
Shinya Kato ◽  
Masatsugu Kimura ◽  
Nobuhiko Miwa
2012 ◽  
Vol 77 (7) ◽  
pp. 1280-1289 ◽  
Author(s):  
B. Macías García ◽  
C. Ortega Ferrusola ◽  
I.M. Aparicio ◽  
A. Miró-Morán ◽  
A. Morillo Rodriguez ◽  
...  

2006 ◽  
Vol 290 (4) ◽  
pp. G674-G684 ◽  
Author(s):  
Defeng Wu ◽  
Arthur I. Cederbaum

S-adenosyl-l-methionine (SAMe) is protective against a variety of hepatotoxins, including ethanol. The ability of SAMe to protect against cytochrome P-450 2E1 (CYP2E1)-dependent toxicity was studied in hepatocytes from pyrazole-treated rats and HepG2 E47 cells, both of which actively express CYP2E1. Toxicity was initiated by the addition of arachidonic acid (AA) or by depletion of glutathione after treatment with l-buthionine sulfoximine (BSO). In pyrazole hepatocytes, SAMe (0.25–1 mM) protected against AA but not BSO toxicity. SAMe elevated GSH levels, thus preventing the decline in GSH caused by AA, and SAMe prevented AA-induced lipid peroxidation. SAMe analogs such as methionine or S-adenosyl homocysteine, which elevate GSH, also protected against AA toxicity. 5′-Methylthioadenosine (MTA), which cannot produce GSH, did not protect. The toxicity of BSO was not prevented by SAMe and the analogs because GSH cannot be synthesized. In contrast, in E47 cells, SAMe and MTA but not methionine or S-adenosyl homocysteine potentiated AA and BSO toxicity. Antioxidants such as trolox or N-acetyl cysteine prevented this synergistic toxicity of SAMe plus AA or SAMe plus BSO, respectively. In pyrazole hepatocytes, SAMe prevented the decline in mitochondrial membrane potential produced by AA, whereas in E47 cells, SAMe potentiated the decline in mitochondrial membrane potential. In E47 cells, but not pyrazole hepatocytes, the combination of SAMe plus BSO lowered levels of the antioxidant transcription factor Nrf2. Because SAMe can be metabolized enzymatically or spontaneously to MTA, MTA may play a role in the potentiation of AA and BSO toxicity by SAMe, but the exact mechanisms require further investigation. In conclusion, contrasting effects of SAMe on CYP2E1 toxicity were observed in pyrazole hepatocytes and E47 cells. In hepatocytes, SAMe protects against CYP2E1 toxicity by a mechanism involving maintaining or elevating GSH levels.


2010 ◽  
Vol 106 (1/2) ◽  
Author(s):  
Alisa Phulukdaree ◽  
Devapregasan Moodley ◽  
Anil A. Chuturgoon

Sutherlandia frutescens (SF), a medicinal plant indigenous to South Africa, is traditionally used to treat a diverse range of illnesses, including cancer and viral infections. The biologically active compounds of SF are polar, thus renal elimination increases susceptibility to toxicity in that organ. This study investigated the antioxidant potential, lipid peroxidation, mitochondrial membrane potential and apoptotic induction by SF extracts on proximal and distal tubule epithelial cells. Cell viability was determined using the MTT assay. Mitochondrial membrane potential was determined using a flow cytometric JC-1 Mitoscreen assay. Cellular glutathione and apoptosis were measured using the GSH-Glo™ Glutathione assay and Caspase-Glo® 3/7 assay, respectively. The IC50 values from the cell viability results for LLC-PK1 and MDBK were 15 mg/mL and 7 mg/mL, respectively. SF extracts significantly decreased intracellular glutathione in LLC-PK1 (p less than 0.0001) and MDBK (p less than 0.0001) cells, while lipid peroxidation increased in treated LLC-PK1 (p less than 0.0001) and MDBK (p less than 0.0001) cells. JC-1 analysis showed that SF extracts promoted mitochondrial membrane depolarization in both LLC-PK1 and MDBK cells by up to 80% (p less than 0.0001). The activity of caspase 3/7 increased in both LLC-PK1 (11.9-fold; p less than 0.0001) and MDBK (2.2-fold; p less than 0.0001) cells. SF extracts at high concentrations appear to increase oxidative stress, to alter mitochondrial membrane integrity, and to promote apoptosis in renal tubule epithelia.


Reproduction ◽  
2009 ◽  
Vol 138 (1) ◽  
pp. 55-63 ◽  
Author(s):  
C Ortega Ferrusola ◽  
L González Fernández ◽  
J M Morrell ◽  
C Salazar Sandoval ◽  
B Macías García ◽  
...  

Lipid peroxidation (LPO) of stallion spermatozoa was assessed in fresh semen and in samples of the same ejaculates after freezing and thawing. Particular attention was paid to individual differences in the susceptibility to LPO and its possible relationship with freezability. Innate levels of LPO were very low in fresh spermatozoa but increased after thawing, a change that was largely stallion-dependent. The level of LPO in fresh spermatozoa was not correlated with that of the thawed spermatozoa. Negative correlations existed between LPO and intact membranes post-thaw (r=−0.789, P<0.001), and also between LPO and spermatozoa with high mitochondrial membrane potential (Δψm) post-thaw (r=−0.689, P<0.001). LPO was also highly and significantly correlated with caspase activity. The correlation between caspase activity in ethidium positive cells and LPO was r=0.772, P<0.001. This LPO is unlikely to represent, per se, a sign of cryopreservation-induced injury, but it is apparently capable of triggering ‘apoptotic-like changes’ that could result in the sub-lethal cryodamage often seen among surviving spermatozoa.


Reproduction ◽  
2020 ◽  
Vol 160 (5) ◽  
pp. 783-792
Author(s):  
Maria S Ferrer ◽  
Roberto Palomares ◽  
David Hurley ◽  
Anna-Claire Bullington ◽  
Alejandro Hoyos-Jaramillo ◽  
...  

Bovine antisperm antibodies (ASAs) have been associated with teratospermia and asthenospermia. It was hypothesized here that scrotal insulation induces the formation of ASAs and deterioration of sperm function. Scrotal insulation bags were placed in 10 bulls for 8 days. Semen was collected on days −29, −22 and −2, twice weekly from days 5 to 54, and thereafter weekly until day 96 (day 0 = first day of scrotal insulation). On each collection day, scrotal circumference, sperm motility, morphology, membrane integrity, acrosome integrity, apoptosis, lipid peroxidation, mitochondrial membrane potential, ASA binding and DNA integrity were evaluated. The percentage of IgG- and IgA-bound sperm increased between days 12 and 96 (P < 0.0001), in association with poor motility (days 19–30, P < 0.005) and morphology (days 8–40, P < 0.0001). Mean scrotal circumference decreased between days 15 and 75 (P < 0.0001). There was also a deterioration in sperm membrane integrity (days 19–40, P < 0.0001), acrosome integrity (days 26–89, P < 0.0001), lipid peroxidation (days 5–12, P < 0.0001), and mitochondrial membrane potential (days 12–96, P = 0.001). In contrast, a decrease in apoptotic cells (days 37–83, P = 0.0002) and lipid peroxidation (days 19–96, P < 0.0001) was noticed. Most bulls recovered normospermia by day 96. However, the persistence of ASAs, acrosomal damage and dysfunctional mitochondria suggest a long term effect of scrotal insulation on sperm function and the homeostasis of the reproductive immune system.


2020 ◽  
Vol 11 (4) ◽  
pp. 6250-6255
Author(s):  
Poongodi T ◽  
Nazeema T H

The Polyherbal formulations are used as a potential target for treating various diseases due to its wide array of phytoconstituents with antioxidant potential. In the present study, the therapeutic effect of Polyherbal formulation (MKA) comprising of three plants Mimusops elengi L., Kedrostis foetidissima (Jacq.) Cogn. and Artemisia vulgaris L. were studied in LPS induced RAW 264.7 macrophages. Four different concentrations (25, 50, 75 and 100 µg/ml) of MKA were tested against control, LPS treatment and standard Quercetin in LPS induced RAW 264.7 macrophage cells. The rate of Lipid peroxidation was measured in terms of Malondialdehyde (MDA) levels. The cytosolic LDH leakage was determined by measuring NADH release at 340nm. The changes in mitochondrial membrane potential were studied by measuring red/green fluorescent intensity of JC-1 stained cells in the flow cytometer. It was found that MKA treatments significantly reduced the rate of Lipid peroxidation and LDH leakage compared to LPS treatment. The results of flow cytometry revealed that the JC-1 green fluorescent intensity decreased with increase in MKA concentration, in a dose-dependent manner. It is evident from the study results that, the MKA has a therapeutic effect on LPS induced RAW 264.7 macrophages by protecting the cells from lipid peroxidation, restoring the cell membrane integrity and mitochondrial membrane potential.


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