The Selective Cytotoxicity of γ-Linolenic Acid (GLA) is Associated with Increased Oxidative Stress

Author(s):  
Sujata Vartak ◽  
Mike E. C. Robbins ◽  
Arthur A. Spector
2011 ◽  
Vol 108 (6) ◽  
pp. 974-983 ◽  
Author(s):  
Siddhartha S. Saha ◽  
Mahua Ghosh

The present study was undertaken to evaluate the effect of α-eleostearic acid and punicic acid, two isomers of conjugated linolenic acid (CLnA) present in bitter gourd (Momordica charantia) and snake gourd oil (Trichosanthes anguina), respectively, against oxidative stress, inflammatory challenge and aberration in erythrocyte morphology due to streptozotocin (STZ)-induced diabetes. Male albino rats were divided into four groups consisting of eight animals in each group. The first group served as control and diabetes was induced in rats in groups 2–4 by a single intraperitoneal injection of STZ. Moreover, rats in groups 3 and 4 were treated with 0·5 % of α-eleostearic acid and 0·5 % of punicic acid of the total lipid given, respectively, by oral administration once per d. After administration, CLnA isomers had significantly reduced oxidative stress, lipid peroxidation and restored antioxidant and pro-inflammatory enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, reduced glutathione, NO synthase level in pancreas, blood and erythrocyte lysate. The ferric reducing antioxidant power (FRAP) assay of plasma showed that CLnA treatment caused improvement in the FRAP value which was altered after STZ treatment due to an increased level of free radicals. Expression of inflammatory cytokines such as TNF-α and IL-6 in blood and expression of hepatic NF-κB (p65) increased significantly after STZ treatment due to increased inflammation which was restored with the administration of CLnA isomers. From the obtained results, it could be concluded that α-eleostearic acid and punicic acid showed potent antioxidant and anti-inflammatory activity with varying effectivity.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Bamigboye J. Taiwo ◽  
Temidayo D. Popoola ◽  
Fanie R. van Heerden ◽  
Amos A. Fatokun

ABSTRACT Background The leaf of Anacardium occidentale L. has been a component of many herbal recipes in South-Western Nigeria. The work reported herein, therefore, explored the phytochemical composition of this plant and the potential anti-cancer activity of an isolated chemical constituent. Methods Phytochemical methods (including chromatographic analysis) combined with spectroscopic and spectrometric analyses (IR, HRMS and NMR (1D and 2D)) were used to identify chemical constituents. Cytotoxic effects were determined using the MTT viability assay and bright-field imaging. Induction of oxidative stress was determined using the fluorescence-based 2′,7′-dichlorofluorescein diacetate (DCFDA) assay. Results For the first time in the plant, Compound 1 was isolated from the leaf extract and identified as pentagalloylglucose. Compound 1 was significantly cytotoxic against the cancer cell lines HeLa (human cervical adenocarcinoma cell line) and MRC5-SV2 (human foetal lung cancer cell line), with IC50 of 71.45 and 52.24 μg/ml, respectively. The selectivity index (SI) for Compound 1 was 1.61 (IC50 against the normal human foetal lung fibroblast cell line MRC-5 was 84.33μg/ml), demonstrating better cancer cell-selectivity compared to doxorubicin with a SI of 1.28. The cytotoxic activity of Compound 1 in HeLa cells was also rapid, as shown by its concentration- and time-dependent 3 h and 6 h cytotoxicity profiles, an effect not observed with doxorubicin. Generation of reactive oxygen species at high concentrations of pentagalloylglucose to induce oxidative stress in cancer cells was identified as a mechanistic event that led to or resulted from its cytotoxicity. Conclusions We suggest that pentagalloylglucose is selectively cytotoxic to cancer cells, and at high concentrations could exhibit pro-oxidant effects in those cells, as opposed to its general anti-oxidant effects in cells. Also, the presence of Compound 1 (pentagalloylglucose) in the plant and its cancer cell-selective cytotoxicity provide some rationale for the ethno-medicinal use of the plant’s leaf extract for treating diseases associated with excessive cell proliferation. Further studies are required to dissect the molecular mechanisms and players differentially regulating the biphasic anti-oxidant and pro-oxidant effects of pentagalloylglucose in normal and cancer cells.


2010 ◽  
Vol 140 (10) ◽  
pp. 1714-1721 ◽  
Author(s):  
Aktham Hassan ◽  
Ayman Ibrahim ◽  
Khaly Mbodji ◽  
Moïse Coëffier ◽  
Frédéric Ziegler ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Hao Han ◽  
Peipei Yan ◽  
Li Chen ◽  
Cheng Luo ◽  
Hui Gao ◽  
...  

Plant sterols (PS) have potential preventive function in atherosclerosis due to their cholesterol-lowering ability. Dietaryα-linolenic acid in flaxseed oil is associated with a reduction in cardiovascular events through its hypolipidemic and anti-inflammation properties. This study was designed to evaluate the effects of flaxseed oil containingα-linolenic acid ester of PS (ALA-PS) on atherosclerosis and investigate the underlying mechanisms. C57BL/6 mice were administered a regular diet and apoE knockout (apoE-KO) mice were given a high fat diet alone or supplemented with 5% flaxseed oil with or without 3.3% ALA-PS for 18 weeks. Results demonstrated that flaxseed oil containing ALA-PS was synergistically interaction in ameliorating atherosclerosis as well as optimizing overall lipid levels, inhibiting inflammation and reducing oxidative stress. These data were associated with the modification effects on expression levels of genes involved in lipid metabolism (PPARα, HMGCR, and SREBPs), inflammation (IL-6, TNF, MCP-1, and VCAM-1), and oxidative stress (NADPH oxidase).


Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 122
Author(s):  
David Ramiro-Cortijo ◽  
Ángel Luis López de Pablo ◽  
Mᵃ Rosario López-Giménez ◽  
Camilia R. Martin ◽  
Joanne Brown ◽  
...  

After birth, preterm infants are deficient in arachidonic acid (ARA), docosahexaenoic acid (DHA), and antioxidants, increasing their risk of oxidative stress-related pathologies. The principal aim was to evaluate if supplementation with long-chain polyunsaturated fatty acids (LCPUFAs) improves antioxidant defenses. In total, 21 preterm infants were supplemented with ARA and DHA in a 2:1 ratio (ARA:DHA-S) or with medium-chain triglycerides (MCT-S). Plasma n-3 and n-6 LCPUFAs were measured at birth, postnatal day 28, and 36 weeks of postmenstrual age (36 WPA) by gas chromatography–mass spectroscopy. Plasma antioxidants (glutathione (GSH), catalase, and thiols) and oxidative damage biomarkers (malondialdehyde (MDA), carbonyls) were analyzed at the same time points by spectrophotometry, and scores of antioxidant status (Antiox-S) and oxidative damage (Proxy-S) were calculated. At 36 WPA, linoleic acid (LA) and dihomo-γ-linolenic acid (DGLA) were decreased in ARA:DHA-S compared to the MCT-S group (LA: ARA:DHA-S = 18.54 ± 1.68, MCT-S = 22.80 ± 1.41; p = 0.018; DGLA: ARA:DHA-S = 1.68 ± 0.38, MCT-S = 2.32 ± 0.58; p = 0.018). Furthermore, α-linolenic acid (ALA) was increased in ARA:DHA-S (ARA:DHA-S = 0.52 ± 0.33, MCT-S = 0.22 ± 0.10; p = 0.018). Additionally, LA:DHA ratio was decreased in the ARA:DHA-S compared to control group (ARA:DHA-S = 6.26 ± 2.35, MCT-S = 8.21 ± 2.65; p = 0.045). By the end of supplementation (36 WPA), catalase, thiol groups, and Antiox-S were significantly higher in neonates receiving ARA:DHA-S compared to those receiving MCT-S, with no differences in oxidative stress biomarkers. In conclusion, ARA:DHA supplementation in preterm neonates resulted in an overall improvement in antioxidant to oxidant balance and a decrease in early fatty acid precursors of the n-6 relative to the n-3 pathway. These effects may reduce oxidative stress and inflammation.


2017 ◽  
Vol 117 (9) ◽  
pp. 1199-1211 ◽  
Author(s):  
Émilie Fortin ◽  
Richard Blouin ◽  
Jérôme Lapointe ◽  
Hélène V. Petit ◽  
Marie-France Palin

AbstractAlthough beneficial effects have been attributed to PUFA supplementation in high-yielding dairy cows, diets rich in PUFA may also increase oxidative stress in tissues such as the liver. To fully exploit the health benefits of PUFA, we believe that the addition of natural antioxidants could help in preventing oxidative damage. Using an in vitro precision-cut liver slices (PCLS) tissue culture system, we investigated the effects of different linoleic acid (LA, n-6):α-linolenic acid (ALA, n-3) ratios (LA:ALA ratio of 4, LA:ALA ratio of 15 and LA:ALA ratio of 25) in the presence or absence of the antioxidant enterolactone (ENL) on (1) the mRNA abundance of genes with key roles in hepatic lipid metabolism, oxidative stress response and inflammatory processes, (2) oxidative damages to lipids and proteins and (3) superoxide dismutase activity in early-lactating dairy cows. The addition of LA and ALA to PCLS culture media increased oxidative damage to lipids as suggested by higher concentrations of thiobarbituric acid reactive substances and increased the expression of nuclear factor erythroid 2-related factor 2 target genes. The addition of ENL was effective in preventing lipid peroxidation caused by LA and ALA. Transcript abundance of sterol regulatory element-binding transcription factor 1 and its lipogenic target genes acetyl-CoA carboxylase α, fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD) was decreased with LA and ALA, whereas ENL decreased FASN and SCD gene expression. Our results show that addition of LA and ALA to PCLS culture media lowers hepatic lipogenic gene expression and increases oxidative damages to lipids. On the other hand, addition of ENL prevents oxidative damages provoked by these PUFA.


1996 ◽  
Vol 271 (3) ◽  
pp. E471-E476 ◽  
Author(s):  
N. E. Cameron ◽  
M. A. Cotter

Nerve conduction and perfusion deficits in diabetic rats depend on increased oxidative stress and impaired n-6 essential fatty acid metabolism, which are corrected by free radical scavenger and gamma-linolenic acid (GLA)-rich oil treatments, respectively. We investigated the interaction between these mechanisms on conduction velocity and endoneurial blood flow by use of low-dose antioxidant (BM15.0639) and GLA treatments, alone and in combination. After 8 wk of streptozotocin-induced diabetes, sciatic motor conduction velocity was 20.9% reduced. Treatment with GLA or BM15.0639 for the final 2 wk corrected this deficit by 18.5 and 20.0%, respectively; however, joint treatment caused 71.5% improvement, corresponding to a 7.5-fold amplification of individual drug effects. A 48.3% deficit in sciatic nutritive endoneurial blood flow was corrected by 34.8 and 24.8% with GLA and BM15.0639 treatments, respectively. With joint treatment, the flow improvement of 72.5% was greater than expected from individual drug effects, indicating a facilitatory interaction. Thus the synergistic effect of combined antioxidant and n-6 essential fatty acid treatment could potentially provide increased therapeutic power against diabetic neuropathy.


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