Omega-3 Polyunsaturated Fatty Acids' Effect on Markers of Oxidative Stress
Omega-3 Polyunsaturated Fatty Acids' Effect on Markers of Oxidative Stress
Background: The mechanisms of particulate matter (PM) -induced health effects are believed to involve inflammation and oxidative stress. Increased intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) appears to have anti-inflammatory effects.
Objective: As part of a trial to evaluate whether n-3 PUFA supplementation could protect against the cardiac alterations linked to PM exposure, we measured biomarkers of response to oxidative stimuli [copper/zinc (Cu/Zn) superoxide dismutase (SOD) activity, lipoperoxidation (LPO) products, and reduced glutathione (GSH) ] and evaluated the impact of supplementation on plasma levels.
Methods: We recruited residents from a nursing home in Mexico City chronically exposed to PM ≤ 2.5 µm in aerodynamic diameter (PM2.5) and followed them from 26 September 2001 to 10 April 2002. We randomly assigned subjects in a double-blind fashion to receive either fish oil (n-3 PUFA) or soy oil. We measured PM2.5 levels indoors at the nursing home, and measured Cu/Zn SOD activity, LPO products, and GSH at different times during presupplementation and supplementation phases.
Results: Supplementation with either fish or soy oil was related to an increase of Cu/Zn SOD activity and an increase in GSH plasma levels, whereas exposure to indoor PM2.5 levels was related to a decrease in Cu/Zn SOD activity and GSH plasma levels.
Conclusion: Supplementation with n-3 PUFA appeared to modulate the adverse effects of PM2.5 on these biomarkers, particularly in the fish oil group. Supplementation with n-3 PUFA could modulate oxidative response to PM2.5 exposure.
Environmental exposure to particulate matter (PM) has been associated with increased cardiovascular mortality in the elderly (Aga et al. 2003; Devlin et al. 2003; Samet et al. 2000) and reductions in heart rate variability (HRV), a measure of cardiac autonomic regulation (Gold et al. 2000; Holguin et al. 2003; Park et al. 2005). Although not well understood, the mechanisms of PM-induced health effects are believed to involve inflammation and oxidative stress initiated by the formation of reactive oxygen species (ROS) within affected cells (Cho et al. 2005; Gonzalez-Flecha 2004). In vitro studies have shown that inhaled PM causes expression of nuclear factor kappa-B (NF-κB)-related genes and oxidant-dependent NF-κB activation (Jimenez et al. 2000; Shukla et al. 2000). To defend against the oxidative damage, cells use up their stores of a key antioxidant, glutathione; glutathione depletion can induce a state of cellular stress and the activation of additional intracellular signaling cascades that regulate the expression of cytokine and chemokine genes and widespread proinflammatory effects remote from the site of damage (Saxon and Diaz-Sanchez 2005). Data from PM samples of 20 European cities have shown that PM with an aerodynamic diameter ≤ 2.5 µm (PM2.5) has strong redox activity and is able to deplete artificial respiratory lining fluid of reduced glutathione (GSH) and ascorbate (Künzli et al. 2006). PM, depending on its toxicity, seems also to inhibit protective enzymes involved in oxidative stress responses [copper/zinc (Cu/Zn) superoxide dismutase (SOD), manganese SOD, glutathione peroxidase (GSH-Px), and glutathione reductase] (Hatzis et al. 2006). Alteration of autonomic function related to PM2.5 exposure appears to be partly associated with oxidative stress (Brook et al. 2003; Chahine et al. 2007).
Increased intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) has been shown to decrease the risk of cardiovascular events (GISSI Prevenzione Investigators 1999; Kris-Etherton et al. 2002; Leaf et al. 2003). The protective effect of n-3 PUFA seems to be linked in part to its cardiac antiarrhythmic properties (Christensen et al. 2001; Holguin et al. 2005; Kris-Etherton et al. 2002; Leaf 2001) and its anti-inflammatory effects (Calder 2006). Long-chain n-3 PUFA appears to act both directly (by replacing arachidonic acid as an eicosanoid substrate and inhibiting arachidonic acid metabolism) and indirectly by altering the expression of inflammatory genes through effects on transcription factor activation (Calder 2006). Fish oil has been shown to modulate endothelial activation possibly by reducing ROS and therefore leading to the subsequent inactivation of the NF-κB system of gene transcription. This role of oxygen scavenging would lead to the prevention of O2-generating hydrogen peroxide (H2O2) and thus prevent cell activation (De Caterina et al. 2000).
We have previously shown that exposure to PM2.5 is related to a decrease in HRV in elderly residents of a nursing home in Mexico City (Holguin et al. 2003) and that fish oil supplementation could increase HRV (Holguin et al. 2005) and modulate the adverse effects of PM2.5 on HRV (Romieu et al. 2005). We hypothesized that one of the mechanisms by which fish oil and, to a lesser extent, soy oil supplementation would modulate the adverse effects of PM2.5 on HRV would be by acting on the oxidative stress response, reducing the generation of ROS, modulating the use of GSH as part of the oxidative stress response, and increasing the activity of enzymes involved in response to oxidative stimuli. We tested this hypothesis in a randomized trial of fish oil versus soy oil supplementation to prevent reductions in cardiac autonomic function associated with PM exposure. During the trial, we measured Cu/Zn SOD activity, GSH, and LPO levels in plasma to evaluate the impact of fish oil and soy oil supplementation and exposure to PM2.5 on these biomarkers.
Background: The mechanisms of particulate matter (PM) -induced health effects are believed to involve inflammation and oxidative stress. Increased intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) appears to have anti-inflammatory effects.
Objective: As part of a trial to evaluate whether n-3 PUFA supplementation could protect against the cardiac alterations linked to PM exposure, we measured biomarkers of response to oxidative stimuli [copper/zinc (Cu/Zn) superoxide dismutase (SOD) activity, lipoperoxidation (LPO) products, and reduced glutathione (GSH) ] and evaluated the impact of supplementation on plasma levels.
Methods: We recruited residents from a nursing home in Mexico City chronically exposed to PM ≤ 2.5 µm in aerodynamic diameter (PM2.5) and followed them from 26 September 2001 to 10 April 2002. We randomly assigned subjects in a double-blind fashion to receive either fish oil (n-3 PUFA) or soy oil. We measured PM2.5 levels indoors at the nursing home, and measured Cu/Zn SOD activity, LPO products, and GSH at different times during presupplementation and supplementation phases.
Results: Supplementation with either fish or soy oil was related to an increase of Cu/Zn SOD activity and an increase in GSH plasma levels, whereas exposure to indoor PM2.5 levels was related to a decrease in Cu/Zn SOD activity and GSH plasma levels.
Conclusion: Supplementation with n-3 PUFA appeared to modulate the adverse effects of PM2.5 on these biomarkers, particularly in the fish oil group. Supplementation with n-3 PUFA could modulate oxidative response to PM2.5 exposure.
Environmental exposure to particulate matter (PM) has been associated with increased cardiovascular mortality in the elderly (Aga et al. 2003; Devlin et al. 2003; Samet et al. 2000) and reductions in heart rate variability (HRV), a measure of cardiac autonomic regulation (Gold et al. 2000; Holguin et al. 2003; Park et al. 2005). Although not well understood, the mechanisms of PM-induced health effects are believed to involve inflammation and oxidative stress initiated by the formation of reactive oxygen species (ROS) within affected cells (Cho et al. 2005; Gonzalez-Flecha 2004). In vitro studies have shown that inhaled PM causes expression of nuclear factor kappa-B (NF-κB)-related genes and oxidant-dependent NF-κB activation (Jimenez et al. 2000; Shukla et al. 2000). To defend against the oxidative damage, cells use up their stores of a key antioxidant, glutathione; glutathione depletion can induce a state of cellular stress and the activation of additional intracellular signaling cascades that regulate the expression of cytokine and chemokine genes and widespread proinflammatory effects remote from the site of damage (Saxon and Diaz-Sanchez 2005). Data from PM samples of 20 European cities have shown that PM with an aerodynamic diameter ≤ 2.5 µm (PM2.5) has strong redox activity and is able to deplete artificial respiratory lining fluid of reduced glutathione (GSH) and ascorbate (Künzli et al. 2006). PM, depending on its toxicity, seems also to inhibit protective enzymes involved in oxidative stress responses [copper/zinc (Cu/Zn) superoxide dismutase (SOD), manganese SOD, glutathione peroxidase (GSH-Px), and glutathione reductase] (Hatzis et al. 2006). Alteration of autonomic function related to PM2.5 exposure appears to be partly associated with oxidative stress (Brook et al. 2003; Chahine et al. 2007).
Increased intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) has been shown to decrease the risk of cardiovascular events (GISSI Prevenzione Investigators 1999; Kris-Etherton et al. 2002; Leaf et al. 2003). The protective effect of n-3 PUFA seems to be linked in part to its cardiac antiarrhythmic properties (Christensen et al. 2001; Holguin et al. 2005; Kris-Etherton et al. 2002; Leaf 2001) and its anti-inflammatory effects (Calder 2006). Long-chain n-3 PUFA appears to act both directly (by replacing arachidonic acid as an eicosanoid substrate and inhibiting arachidonic acid metabolism) and indirectly by altering the expression of inflammatory genes through effects on transcription factor activation (Calder 2006). Fish oil has been shown to modulate endothelial activation possibly by reducing ROS and therefore leading to the subsequent inactivation of the NF-κB system of gene transcription. This role of oxygen scavenging would lead to the prevention of O2-generating hydrogen peroxide (H2O2) and thus prevent cell activation (De Caterina et al. 2000).
We have previously shown that exposure to PM2.5 is related to a decrease in HRV in elderly residents of a nursing home in Mexico City (Holguin et al. 2003) and that fish oil supplementation could increase HRV (Holguin et al. 2005) and modulate the adverse effects of PM2.5 on HRV (Romieu et al. 2005). We hypothesized that one of the mechanisms by which fish oil and, to a lesser extent, soy oil supplementation would modulate the adverse effects of PM2.5 on HRV would be by acting on the oxidative stress response, reducing the generation of ROS, modulating the use of GSH as part of the oxidative stress response, and increasing the activity of enzymes involved in response to oxidative stimuli. We tested this hypothesis in a randomized trial of fish oil versus soy oil supplementation to prevent reductions in cardiac autonomic function associated with PM exposure. During the trial, we measured Cu/Zn SOD activity, GSH, and LPO levels in plasma to evaluate the impact of fish oil and soy oil supplementation and exposure to PM2.5 on these biomarkers.
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