Fish oil rich in eicosapentaenoic acid protects against oxidative stress-related renal dysfunction induced by TCDD in Wistar rats

Abstract

Humans are systemically exposed to persistent organic pollutants, of which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has become a major environmental concern. Exposure to TCDD results in a wide variety of adverse health effects which is mediated by oxidative stress through CYP1A1 activation and arachidonic acid metabolites. Eicosapentaenoic acid (EPA) exhibits antioxidant property and competes with arachidonic acid in membrane phospholipids and produces anti-inflammatory EPA derivatives. Since both EPA and its derivatives have been reported to enhance the antioxidant mechanism, the present study aimed at studying whether EPA could offer protection against TCDDinduced oxidative stress and nephrotoxicity in Wistar rats. Estimation of kidney markers (serum urea and creatinine) and histopathological studies revealed that EPA treatment significantly reduced TCDD-induced renal damage. TCDDinduced oxidative damage was reflected in a significant increase in CYP1A1 activity and lipid peroxide levels with a concomitant decline in non-enzymic antioxidant (GSH) and various enzymic antioxidants such catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), and glutathione peroxidase (GPx). In addition, TCDD-induced oxidative stress also resulted in decline in Na + -K + and Mg 2+ATPases activities with increase in Ca 2+ ATPases activity. Oral treatment with EPA showed a significant cytoprotection against TCDD-induced renal oxidative stress by decreased CYP1A1 activity and enhanced antioxidant status. TCDD-induced alterations in ATPase enzyme activities were also prevented by EPA treatment. Our results show clear evidence that EPA ameliorates TCDD-induced oxidative stress and kidney damage; thus suggest the potential of EPA as an effective therapeutic agent against toxic effects mediated through redox imbalance.

Dietary Omega-3 Polyunsaturated Fatty Acids Prevent Vascular Dysfunction and Attenuate Cytochrome P4501A1 Expression by 2,3,7,8-Tetrachlorodibenzo-P-Dioxin

“…Additionally, both EPA and DHA protect against TCDD-induced oxidative stress and hepatic and renal injury in rats in vivo (Palaniswamy et al, 2014;Turkez et al, 2011a). Notably, however, in our study TCDD did not increase oxidative stress markers or increase fatty acid autooxidation products in the liver.…”

“…Additionally, the n-3 PUFA diet significantly increases EPA and DHA, highly preferred endogenous fatty acid substrates for CYP1A1 (Arnold et al, 2010a,b), which could also reduce nonspecific CYP1A1 oxidation of other vascular fatty acid substrates. Others have reported that EPA reduces TCDD-induced CYP1A1 activity in vitro and in vivo (Palaniswamy et al, 2014(Palaniswamy et al, , 2015. The mechanism by which n-3 PUFAs reduce TCDDinduced CYP1A1 expression and activity is not known, although we did not observe a decrease in AHR expression in mice on the n-3 PUFAs diet.…”

The fatty acid profile of rainbow trout liver cells modulates their tolerance to methylmercury and cadmium

“…The dietary supplementation with ALA (1%) was reported to counteract the toxic effect of a MeHg contaminated diet (5 mg/kg body weight) by restoring the antioxidant defences and reducing lipid peroxidation in liver, kidneys, brain, plasma and red blood cells of rats Ghosh, 2012a andGhosh, 2012b). The authors suggested that the protective effect of ALA might be due to its bioconversion into EPA, which is known for its antioxidant properties (through enhancing the cellular antioxidant defences) (Palaniswamy et al, 2014;Shakouri Mahmoudabadi and Rahbar, 2014). However, our results show that the biological importance of ALA is not only due to its bioconversion into valuable HUFAs.…”

Eicosapentaenoic acid attenuates cigarette smoke-induced lung inflammation by inhibiting ROS-sensitive inflammatory signaling

“…In addition to its anti-inflammatory activity, administration of EPA has been reported to suppress ROS generation in vivo (Richard et al, 2008 ; van den Elsen et al, 2013 ). EPA also possesses antioxidant activity in type 2 diabetic patients (Mahmoudabadi and Rahbar, 2014 ), in rats exposed to organic pollutants (Palaniswamy et al, 2014 ) and against oxidative stress in adipocytes (Kusunoki et al, 2013 ). Thus, our findings are in good agreement with the above previously reported observations.…”

“…Additionally, EPA has been shown to suppress inflammatory responses to stimuli other than CS in a number of animal models (Okabe et al, 2011 ; Jia et al, 2012 ; Poudyal et al, 2013 ; Schuster et al, 2014 ) and in various cell types (Moon et al, 2007 ; Mickleborough et al, 2009 ; Mullen et al, 2010 ; Wang et al, 2010 ; Jinno et al, 2011 ; Jung et al, 2012 ; Magee et al, 2012 ; van den Elsen et al, 2013 ). Furthermore, EPA has been reported to possess antioxidant activity when prescribed to treat patients (Mahmoudabadi and Rahbar, 2014 ) or when used as in vitro (Richard et al, 2008 ; Kusunoki et al, 2013 ; van den Elsen et al, 2013 ) or in vivo preparations (Okabe et al, 2011 ; Palaniswamy et al, 2014 ). Thus, the antioxidant and anti-inflammatory properties of EPA make it a potential drug for the treatment of CS-induced lung inflammation.…”