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Strain Differences in Antioxidants in Rat Models of Cardiovascular Disease Exposed to Ozone
Citation:
Hatch, G., K. Chrissman, Judy Schmid, J. Richards, W. Ward, M. Schladweiler, A. Ledbetter, AND U. Kodavanti. Strain Differences in Antioxidants in Rat Models of Cardiovascular Disease Exposed to Ozone. INHALATION TOXICOLOGY. Informa Healthcare USA, New York, NY, 27(1):54-62, (2015).
Impact/Purpose:
We report here that large differences exist in basal and O3 – induced concentrations of low molecular weight antioxidants in rat strains considered to be normal, as well as in the CVD strains. Some antioxidants concentrations were associated with others across all rat strains. Antioxidant enzyme activities were not altered by the O3 exposure we used. Expression of antioxidant genes yielded some insights.
Description:
We examined the hypothesis that antioxidant substances and enzymes in lung, heart and in bronchoalveolar lavage fluid (BALF) are altered in response to 03 in cardiovascular disease and/or metabolic syndrome (CVD)-prone rat models. CVD strains [spontaneously hypertensive (SH), SH stroke-prone (SHSP), SHHF/Mcc heart failure obese (SHHF), insulin-resistant JCR:LA-cp obese (JCR) and Fawn-Hooded hypertensive (FHH)] were compared with normal strains [Wistar, Sprague-Dawley (SD) and Wistar Kyoto (WKY)]. Total glutathione (GSH + GSSG or GSx), reduced ascorbate (AH2), uric acid (UA) and antioxidant enzymes were determined in lung, heart and BALF immediately (0 h) or 20-h post 4-h nose-only exposure to 0.0, 0.25, 0.5 and 1.0 ppm 03. Basal- and 03-induced antioxidant substances in tissues varied widely among strains. Wistar rats had a robust 03-induced increase in GSx and AH2 in the lung. Two CVD strains (JCR and SHHF) had high basal levels of AH2 and GSx in BALF as well as high basal lung UA. Across all strains, high BALF GSx was only observed when high BALF AH2 was present. CVD rats tended to respond less to 03 than normal. High-basal BALF AH2 levels were associated with decreased 03 toxCity. In summary , large differences were observed between both normal and CVD rat strains in low-molecular weight antioxidant concentrations in lung, BALF and heart tissue. Wistar (normal) and JCR and SHHF (CVD) rats appeared to stand out as peculiar in terms of basal- or 03-induced changes. Results elucidate interactions among antioxidants and air pollutants that could enhance understanding of cardiopulmonary disease.
