Abstract
Sulfur dioxide (SO2) is a ubiquitous air pollutant, present in low concentrations in the urban air, and in higher concentrations in the working environment. While toxicological reports on SO2 have extensively dealt with the pulmonary system, essentially no data are available on the effects of chronic exposure to this pollutant on intermediary metabolism, although some biochemical changes in lipid metabolism have been detected. The present investigation was aimed at evaluating the effects of sub-chronic exposure to SO2 on concentrations of serum lipids/lipoproteins and on glucose metabolism, in animal models of hypercholesterolemia and diabetes. A specially designed controlinert atmosphere chamber was used, where male Sprague-Dawley rats fed on either standard or cholesterol enriched (HC) diets, as well as streptozotocin diabetics, were exposed to SO2 at 5 and 10 ppm, 24 h per day for 14 days. In rats, both on a standard diet and on a HC regimen, SO2 exposure determined a significant dose-dependent increase in plasma triglycerides, up to +363% in the 10 ppm HC exposed animals. This same gas concentration significantly reduced HDL cholesterol levels. In contrast, exposure of diabetic animals to 10 ppm SO2 resulted in a fall (−41%) of plasma and liver triglycerides and in a concomitant increase (+62%) of plasma HDL cholesterol. This discrepancy could apparently be related to diverging effects of SO2 exposure on plasma insulin levels in the different animal groups. Kinetic analyses of triglyceride synthesis carried out in rats on a standard diet revealed, in exposed animals, a significant reduction in the secretory rate, in spite of the concomitant hypertriglyceridemia. These findings suggest that SO2 exposure can markedly modify major lipid and glycemic indices, also indicating a differential response in normo/hyperlipidemic versus diabetic animals.
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References
Amdur MO (1969) Toxicological appraisal of particulate matter, oxides of sulfur, and sulfuric acid. J Air Pollut Control Assoc 19: 638–644
Ayres SH, Evans RG, Buehler ME (1979) The prevalence of carboxyhemoglobinemia in New Yorkers and its effects on the coronary and systemic circulation. Prey Med 8: 323
Bar-On H, Roheim, PS, Eder HA (1976) Serum lipoproteins and apolipoproteins in rats with streptozotocin-induced diabetes. J Clin Invest 57: 714–721
Baskurt OK (1988) Acute hematologic and hemorheologic effects of sulfur dioxide inhalation. Arch Environ Health 43: 344–348
Beck-Speier I, Lenz AG, Godleski JJ (1994). Responses of human neutrophils to sulfite. J Toxicol Environ Health 41: 285–297
Bliss CI (1967) Comparison of several groups In: Bliss CI (ed) Statistics in Biology. Mc Graw-Hill, New York, N.Y., pp 232–237
Bruckdorfer KR (1990) Free radicals, lipid peroxidation and atherosclerosis. Curr Opin Lipid 1: 529–535
Bucolo G, David H (1973) Quantitative determination of serum triglyceride. Clin Chem 19: 476–478
Carlson LA, Ballantyne D (1976) Changing relative proportion of apolipoprotein C-II and C-III of very low density lipoproteins in hypertriglyceridemia. Atherosclerosis 23: 563–568
Chute EP, Barbosa JJ, Rupp WM, Rohde RD, Goldenberg FJ, Hitchcock CR, Buchwald H (1985) Reduction of plasma cholesterol and LDL-cholesterol by continuous intravenous insulin infusion. Surgery 98: 656–661
Committee on Sulfur Oxides (1978) Epidemiological studies of health effects of sulfur oxides. In: Sulfur oxides. National Academy of Science, Washington DC, pp 180–209
Dethloff LA, Gladen BC, Gilmore LB, Hook GER (1987) Quantitation of cellular and extracellular constituents of the pulmonary lining by using bronchoalveolar lavage. Am Rev Respir Dis 136: 899–907
Devalia JL, Rusznak C, Herdman MJ, Trigg CJ, Tarraf H, Davies RJ (1994) Effect of nitrogen dioxide and sulfur dioxide on airway response of mild asthmatic patients to allergen inhalation. Lancet 344: 1668–1671
Donovan DH, Williams SJ, Charles JM, Menzel DB (1977) Ozone toxicity: effect of dietary vitamin E and polyunsaturated fatty acids. Toxicol Lett 1: 135–139
Esterbauer H, Dieber-Rotheneder M, Waeg G, Striegl G, Ashy A, Sattler W, Jurgens G (1990) Biochemical, structural and functional properties of oxidized low-density lipoproteins. Chem Res Toxicol 3: 77–92
Folch J, Less M, Sloan-Stanley GA (1957) A simple method for isolation and purification of total lipids from animal tissues. J Biol Chem 226: 497–502
Garfinkel AS, Nilsson-Ehle P, Schotz MC (1976) Regulation of lipoprotein lipase induction by insulin. Biochem Biophys Acta 124: 264–273
Gunnison AF (1981) Sulphite toxicity: a critical review of in vitro and in vivo data. Food Cosmet Toxicol 19: 667–682
Gunnison AF, Sellakumar A, Currie D, Snyder EA (1987) Distribution, metabolism and toxicity of inhaled sulfur dioxide and endogenously generated sulfite in the respiratory tract of normal and sulfite oxidase-deficient rats. J Toxicol Environ Health 21: 141–162
Hackney JD (1976) Relationship between air pollution and cardiovascular disease; a review. In: Finkel AJ, Duel WC (eds) Clinical implications of air pollution research. Publishing Sciences Group, Acton, pp 89–106
Haider SS (1985) Effects of exhaust pollutant sulfur dioxide on lipid metabolism of guinea pig organs. Ind Health 23: 81–87
Kannel WB, Castelli VP, Gordon T, McNamara PM (1971) Serum cholesterol, lipoproteins and the risk of coronary heart disease: the Framingham Study. Ann Int Med 74: 1–12
Kinnunen PKJ, Jackson RL, Smith LC, Gotto AM Jr, Sparrow JT (1977) Activation of lipoprotein lipase by native and synthetic fragments of human plasma apolipoprotein C-II. Proc Natl Acad Sci USA 74: 4848–4853
Like AA, Rossini AA (1976) Streptozotocin-induced pancreatic insulitis: new model of diabetes mellitus. Science 193: 415–417
Loven D, Schedl H, Wilson H, Daabees TT, Steigink LD, Diekus M, Oberley L (1986) Effect of insulin and oral glutathione on glutathione levels and superoxide dismutase activity in organs of rats with streptozotocin-induced diabetes. Diabetes 35: 503–507
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275
Magni F, Cancellieri M, Del Puppo M, Galli-Kienle M (1992) Diabetes-induced alteration of HMGCoA reductase forms in rat livers. Acta Diabetol 28: 211–214
Maliwal BI, Guthrie FE (1982) In vitro uptake and transfer of chlorinated hydrocarbons among human lipoproteins. J Lipid Res 23: 474–479
Medeiros MHG, Bechara EJH, Naoum PC (1983) Oxygen toxicity and hemoglobinemia in subjects from a highly polluted town. Arch Environ Health 38: 11–16
Nath N, Wiener R, Harper AE, Elvehjiem CA (1959) Diet and cholesterolemia, part 1 (development of a diet for the study of nutritional factors affecting cholesterolemia in rats). J Nutr 67: 289–296
Nilsson-Ehlep, Garfinkel AS, Schotz MC (1980) Lipolytic enzymes and plasma lipoprotein metabolism. Annu Rev Biochem 49: 667–693
Reaven GM, Greenfield MS (1981) Diabetic hypertriglyceridemia. Evidence for three clinical syndromes. Diabetes 30: 66–75.
Riedel F, Krämer M, Scheibenbogen C, Rieger CHL (1988) Effects of SO2 exposure on allergic sensitization in the guinea pig. J Aller Clin Immunol 82: 527–534
Rosenman KD, (1979) Cardiovascular disease and environmental exposure. Br J Ind Med 36: 85–97
Sagai M, Ichinose T, Oda H, Kubota K (1981) Studies on the biochemical effects of nitrogen dioxide. Lipids 16: 64–67
Scanu AM, Edelstein C (1971) Solubility in acqueous solutions of ethanol of the small molecular weight peptides of the serum very low density and high density lipoproteins: relevance to the recovery problem during delipidation of serum lipoproteins. Anal Biochem 44: 576–588
Schimmel H (1978) Evidence for possible acute health effects of ambient air pollution from time series analysis. Methodological questions and some new results based on New York city daily mortality: 1963–1976. Bull NY Acad Med [Second Series] 54: 1052–1108
Schurr PE, Schultz JR, Parkinson TM (1971) Triton induced hyperlipidemia in rats as an animal model for screening hypolipidemic drugs. Lipids 7: 68–74
Sheppard D (1988) Sulfur dioxide and asthma — a double-edged sword? J Aller Clin Immunol 82: 961–964
Simonelli C, Eaton P (1978) Effect of clofibrate on in vivo triglyceride production and clearance in genetically hyperlipidemic rats. Atherosclerosis 29: 269–275
Smith CJ, Steichen TJ (1993) The atherogenic potential of carbon monoxide. Atherosclerosis 99: 137–147
Snyder LM, Fortier NL, Trainor J, Jacobs J, Leb L, Lubin S, Chiu D, Shohet S, Mohandas N (1985) Effect of hydrogen peroxide exposure on normal human erythrocyte deformability, morphology, surface characteristics and spectrin-hemoglobin cross-linking. J Clin Invest 76: 1971–1977
Til HP, Feron VJ, de Groot A, Van der Wal P (1972) The toxicity of sulphite. II. Short- and long-term feeding studies in pigs. Food Cosmet Toxicol 10: 463–467
Topping DL (1977) Metabolic effects of carbon monoxide in relation to atherogenesis. Atherosclerosis 26: 129–137
Tunnicliffe WS, Burge PS, Ayres JG (1994) Effect of domestic concentrations of nitrogen dioxide on airway responses to inhaled allergen in asthmatic patients. Lancet 344: 1733–1736
Wang CS, McConathy WJ, Kloer HU, Alaupovic P (1985) Modulation of lipoprotein lipase activity by apolipoproteins. Effect of apolipoprotein C-III. J Clin Invest 75: 384–390
Weber K, Osborn M (1969) The reliability of molecular weight determinations by sodium dodecyl sulphate-poly acrylamide gel electrophoresis. J Biol Chem 244: 4406–4411
Wilson MA, Miles LEM (1977) Radioimmunoassay of insulin. In: Abraham GE (ed) Handbood of radioimmunoassay. M Dekker, New York, pp 275–293
Wolinsky H (1985) Atherosclerosis. In: Wyngaarden JB, Smith LH (eds) Textbook of medicine. Sandeers Company, Philadelphia, pp 281–284
Xu X, Gao J, Dockery DW, Chen Y (1994) Air pollution and daily mortality in residential areas of Beijing, China. Arch Environ Health 49: 216–222
Yoshino J, Iwai M, Kazumi T, Matsushita M, Morita M, Matsuba K, Iwatani I, Baba S (1989) Effect of dietary fructose on triglyceride turnover in streptozotocin-diabetic rats. Atherosclerosis 79: 41–46
Yoshino G, Matsushita M, Maeda E, Naka Y, Nagata K, Morita M, Matsuba K, Kazumi T, Kasuga M (1992) Effect of long-term insulin deficiency and insulin treatment on the composition of triglyceride-rich lipoproteins and triglyceride turnover in rats. Atherosclerosis 92: 243–250
Zlatkis A, Zak B, Boyle AJ (1953) A new method for direct determination of serum cholesterol. J Lab Clin Med 41: 486–496
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Lovati, M.R., Manzoni, C., Daldossi, M. et al. Effects of sub-chronic exposure to SO2 on lipid and carbohydrate metabolism in rats. Arch Toxicol 70, 164–173 (1996). https://doi.org/10.1007/s002040050256
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DOI: https://doi.org/10.1007/s002040050256