Effects of Pantethine on Experimental Atherosclerosis in Rabbits

  • M. R. Malinow
  • B. Upson
  • M. Axthelm
  • P. McLaughlin
Conference paper
Part of the Proceedings in Life Sciences book series (LIFE SCIENCES)

Abstract

Panthetine is the disulfide dimer of panthetheine, the amide conjugate of pantothenic acid and cysteamine, which occurs naturally as a portion of coenzyme A and of acyl-carrier proteins (Wittwer et al. 1985). When pantethine was given to hyperlipopro-teinemic patients, it lowered plasma cholesterol levels (Maioli et al. 1984; Cattin et al. 1985) and elevated high density lipoprotein (HDL) cholesterol levels, especially the HDL2 fraction with a consequent increase in the HDL2/HDL3 ratio (Maioli et al. 1984). The effects on normolipidemic patients were less marked (Murai et al. 1983). In rabbits fed 0.5% cholesterol, pantethine also reduced total cholesterol levels and produced minor decreases in aortic atherosclerosis (Carrara et al. 1984); larger decreases were reported in a study involving a smaller number of animals and the effects were accentuated by combining the intake of pantethine with probucol (Tawara et al. 1986). We have investigated the effects of pantethine and of an ester derivative (tetra[3-(3-pyridinemethoxycarbonyl) propionyl]- pantethine tetratartrate, MG 28362) in rabbits receiving food additioned with cholesterol at the 0.2 or 0.25% level. Only results obtained with pantethine will be reported here.

Keywords

Cholesterol Formalin Toxicity Peroxida Cage 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Albers JJ, Warnick GR, Wiebe D, King P, Steiner P, Smith L, Breckenridge C, Chow A, Kuba K, Weidman S (1978) Multi-laboratory comparison of 3 heparin-MN2+ precipitation procedures for estimating cholesterol in high-density lipoprotein. Clin Chem 24:853–856PubMedGoogle Scholar
  2. Bon GB, Cazzolate G, Zago S, Avogaro P (1985) Effects of pantethine on in vitro peroxidation of low density lipoproteins. Atherosclerosis 57:99–106PubMedCrossRefGoogle Scholar
  3. Carrara P, Matturri L, Galbussera M, Lovati MR, Franceschini G, Sirtori CR (1984) Pantethine reduces plasma cholesterol and the severity of arterial lesions in experimental hypercholes-terolemic rabbits. Atherosclerosis 53:255–264PubMedCrossRefGoogle Scholar
  4. Cattin L, Da Col PG, Fonda M, Mameli MG, Pilotto L, Vanuzzo D, Feruglio GA (1985) Treatment of hypercholesterolemia with pantethine and fenofibrate; an open randomized study of 43 subjects. Curr Ther Res 38:386–394Google Scholar
  5. Farina R, Lovati MR, Raucci G, Sirtori CR (1980) Effects of pantethine on different models of experimental hyperlipidemia in rodents: a comparison with Clofibrate. Pharmacol Res Commun 14:499–510CrossRefGoogle Scholar
  6. Howard CF, Jr. (1979) Aortic atherosclerosis in normal and spontaneously diabetic Macaca nigra. Atherosclerosis 33:479–493PubMedCrossRefGoogle Scholar
  7. Maioli M, Pacifico A, Cherchi GM (1984) Effect of pantethine on the subfractions of HDL in dyslipidemic patients. Curr Ther Res 35:307–311Google Scholar
  8. Malinow MR, Pellegrino AA, Ramos EH (1958) Chemical and anatomical correlations in cholesterol-fed rabbits. Acta Physiol Lat Am 8:37–46PubMedGoogle Scholar
  9. Malinow MR, McLaughlin P, Papworth L, Kaito HK, Lewis L, McNulty WP (1976) A model for therapeutic intervention on established coronary atherosclerosis in a nonhuman primate. Adv Exp Med Biol 67:3–31PubMedGoogle Scholar
  10. Malinow MR, McLaughlin P, Stafford C, Kohler GO, Livingston AL (1980) Alfalfa saponins and alfalfa seeds: dietary effects in cholesterol-fed rabbits. Atherosclerosis 37:433–438PubMedCrossRefGoogle Scholar
  11. Murai A, Miyahara T, Tanaka T, Sako Y, Nishimura N, Kameyama M (1983) The effect of pantethine on lipid and lipoprotein abnormalities in survivors of cerebral infarction. Artery 12:234–243Google Scholar
  12. Rudel LL, Morris MD (1973) Determination of cholesterol using opthalaldehyde. J Lipid Res 14:364–366PubMedGoogle Scholar
  13. Shinomiya M, Matsuoka N, Shirai K, Morisaki N, Sasaki N, Murano S, Saito Y, Kumagai A (1980) Effect of pantethine on cholesterol ester metabolism in rat arterial wall. Atherosclerosis 36: 75–80PubMedCrossRefGoogle Scholar
  14. Snedecor GW, Cochran WG (1967) Statistical methods, 6th edn. State Univ Press, Ames, Iowa, pp 114–116Google Scholar
  15. Tawara K, Ishihara M, Ogawa H, Tomikawa M (1986) Effect of probucol, pantethine and their combinations on serum lipoprotein metabolism and on the incidence of atheromatous lesions in the rabbit. Jpn J Pharmacol 41:211–222PubMedCrossRefGoogle Scholar
  16. Wittwer CT, Gahl WA, Butler JDeB, Zatz M, Thoene JG (1985) Metabolism of pantethine in cystinosis. J Clin Invest 76:1665–1672PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • M. R. Malinow
  • B. Upson
  • M. Axthelm
  • P. McLaughlin
    • 1
    • 2
  1. 1.Oregon Regional Research Primate CenterBeavertonUSA
  2. 2.Oregon Health Sciences UniversityPortlandUSA

Personalised recommendations