IN-VITRO ADDITION OF GLUTATHIONE TO BLOOD FROM ZINC-DEFICIENT RATS CORRECTS PLATELET DEFECTS - IMPAIRED AGGREGATION AND CALCIUM UP TAKE

Zinc deficiency in rats impairs platelet aggregation, and this defect is associated with the failure of platelets to take up external calciu m. Recent data show that the red cell plasma membrane from zinc-defici ent rats contains a lower than normal concentration of protein sulfhyd ryl groups, a defect that can be corrected readily in vivo by zinc rep letion. The purpose of this study was to determine the effect of zinc deficiency on sulfhydryl concentration of platelet membrane proteins a nd to determine if impaired platelet function can be corrected in vitr o by treatment of blood with glutathion (GS), a physiological reducing agent. Immature male rats were fed low zinc diets bused on egg white or EDTA-treated soy protein (<1 mg/kg Zn) and the same diets supplemen ted with 100 mg/kg Zn (control). For membrane analysis, rats were fed soy-based diets for 3 weeks; for reversal experiments they were fed eg g white-based diets for 2 weeks. Compared with controls, rats fed the low zinc diets had approximately 15% lower concentration of membrane p rotein sulfhydryls and their platelets exhibited impaired aggregation coupled with decreased calcium uptake when stimulated with ADP. Treatm ent of whole blood from deficient rats with 0.2 mM GSH restored aggreg ation and calcium uptake of washed platelets to control levels. The pr esence of red cells was essential for the reversal process in as much as treatment of platelet-rich-plasma or washed platelets with GSH had to effect. Treatment of control blood with GSH did not affect platelet aggregation, but decreased calcium uptake. The lower calcium uptake b y controls suggests that a feedback mechanism in deficient platelets w as not corrected by GSH treatment. The results show that selective sul fhydryl groups in platelet membranes are lost during zinc deficiency a nd that platelet function can be restored to normal by treatment of bl ood with GSH. There seems to be an association of oxidation-susceptibl e thiol groups with a calcium channel and that these groups are protec ted by normal physiological levels of zinc. (C) Elsevier Science Inc. 1997.