Antioxidant effects on the prostaglandin endoperoxide synthetase product profile

Lipid peroxides are produced during the enzymatic conversion of arachidonic acid to prostaglandins, thromboxane, prostacyclin, and leukotrienes. These peroxides include hydroperoxides of arachidonic acid formed by lipoxygenase and the prostaglandin endoperoxide intermediates produced by action of prostaglandin endoperoxide synthetase. A number of steps in the arachidonate-dependent prostaglandin pathway are vulnerable to antioxidant affects. Such points in the biosynthetic sequence include prostaglandin endoperoxide synthetase, both the cyclooxygenase and peroxidase activity, prostacyclin synthetase, thromboxane synthetase, and lipooxygenase. Antioxidants added in vitro have been shown to affect prostaglandin synthesis. The present review will stress the limited information concerning the in vivo effect of antioxidants. Studies carried out in the investigator's laboratory on prostaglandin synthesis have utilized rats deficient or replete in vitamin E or propyl gallate (an antioxidant). Differentiation of germ cells in the testis of the male rat is arrested in vitamin E deficiency. Testis microsomal prostaglandin synthesis is altered prior to any overt morphological change. The effect of exogenous antioxidant in either rat testis or mammary gland preparation depends both on the type of antioxidant and the concentration. However, the effects of in vivo and in vitro antioxidant on arachidonate turnover are not identical. The physiological effect of antioxidants on prostaglandin synthesis appear to be specific.