Augmentation of indices of oxidative damage in life-long melatonin-deficient rats

The chief pineal secretory product, melatonin, is an efficient free radical scavenger and antioxidant. The current study tested whether the life-long reduction of endogenous melatonin levels due to pinealectomy would influenc e the accumulation of oxidatively damaged products as the animals aged. Rat s were either pinealectomized or sham operated when they were 2-months-old. At 25 months of age these animals were killed along with 2-month-old contr ols. Aging in the pineal-intact animals was associated with increased level s of lipid peroxidation products (malondialdehyde and 4-hydroxyalkenals in the lung, kidney and skin), rises in an oxidatively damaged DNA. product (8 -hydroxy-deoxyguanosine in liver, kidney and pancreas), and in the levels o f protein carbonyls (in the liver). Likewise, advanced age was associated w ith a significant decrease in membrane fluidity (increased membrane rigidit y) of hepatic microsomes in pineal-intact rats. For all of these parameters and in a number of organs, pinealectomy caused further increases in the in dices of oxidative damage. Consistent with previous suggestions, the implic ations of these findings is that aging is associated with the augmented acc umulation of oxidatively damaged macromolecules and that these increases ar e exaggerated when a relative melatonin deficiency is induced by pinealecto my. The findings are consistent with the idea that the accelerated accumula tion of oxidatively damaged products after pinealectomy was due to reductio n in melatonin since it functions as a free radical scavenger and antioxida nt. On the other hand, other pineal secretory products that were reduced as a consequence of pineal removal may have also been responsible for some of the observed changes. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.