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

Russel J. Reiter, Dun Xian Tan, Seok Joong Kim, Lucien C. Manchester, Wenbo Qi, Joaquin J. Garcia, Javier C. Cabrera, Gamal El-Sokkary, Veronica Rouvier-Garay

Research output: Contribution to journalArticle

161 Scopus citations

Abstract

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 influence the accumulation of oxidatively damaged products as the animals aged. Rats 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 controls. Aging in the pineal-intact animals was associated with increased levels 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 of protein carbonyls (in the liver). Likewise, advanced age was associated with a significant decrease in membrane fluidity (increased membrane rigidity) of hepatic microsomes in pineal-intact rats. For all of these parameters and in a number of organs, pinealectomy caused further increases in the indices of oxidative damage. Consistent with previous suggestions, the implications of these findings is that aging is associated with the augmented accumulation of oxidatively damaged macromolecules and that these increases are exaggerated when a relative melatonin deficiency is induced by pinealectomy. The findings are consistent with the idea that the accelerated accumulation of oxidatively damaged products after pinealectomy was due to reduction in melatonin since it functions as a free radical scavenger and antioxidant. 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.

Original languageEnglish (US)
Pages (from-to)157-173
Number of pages17
JournalMechanisms of Ageing and Development
Volume110
Issue number3
DOIs
StatePublished - Oct 22 1999

Keywords

  • 8-Hydroxydeoxyguanosine
  • Aging
  • Lipid peroxidation
  • Melatonin
  • Membrane fluidity
  • Pinealectomy
  • Protein carbonyls

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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