Melatonin administration differentially affects age-induced alterations in daily rhythms of lipid peroxidation and antioxidant enzymes in male rat liver

Sep 11, 2012Biogerontology

Melatonin affects daily changes in liver oxidative stress and antioxidants differently with age in male rats

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Abstract

Aging in male Wistar rats is associated with increased oxidative stress, indicated by significant changes in lipid peroxidation and antioxidant enzyme activities.

Oxidative stress indicators in the liver show daily rhythms that vary with age.
In 12 and 24 months old rats, lipid peroxidation is significantly elevated compared to 3 months old rats.
The GSH/GSSG ratio decreases and antioxidant enzyme activities decline in older rats.
In 3 months old rats, lipid peroxidation peaks at ZT-12, while antioxidant activities are lowest at this time.
Melatonin administration appears to restore some rhythmic patterns of antioxidants and lipid peroxidation in aging rats.

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A central clock/pacemaker, suprachiasmatic nuclei of the hypothalamus coordinates and entrains circadian oscillations in the peripheral tissues such as the liver, kidney, heart, lungs etc. called peripheral clocks. These also have endogenous circadian oscillations. The circadian rhythms of antioxidants present in cytosol signify redox state of the cell during day/night cycle. The liver has a major impact on homeostasis through its control on serum protein composition and plays a pivotal role in the metabolism of nutrients, drugs, hormones, and metabolic waste products and undergoes substantial changes in structure and function upon aging. In present study, the temporal patterns of oxidative stress indicators in liver were studied. Daily rhythms of lipid peroxidation end products, reduced glutathione (GSH), oxidized glutathione (GSSG) and antioxidant enzymes such as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were studied in liver at variable time points (Zeitgeber Time (ZT) 0, 6, 12 and 18) in three age groups: 3 (adult), 12 and 24 months old male Wistar rats. There was increase in oxidative stress in 12 and 24 months old rats indicated through a significant increase in lipid peroxidation, decrease in GSH/GSSG ratio and antioxidant enzyme activities. In 3 months old rats, lipid peroxidation was maximum at ZT-12 whereas GSH, SOD and CAT activities were minimum at ZT-12. The maximum level in 24 h i.e., acrophases of lipid peroxidation, GPx, SOD and CAT activities in liver cell free extracts altered upon aging. As melatonin, messenger of darkness, an endogenous synchronizer of rhythm, an antioxidant and an antiaging drug, declines with aging we studied the effects of melatonin on activities of these antioxidant enzymes in aging rats. Melatonin administration resulted in differential restoration of acrophases, amplitude, mean as well as daily rhythms of lipid peroxidation and antioxidants in liver of 12 and 24 months old rats.

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Melatonin administration differentially affects age-induced alterations in daily rhythms of lipid peroxidation and antioxidant enzymes in male rat liver

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