Daily Variations in the Total Antioxidant Status, Nuclear Melatonin Receptor RORα, and Nuclear Factor NF‐ƙβ in the Lymphoid Organs of a Seasonally Breeding Tropical Squirrel, Funambulus pennanti

ABSTRACT

Melatonin‐mediated modulation of antioxidant enzyme activity is widely reported; however, the mechanism underlying this indirect free radical combating effect of melatonin remains unclear. In the present study, we explored the role of RORα and RORα dependent NF‐κB activation in mediating the effects of melatonin on the activity of antioxidant enzymes. The daily variation in the expression of RORα and NF‐κB along with the plasma melatonin level was assessed, and its possible association with the antioxidant enzyme activity in the lymphoid tissues of the Indian squirrel was evaluated during different reproductive seasons. Significant daily variation in the expression of RORα and NF‐κB was observed, which was inversely related to circulatory melatonin levels and the activity of antioxidant enzymes. The expression of RORα and NF‐κB was downregulated at the night when the plasma level of melatonin and activity of antioxidant enzymes namely superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were at their peak. Tissue melatonin can further act as a complementary factor in counteracting oxidative stress; hence, we also checked the lymphoid melatonin content over 24 h. No temporal variations were noted in the tissue melatonin content over the day. Likewise, no significant daily variation was noted in the total antioxidant status (TAS) of the lymphoid tissues. The absence of daily variation in the TAS can be attributed to the direct free radical scavenging activity of tissue melatonin in the spleen and thymus. The daily rhythms in the activity of antioxidant enzymes can be considered an integral part of the adaptive strategy that is regulated by the endogenous melatonin rhythm. However, the melatonin‐mediated regulation of the antioxidant enzyme activity is neither mediated by RORα nor NF‐κB dependent pathway.