Background: Hormonal instability is linked to inflammation and oxidative stress (OS) through
common pathways. Thyroid hormones have been found to play a major part in the antioxidant balance
among many hormonal factors, since OS has been linked to both hypothyroidism and hyperthyroidism
in humans and animals. A number of research studies have demonstrated the antioxidant, antiinflammatory, and protective properties of melatonin receptor agonist Ramelteon (RML). Accordingly,
the aim of the current study was to examine the potential antioxidant and anti-inflammatory
properties of RML on OS induced by thyroid dysfunction (hyperthyroidism, hypothyroidism) in a rat
model
Methods: Thirty adult albino male rats (fed ordinary laboratory diet along the four weeks’ study), were
randomly divided into 5 groups; control group, experimentally-induced hypothyroid group (rats
received a single dose of 2 mg carbimazole/100g daily diluted in drinking water by oral gavage for four
weeks), hypothyroid group with administration of RML (10 mg/kg/day diluted in drinking water, via
oral gavage for four weeks), experimentally- induced hyperthyroid group (rats received a single daily
dose of 2μg/ml L-thyroxin diluted in drinking water by oral gavage for four weeks) and hyperthyroid
group with administration of RML (10 mg/kg/day diluted in drinking water, via oral gavage for four
weeks). All rats' body mass indices (BMIs) were assessed at the end of the experiment. Results: The
final BMI index, serum glucose, insulin, HOMA-IR, serum T3, serum T4, serum TSH, serum total
cholesterol, serum triglycerides, serum low density lipoprotein, serum tumor necrosis factor alpha
(TNF-α), serum interleukin-6 (IL-6), and serum oxidative stress markers, such as serum
malondialdehyde (MDA) and reduced glutathione (GSH), superoxide dismutase (SOD), were found to
differ statistically significantly between the hypothyroid and hyperthyroid groups. In terms of final BMI
index, serum glucose, insulin, HOMA-IR, total cholesterol, triglycerides, low density lipoprotein,
serum IL-6, TNF-α, and serum oxidative stress markers (MDA), (GSH), and (SOD), ramelteon
significantly reduced these levels. This suggests that ramelteon has anti-inflammatory and antioxidant
properties in thyroid dysfunction (hyperthyroidism, hypothyroidism). Conclusions: Ramelteon may be
able to diminish the oxidative and metabolic damage caused by hypo- and hyperthyroidism. Its
protective anti-obesity, hypoglycemic, hypolipidemic, antioxidant and anti-inflammatory properties
may contribute to its useful effects.