A Kaur1, S Jindal, I P Kaur, K Chopra. 1. Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India.
Abstract
OBJECTIVE: Estrogen deprivation after menopause is associated with increased oxidative stress. The present study was designed to study the role of sesamol (3,4-methylenedioxyphenol), a phenolic antioxidant and anti-inflammatory molecule, in oxidative stress-induced changes in three major affected organ systems, the central nervous system, the cardiovascular system and the skeletal system in ovariectomized rats, a widely used animal model of menopause. DESIGN: Animals were divided into eight different groups (n = 6-8). Five groups underwent ovariectomy; starting from the 2nd day of ovariectomy, three of these groups received sesamol (2, 4, 8 mg/kg) and the fourth group was administered α-tocopherol (100 mg/kg) orally for 7 weeks. The fifth ovariectomized group did not receive any drug treatment. Rats in the naïve (non-operated) and sham-operated groups did not receive any drug treatment, while the eighth group consisted of naïve animals which were treated for 7 weeks with only sesamol 8 mg/kg orally daily. After 7 weeks, animals were subjected to testing of behavioral paradigms (elevated plus maze and Morris water maze for assessment of anxiety and memory, respectively) 24 h after the last dose. After behavioral studies, animals were sacrificed for various biochemical estimations. RESULT: Administration of sesamol (2, 4, 8 mg/kg orally) to ovariectomized rats for 7 weeks significantly and dose-dependently improved memory, attenuated anxiety, decreased oxidative stress in brain, improved the serum lipid profile and reduced serum tumor necrosis factor-α levels when compared with ovariectomized control rats. Similar protective effects were observed in the case of the skeletal system studies. Sesamol increased the bone ash content and the mechanical stress parameters in treated groups. CONCLUSION: The results emphasize the involvement of oxidative stress and inflammation in the development of ovariectomy-induced pathophysiological changes and point towards the therapeutic potential of sesamol in menopausal pathologies.
OBJECTIVE: Estrogen deprivation after menopause is associated with increased oxidative stress. The present study was designed to study the role of sesamol (3,4-methylenedioxyphenol), a phenolic antioxidant and anti-inflammatory molecule, in oxidative stress-induced changes in three major affected organ systems, the central nervous system, the cardiovascular system and the skeletal system in ovariectomized rats, a widely used animal model of menopause. DESIGN: Animals were divided into eight different groups (n = 6-8). Five groups underwent ovariectomy; starting from the 2nd day of ovariectomy, three of these groups received sesamol (2, 4, 8 mg/kg) and the fourth group was administered α-tocopherol (100 mg/kg) orally for 7 weeks. The fifth ovariectomized group did not receive any drug treatment. Rats in the naïve (non-operated) and sham-operated groups did not receive any drug treatment, while the eighth group consisted of naïve animals which were treated for 7 weeks with only sesamol 8 mg/kg orally daily. After 7 weeks, animals were subjected to testing of behavioral paradigms (elevated plus maze and Morris water maze for assessment of anxiety and memory, respectively) 24 h after the last dose. After behavioral studies, animals were sacrificed for various biochemical estimations. RESULT: Administration of sesamol (2, 4, 8 mg/kg orally) to ovariectomized rats for 7 weeks significantly and dose-dependently improved memory, attenuated anxiety, decreased oxidative stress in brain, improved the serum lipid profile and reduced serum tumor necrosis factor-α levels when compared with ovariectomized control rats. Similar protective effects were observed in the case of the skeletal system studies. Sesamol increased the bone ash content and the mechanical stress parameters in treated groups. CONCLUSION: The results emphasize the involvement of oxidative stress and inflammation in the development of ovariectomy-induced pathophysiological changes and point towards the therapeutic potential of sesamol in menopausal pathologies.