title: Pharmacological and biochemical studies on the protective effects of melatonin during stress-induced behavioral and immunological changes in relation to oxidative stress in rats.
abstract: Stress is known to precipitate neuropsychiatric diseases, and depending upon its nature and intensity it can also influence the functioning of the immune system. Melatonin (N-acetyl-5-methoxy tryptamine) a pineal gland hormone and potent antioxidant is known to protect against many diseases. Effect of melatonin in stress-induced neuro-immunomodulation is not well elucidated. Therefore in the present study, the protective effects of melatonin were evaluated in restraint stress (RS)-induced behavioral and immunological changes in rats. RS for 1 h significantly reduces (i) percentage of open-arm entries and (ii) percentage of time spent on open-arm in elevated plus maze (EPM) test parameters (p < 0.01) and significant increase in MDA levels in brain homogenate when compared to non-RS control groups (p < 0.05). In immunological studies, both humoral and cell-mediated immune responses to antigen were significantly suppressed by RS for 1 h for 5 consecutive days, as evidenced by significant reduction in (i) anti-SRBC antibody titre, (ii) PFC counts, (iii) percentage change in paw volume, and (iv) Th1 (IFN-γ) and Th2 (IL-4) cytokine levels (p < 0.001 in all parameters). These RS-induced immunological changes were associated with significantly increased lipid peroxidation (MDA) levels in serum and significantly decreased activity of (i) SOD, (ii) CAT, and (iii) GSH levels in RS (X5)-exposed group (p < 0.02). Pretreatment with melatonin (10, 50, and 100 mg/kg) significantly reversed these RS-induced changes in EPM test parameters and humoral and cell-mediated immunological parameters, as well as oxidative stress markers in a dose-dependent manner by differential degrees (p < 0.001). Results are strongly suggestive of the involvement of free radicals during stress-induced neurobehavioral and immunological changes. These changes were significantly restored by melatonin pretreatment. We can conclude that melatonin may have a protective role during such stress-induced neuro-immunomodulation.
authors.affiliation: a Department of Pharmacology & Therapeutics, King George's Medical University, UP, Lucknow-226003, India.|b Department of Pharmacology, V. P. Chest Institute, University of Delhi, Delhi-11007, India.
authors.forename: Rishi
authors.initials: R
authors.lastname: Pal
authors.affiliation: b Department of Pharmacology, V. P. Chest Institute, University of Delhi, Delhi-11007, India.
authors.forename: Kavita
authors.initials: K
authors.lastname: Gulati
authors.affiliation: c Department of Biochemistry, University College of Medical Sciences (UCMS) & GTB Hospital, Delhi-110095, India.
authors.forename: B D
authors.initials: BD
authors.lastname: Banerjee
authors.affiliation: b Department of Pharmacology, V. P. Chest Institute, University of Delhi, Delhi-11007, India.
authors.forename: Arunabha
authors.initials: A
authors.lastname: Ray
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D005609:Free Radicals / Q000009:adverse effects; D005978:Glutathione / Q000378:metabolism; D056747:Immunomodulation / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical / Q000379:methods; D013312:Stress, Physiological / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D020011:Protective Agents; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005978:Glutathione; D008550:Melatonin
keywords: behavior; comportement; cytokine; free radicals; immunity; immunité; melatonin; mélatonine; oxidants; oxydants; radicaux libres; restraint stress; stress de contention