title: Gonadotropin-releasing hormone agonist prevents l-arginine induced immune dysfunction independent of gonadal steroids: Relates with a decline in elevated thymus and brain nitric oxide levels.
abstract: The present study was carried out to find out the effect of leuprolide, a gonadotropin-releasing hormone (GnRH) receptor agonist, on l-arginine induced immunosuppression, and relates with brain and thymus levels of nitric oxide (NO). Further, the effect of leuprolide was studied in sham operated, ovariectomized and castrated mice to understand the role of sex steroids in l-arginine induced immunosuppression. Treatment with l-arginine (250, 500, 1000 mg/kg/i.p. for 7 days) increased brain and thymus levels of NO; measured by using 'NO Measuring Instrument' (Innovative Instruments Inc., USA) in dose dependent manner. It also decreased cellularity, relative weight of thymus, DNA fragmentation, humoral, and cell mediated immunity response to sheep RBC. Prior treatment of leuprolide (100μg/mouse, s.c. for 7 days) prevented l-arginine induced rise in brain and thymus tissue levels of NO as well as the changes in immunological parameters. The protective effect of leuprolide against l-arginine induced immunosuppression and rise in brain and tissue nitric oxide levels was even evident in ovariectomized and castrated mice, suggesting that the observed effect of leuprolide is independent of sex steroids, and correlated with its ability to prevent l-arginine induced rise in CNS and peripheral immune tissue levels of NO.
authors.affiliation: University Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj, Nagpur University, Mahatma Jyotiba Fuley Shaikshanik Parisar, Amravati Road, Nagpur, 440 033, MS, India.
authors.forename: Meenal P
authors.initials: MP
authors.lastname: Ullewar
authors.affiliation: Kamla Nehru College of Pharmacy, Borkhedi Gate, Near Railway Crossing, Butibori, Nagpur, 441108, MS, India. Electronic address: umathesn@hotmail.com.
authors.forename: Sudhir N
authors.initials: SN
authors.lastname: Umathe
mesh_terms: D000818:Animals; D001120:Arginine / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007165:Immunosuppression Therapy; D016729:Leuprolide / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D012739:Gonadal Steroid Hormones; D009573:Nitrites; D009569:Nitric Oxide; D007987:Gonadotropin-Releasing Hormone; D001120:Arginine; D016729:Leuprolide
keywords: Apoptosis; Cell-mediated immunity; Gonadotropin-releasing hormone; Humoral immunity; Nitric oxide