Suppression of Adjuvant Arthritis in Rats with Chronic Bromocriptine Treatment Does not Prevent Associated Oxidative Stress

We studied the effect of prolactin (PRL) inhibition by bromocriptine (BRC) in the first phase of adjuvant induced arthritis (AA), up to day 11 (BRC1-AA), and in the whole time course of AA, up to day 23 (BRC-AA), on the development of the disease in male Lewis rats. On day 24, arthritic rats showed inhibition of PRL secretion, but not PRL mRNA expression in adenopituitaries. BRC treatment suppressed PRL serum levels and PRL mRNA expression in adenopituitaries. In BRC1-AA group PRL levels and PRLmRNA were at the level of rats with AA. Serum corticosterone (CORT) was stimulated by AA from 16.9±5.8 to 59.1±8.7 ngml−1, p<0.05, to the same level in BRC-control (BRC-C) and BRC-AA group and further potentiated in BRC1-AA group (148.2<33.1 ngmr−1, p<0.05 vs. group with AA). Hind paw swelling was reduced but not completely inhibited in BRC1-AA group and totally prevented in BRC-AA rats as was the core temperature (36.5<0.1°C vs. 37.4<.0.1 °C in AA rats on day 23, p<0.01). Serum concentration of NO-2/NO−3 rose in rats with AA to 28.7±2.5 μmolL−1 against. 13.9±1.9 μmolL−1 in controls (p<0.01), remained elevated in BRC-AA group and was potentiated in BRC1-AA group (48.2±3.5 μmolL−1, p<0.01 vs. AA or BRC1-AA group) Thiobarbituric acid reactive substances (TBARS) and antioxidant capacity in the spleen were enhanced in rats with AA and to the same extent in BRC-AA or BRC1-AA groups. These results show a discrepancy between the suppression of clinical symptoms and persisting oxidative stress in AA rats after the BRC induced PRL inhibition. The potentiation of nintric oxide (NO) production after the sudden cessation of PRL inhibition during the disease may promote further joint damage.

[1]  T. Ishizuka,et al.  Immunological abnormality associated with the augmented nitric oxide synthesis in adjuvant-induced arthritis. , 1998, International journal of immunopharmacology.

[2]  E. Schmidt,et al.  Interleukin‐1‐Induced Plasticity of Hypothalamic CRH Neurons and Long‐Term Stress Hyperresponsiveness a , 1998, Annals of the New York Academy of Sciences.

[3]  F. Carrión,et al.  Bromocriptine induces immunological changes related to disease parameters in rheumatoid arthritis. , 1997, British journal of rheumatology.

[4]  Y. Ohta,et al.  TAK‐603 selectively suppresses Th1‐type cytokine production and inhibits the progression of adjuvant arthritis , 1997, Immunology.

[5]  D. Cardinali,et al.  Twenty-four-hour rhythms of serum ACTH, prolactin, growth hormone, and thyroid-stimulating hormone, and of median-eminence norepinephrine, dopamine, and serotonin, in rats injected with Freund's adjuvant. , 1997, Chronobiology international.

[6]  J. Kehayias,et al.  Adjuvant arthritis as a model of inflammatory cachexia. , 1997, Arthritis and rheumatism.

[7]  I. Laurindo,et al.  Nitric oxide synthase inhibitor influences prostaglandin and interleukin-1 production in experimental arthritic joints , 1997, Inflammation Research.

[8]  P. Strange,et al.  D2-like dopamine receptors are not detectable on human peripheral blood lymphocytes , 1996, Biological Psychiatry.

[9]  R. Wilder,et al.  Hormones and autoimmunity: animal models of arthritis. , 1996, Bailliere's clinical rheumatology.

[10]  B. Bauduceau,et al.  [Treatment of rheumatoid psoriasis with bromocriptine]. , 1995, Presse medicale.

[11]  P. Mapp,et al.  Hypoxia, oxidative stress and rheumatoid arthritis. , 1995, British medical bulletin.

[12]  G. Murrell,et al.  Nitric oxide activates metalloprotease enzymes in articular cartilage. , 1995, Biochemical and biophysical research communications.

[13]  C. Evans,et al.  N-monomethyl arginine, an inhibitor of nitric oxide synthase, suppresses the development of adjuvant arthritis in rats. , 1994, Arthritis and rheumatism.

[14]  S. Morikawa,et al.  Immunosuppressive activity of bromocriptine on human T lymphocyte function in vitro , 1994, Clinical and experimental immunology.

[15]  S. Morikawa,et al.  Immunosuppressive property of bromocriptine on human B lymphocyte function in vitro , 1993, Clinical and experimental immunology.

[16]  L. Caccavelli,et al.  Protein kinase C regulation of prolactin gene expression in lactotroph cells: involvement in dopamine inhibition. , 1993, Endocrinology.

[17]  M. Neidhart,et al.  Hyperprolactinaemia in hypophysectomized or intact male rats and the development of adjuvant arthritis. , 1992, Immunology.

[18]  C. Clevenger,et al.  Requirement for prolactin during cell cycle regulated gene expression in cloned T-lymphocytes. , 1992, Endocrinology.

[19]  N. Cortas,et al.  Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. , 1990, Clinical chemistry.

[20]  D. Larson,et al.  Freund's complete adjuvant induces ornithine decarboxylase activity in the central nervous system of male rats and triggers the release of pituitary hormones , 1990, Journal of Neuroimmunology.

[21]  J. Tresguerres,et al.  Role of the adrenal cortex in chronic stress-induced inhibition of prolactin secretion in male rats. , 1989, The Journal of endocrinology.

[22]  A. Whyte,et al.  Bromocriptine suppresses postpartum exacerbation of collagen-induced arthritis. , 1988, Arthritis and rheumatism.

[23]  S. Asa,et al.  The influence of pituitary hormones on adjuvant arthritis. , 1984, Arthritis and rheumatism.

[24]  S. Asa,et al.  Immunomodulation by bromocriptine. , 1983, Immunopharmacology.

[25]  Oliver H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[26]  M. Neidhart.  Bromocriptine has little direct effect on murine lymphocytes, the immunomodulatory effect being mediated by the suppression of prolactin secretion. , 1997, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[27]  L. Rauova,et al.  Effect of domperidone-induced hyperprolactinemia on selected immune parameters in healthy women. , 1995, Archivum immunologiae et therapiae experimentalis.