Effects of cyclooxygenase inhibitor pretreatment on nitric oxide production, nNOS and iNOS expression in rat cerebellum

Abstract

1 The therapeutic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is thought to be due mainly to its inhibition of cyclooxygenase (COX) enzymes, but there is a growing body of research that now demonstrates a variety of NSAIDs effects on cellular signal transduction pathways other than those involving prostaglandins. 2 Nitric oxide (NO) as a free radical and an agent that gives rise to highly toxic oxidants (peroxynitrile, nitric dioxide, nitron ion), becomes a cause of neuronal damage and death in some brain lesions such as Parkinson and Alzheimer disease, and Huntington's chorea. 3 In the present study, the in vivo effect of three NSAIDs (lysine clonixinate (LC), indomethacine (INDO) and meloxicam (MELO)) on NO production and nitric oxide synthase expression in rat cerebellar slices was analysed. Rats were treated with (a) saline, (b) lipopolysaccharide (LPS) (5 mg kg À1 , i.p.), (c) saline in combination with different doses of NSAIDs and (d) LPS in combination with different doses of NSAIDs and then killed 6 h after treatment. 4 NO synthesis, evaluated by Bred and Snyder technique, was increased by LPS. This augmentation was inhibited by coadministration of the three NSAIDs assayed. None of the NSAIDs tested was able to modify control NO synthesis. 5 Expression of iNOS and neural NOS (nNOS) was detected by Western blotting in control and LPS-treated rats. LC and INDO, but not MELO, were able to inhibit the expression of these enzymes. 6 Therefore, reduction of iNOS and nNOS levels in cerebellum may explain, in part, the antiinflammatory effect of these NSAIDs and may also have importance in the prevention of NOmediated neuronal injury.

Pneumococcal Cell Wall-Induced Meningitis Impairs Adult Hippocampal Neurogenesis

“…Minocycline acts as an inhibitor of microglial activation and has previously been shown to reduce iNOS expression, e.g., in global brain ischemia (58) or in a model of Huntington's disease (9). Indomethacin also reduced iNOS upregulation in cerebellar homogenates of LPS-treated rats (11). However, additional mediators may be involved in the modulation of neurogenesis in the context of inflammation.…”

Ibuprofen intake increases exercise time to exhaustion: A possible role for preventing exercise‐induced fatigue

“…Consequently, the production of cytokines secreted by macrophages at the injury site is hampered, reducing the inflammatory response (Rainsford, ). Furthermore, researchers have shown that ibuprofen reduces the activity of inducible isoform of nitric oxide synthase, which produces changes in transmembrane ion flux (Liles & Flecknell, ) and is also involved in inflammatory processes (Di Girolamo et al., ). Interestingly, a study described by Da Silva et al.…”

Inhibitory effects of novel tetrahydropyridine derivatives on nitric oxide and reactive oxygen species production in glioma cells

“…NSAIDs such as indomethacin and ibuprofen also reduce cytokineactivated iNOS mRNA in a murine macrophage cell line [Ogawa et al, 2000]. NSAIDs such as indomethacin and lysine clonixinate also attenuate LPS-induced iNOS expression in vivo [DiGirolamo et al, 2003]. However, the attenuating effects of NSAIDs on NO may also contribute to the adverse side effects on the gastric mucosal tissue, with long-term administration.…”