In the gastrointestinal tract, prostaglandins are implicated as important mediators of normal physiological processes. Prostaglandin G/H synthase (PGHS) is the first enzyme leading to the formation of prostaglandins. Two forms exist: the constitutive PGHS-1 and the inducible PGHS-2 isoforms. The purpose of this study was to examine the expression of PGHS-1 and -2 in gastrointestinal tissues.
PGHS-1 and -2 expression and activity were examined in rat, dog, monkey, and human gastrointestinal tracts by immunoblot and biochemical assays.
PGHS-1 but not PGHS-2 protein was identified in all gastrointestinal tissues. PGHS-1 protein varied throughout the gastrointestinal tracts; interspecies differences were also noted. Immunohistochemical studies showed PGHS-1 staining of rat endothelial cells in all gastrointestinal regions; PGHS-2-specific staining was noted in a subset of macrophages in 3 of 22 rats examined. Elevated activity was shown in tissues expressing greater concentrations of PGHS-1 protein. Indomethacin, a nonsteroidal anti-inflammatory drug that inhibits both isoforms, inhibited prostaglandin synthesis, whereas NS-398, a selective PGHS-2 inhibitor, showed little or no inhibition of prostaglandin synthesis in gastrointestinal tissues.
These results indicate that prostaglandins produced in normal gastrointestinal tissue and required for normal physiological functioning are derived from the PGHS-1 isoform.
"COX enzyme can exist in two isoforms called COX-1 and COX-2 respectively. ASA is able to inhibit both, with a marked preference for COX-1 isoform which plays a fundamental role in maintaining gastrointestinal mucosa integrity (Blobaum and Marnett, 2007; Kargman et al., 1996). One approach to overcome the problem of ASA gastrotoxicity was the design of aspirin-nitric oxide (NO) donor hybrids (Bondarage and Janero, 2001; Koc and Kucukguzel, 2009). "
"COX has been recognized as the first enzyme in the formation of prostaglandin (PG) and thromboxane (TX) from arachidonic acid at the site of inflammation or after infection . COX-1 isozyme is expressed constitutively in many tissues, whereas COX-2 isozyme is expressed only at the site of inflammation . "
[Show abstract][Hide abstract] ABSTRACT: We demonstrated that hydrophobic derivatives of the nonsteroidal anti-inflammatory drug (NSAID)flufenamic acid (FA), can be formed into stable nanometer-sized prodrugs (nanoprodrugs) that inhibit the growth of glioma cells, suggesting their potential application as anticancer agent. We synthesized highly hydrophobic monomeric and dimeric prodrugs of FA via esterification and prepared nanoprodrugs using spontaneous emulsification mechanism. The nanoprodrugs were in the size range of 120 to 140 nm and physicochemically stable upon long-term storage as aqueous suspension, which is attributed to the strong hydrophobic interaction between prodrug molecules. Importantly, despite the highly hydrophobic nature and water insolubility, nanoprodrugs could be readily activated into the parent drug by porcine liver esterase, presenting a potential new strategy for novel NSAID prodrug design. The nanoprodrug inhibited the growth of U87-MG glioma cells with IC(50) of 20 μM, whereas FA showed IC(50) of 100 μM, suggesting that more efficient drug delivery was achieved with nanoprodrugs.
Available from: Hanumantha Rao Balaji raghavendran
"An earlier study demonstrates that fucoidan inhibits nitric oxide production in macrophages activated by LPS . Collagen deposition in the glandular regions of gastric mucosal tissue and its attenuation upon fucoidan treatment are evident with Masson's trichrome staining . Ulcerated myofibroblasts migrate towards the ulcer bases to induce granulation tissue, generating collagen fibrils and pro-inflammatory cytokines, such as TNF-α, and IL-6, to ultimately form ulcer scars . "
[Show abstract][Hide abstract] ABSTRACT: Gastric ulcers and related complications associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, represent a major global health problem. In the present study, we investigate the immunological activity of fucoidan against aspirin-induced gastric mucosal damage in rats. Thirty-six rats were randomly divided into the following, normal (Carboxy methyl cellulose 0.05 %), aspirin (Asp-400mg/kg) treated, fucoidan alone (Fu-0.02 g/kg, daily for 14 days) and Fu+Asp. Cytokines, total nitrite and nitrate (NOx) analysis and tissue localization of Cyclooxygenase 1, 2 and epidermal growth factor receptor (EGFR) were done using Elisa and immunohistochemistry respectively. Histopathology of gastric tissue, collagen deposition was performed using Hematoxylin and Eosin and Masson's trichrome were performed. Treatment of rats with a single dose of aspirin (400mg/kg, orally) led to significant alterations in the levels of total nitrite and nitrate (NOx), interleukins (IL-4, 6, 10, 12), tumor necrosis factor (TNF-α), and interferon gamma (IFN-γ). Notably, collagen deposition in glandular tissue and localization of cyclooxygenase 1, 2, and epidermal growth factor were considerably affected in aspirin-treated rats. These severities were prevented to a significant extent in rats pretreated with fucoidan (0.02 g/kg/day for two weeks orally). Our findings collectively indicate that the gastro-protective effect of fucoidan against aspirin-induced ulceration in rats is mediated through its immunomodulatory properties.
International immunopharmacology 11/2010; 11(2):157-63. DOI:10.1016/j.intimp.2010.11.002 · 2.47 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.