Melatonin and a 21-Aminosteroid Attenuate Shock after Hemorrhage but Differentially Affect Serum Cytokines

Sullivan, Dennis J.; Shelby, Jane; Shao, Yuanlin; Affleck, David G.; Hinson, Douglas; Barton, Richard G.

doi:10.1006/jsre.1996.0299

Cited by 21 publications

(9 citation statements)

References 7 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Melatonin also decreased plasma nitrite/nitrate concentrations at 18 and 24 h after LPS administration (43). Attenuation by melatonin of the hypotensive effect and lethality after hemorrhage or interleukin-2 therapy have also been reported (44)(45)(46). Furthermore, melatonin exerts potent antiinflammatory effects and reduces NO production in murine models of carrageenan-induced inflammation (47).…”

Section: Discussionmentioning

confidence: 89%

“…Therefore, it is unlikely that endogenously produced melatonin may be present in sufficient concentrations to suppress the process of iNOS induction. However, the current data may offer a novel mechanism for melatonin's anti-shock and anti-inflammatory effects (24,(43)(44)(45)(46)(47). Melatonin's regulatory effect on gene expression appears to be selective in the sense that melatonin can inhibit the expression of some genes and at the same time enhance the expression of others.…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Melatonin inhibits expression of the inducible isoform of nitric oxide synthase in murine macrophages: role of inhibition of NFκB activation

et al. 1998

View full text Add to dashboard Cite

The role of melatonin as an immunomodulator is well established. Recent reports showed that melatonin exerts protective effects in septic and hemorrhagic shock and in inflammation. The expression of the inducible isoform of nitric oxide synthase (iNOS) makes an important contribution to the pathophysiology of shock and inflammation. We studied, in cultured murine macrophages, the role of melatonin in the regulation of the expression of iNOS and defined the mode of melatonin's action. Our results show that melatonin, at 1 microM-1 mM, decreased the production of nitrite/nitrate (the breakdown products of NO) as well as the production of 6-keto-prostaglandin F1alpha (the major stable breakdown product of prostacyclin) in macrophages stimulated with bacterial lipopolysaccharide (10 microg/ml). We observed that melatonin reduces iNOS steady-state mRNA levels and iNOS protein expression in the same concentration range (1 microM-1 mM). Melatonin, up to 10 mM, exerted only a slight direct inhibitory effect on iNOS activity. Using iNOS promoter-luciferase constructs, we found that melatonin inhibits iNOS promoter activation. Inhibition of iNOS expression was associated with inhibition of activation of the transcription factor nuclear factor kappa B (NFkappaB). We conclude that melatonin inhibits NO production in immunostimulated macrophages mainly by inhibiting the expression of iNOS. This is due to inhibition of iNOS transcription, in part through inhibition of NFkappaB activation. Inhibition of iNOS-derived NO production by melatonin may contribute to the anti-inflammatory effects of this pineal secretory product.

show abstract

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 95%

Melatonin inhibits expression of the inducible isoform of nitric oxide synthase in murine macrophages: role of inhibition of NFκB activation

et al. 1998

View full text Add to dashboard Cite

show abstract

“…Variable doses and treatment periods, ranging from 30 µg/100 g to 500 mg/kg and from single dose to long-term intravenous infusion, have been used in previous studies in the literature (4,(11)(12)(13). Treatment protocol in the present study was designated as two different doses, twice a day, the aim being to prolong the effective plasma concentration of melatonin.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Exogenous Melatonin on Experimental Colonic Anastomosis

Özdoğan

Oruk

Renda

et al. 2005

Acta Chirurgica Belgica

View full text Add to dashboard Cite

show abstract

“…immunostimulated macrophages [30], and decreases serum TNF-a production in trinitrobenzene sulphonic acid-induced colitis and cardiopulmonary bypass operations in rats [17,31]. Melatonin also reduced serum IL-6 levels after HS in mice [32]. Melatonin has the capability of scavenging both oxygen-and nitrogenbased reactants, including those formed from peroxynitrite, and blocking NF-kB, which further decreases pro-inflammatory cytokines (TNF-a, and IL-6) [9].…”

Section: Discussionmentioning

confidence: 94%