Journal of pineal research
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We tested the hypothesis that combined melatonin and autologous adipose-derived mesenchymal stem cells (ADMSC) was superior to either alone against small bowel ischemia-reperfusion (SBIR) injury induced by superior mesenteric artery clamping for 30 min followed by reperfusion for 72 hr. Male adult Sprague Dawley rats (n = 50) were equally categorized into sham-operated controls SC, SBIR, SBIR-ADMSC (1.0 × 10(6) intravenous and 1.0 × 10(6) intrajejunal injection), SBIR-melatonin (intraperitoneal 20 mg/kg at 30 min after SI ischemia and 50 mg/kg at 6 and 18 hr after SI reperfusion), and SBIR-ADMSC-melatonin groups. ⋯ Besides, antioxidant expressions at protein (NQO-1, GR, and GPx) and cellular (HO-1) levels progressively increased from SC to the combined treatment group (all P < 0.001). In conclusion, combined melatonin-ADMSC treatment offered additive beneficial effect against SBIR injury.
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Despite high in-hospital mortality associated with acute respiratory distress syndrome (ARDS), there is no effective therapeutic strategy. We tested the hypothesis that combined melatonin-mitochondria treatment ameliorates 100% oxygen-induced ARDS in rats. Adult male Sprague-Dawley rats (n = 40) were equally categorized into normal controls, ARDS, ARDS-melatonin, ARDS with intravenous liver-derived mitochondria (1500 μg per rat 6 hr after ARDS induction), and ARDS receiving combined melatonin-mitochondria. ⋯ Albumin level and inflammatory cells (MPO+, CD40+, CD11b/c+) from bronchoalveolar lavage fluid showed a pattern opposite to saO2 (all P < 0.001). Protein expression of indices of inflammation (MMP-9, TNF-α, NF-κB), oxidative stress (oxidized protein, NO-1, NOX-2, NOX-4), apoptosis (mitochondrial Bax, cleaved caspase-3, and PARP), fibrosis (Smad3, TGF-β), mitochondrial damage (cytochrome C), and DNA damage (γ-H2AX+) exhibited an opposite pattern compared to saO2 in all groups, whereas protein (HO-1, NQO-1, GR, GPx) and cellular (HO-1+) expressions of antioxidants exhibited a progressively increased pattern from normal controls to ARDS combined melatonin-mitochondria group (all P < 0.001). In conclusion, combined melatonin-mitochondrial was superior to either treatment alone in attenuating ARDS in this rat model.
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The purpose of this report is to emphasize the potential utility for the use of melatonin in the treatment of individuals who are infected with the Ebola virus. The pathological changes associated with an Ebola infection include, most notably, endothelial disruption, disseminated intravascular coagulation and multiple organ hemorrhage. Melatonin has been shown to target these alterations. ⋯ Moreover, melatonin has been successfully employed for the treatment of sepsis in many experimental and clinical studies. Based on these factors, as the number of treatments currently available is limited and the useable products are not abundant, the use of melatonin for the treatment of Ebola virus infection is encouraged. Additionally, melatonin has a high safety profile, is readily available and can be orally self-administered; thus, the use of melatonin is compatible with the large scale of this serious outbreak.
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Melatonin is a strong anti-oxidant that has beneficial effects against early brain injury (EBI) following a subarachnoid hemorrhage (SAH) in rats; protection includes the reduction of both mortality and neurological deficits. The molecular mechanisms underlying these clinical effects in the SAH model have not been clearly identified. This study examined the influence of melatonin on brain edema secondary to disruption of the blood-brain barrier (BBB) and the relationship between these effects and pro-inflammatory cytokines in EBI following SAH using the filament perforation model of SAH in male Sprague-Dawley rats. ⋯ Melatonin treatment also repressed cortical levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), which were increased in EBI 24 hr after SAH. To further identify the mechanism of this protection, we demonstrated that administration of melatonin attenuated matrix metallopeptidase 9 expression/activity and vascular endothelial growth factor expression, which are related to the inflammatory response and BBB disruption in EBI after SAH. Taken together, this report shows that melatonin prevents disruption of tight junction proteins which might play a role in attenuating brain edema secondary to BBB dysfunctions by repressing the inflammatory response in EBI after SAH, possibly associated with regulation of pro-inflammatory cytokines.
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This study tested whether combined therapy with melatonin and apoptotic adipose-derived mesenchymal stem cells (A-ADMSCs) offered additional benefit in ameliorating sepsis-induced acute kidney injury. Adult male Sprague-Dawley rats (n = 65) were randomized equally into five groups: Sham controls (SC), sepsis induced by cecal-ligation and puncture (CLP), CLP-melatonin, CLP-A-ADMSC, and CLP-melatonin-A-ADMSC. Circulating TNF-α level at post-CLP 6 hr was highest in CLP and lowest in SC groups, higher in CLP-melatonin than in CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups (all P < 0.001). ⋯ Changes in protein expressions of inflammatory (RANTES, TNF-1α, NF-κB, MMP-9, MIP-1, IL-1β), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF-β) markers, reactive-oxygen-species (NOX-1, NOX-2), and oxidative stress displayed a pattern identical to that of kidney injury score among the five groups (all P < 0.001). Expressions of antioxidants (GR+, GPx+, HO-1, NQO-1+) were lowest in SC group and highest in CLP-melatonin-A-ADMSC group, lower in CLP than in CLP-melatonin and CLP-A-ADMSC groups, and lower in CLP-melatonin- than in CLP-A-ADMSC-tretaed animals (all P < 0.001). In conclusion, combined treatment with melatonin and A-ADMSC was superior to A-ADMSC alone in protecting the kidneys from sepsis-induced injury.