Journal of pineal research
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Endoplasmic reticulum stress-mediated cell apoptosis is implicated in the development of cancer. Melatonin induces apoptosis in hepatocellular carcinoma (HCC) in experimental studies, but the effects of melatonin on endoplasmic reticulum (ER) stress-induced apoptosis in HCC have not been tested. Differences in ER stress-induced apoptosis in human hepatoma cells and normal human hepatocyte were investigated by exposure to tunicamycin (ER stress inducer). ⋯ Furthermore, down-regulation of COX-2 expression using the COX-2 inhibitor, celecoxib, increased tunicamycin-induced apoptosis concomitant with the up-regulation of pro-apoptotic transcription factor CHOP (GADD153) and down-regulation of B-cell lymphoma 2/Bcl-2-associated X protein (Bcl-2/Bax) ratio, suggesting that inhibition of COX-2 sensitized human hepatoma cells to ER stress-induced apoptosis. Interestingly, co-treatment with tunicamycin and melatonin also decreased the expression of COX-2 and significantly increased the rate of apoptosis by elevating the levels of CHOP and reducing the Bcl-2/Bax ratio. These results demonstrate that melatonin sensitizes human hepatoma cells to ER stress-induced apoptosis by down-regulating COX-2 expression, increasing the levels of CHOP and decreasing the Bcl-2/Bax ratio.
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Randomized Controlled Trial
Pain in neonatal intensive care: role of melatonin as an analgesic antioxidant.
Endotracheal intubation is a common painful procedure in newborn care. Neonates are more sensitive to pain than older infants, children, and adults, and this hypersensitivity is further exacerbated in preterm neonates. The aim of this study was to evaluate the analgesic activity of melatonin during endotracheal intubation of the newborn by using the Neonatal Infant Pain Scale (NIPS) and Premature Infant Pain Profile (PIPP) score. ⋯ The differences were statistically significant at 12, 24, 48, and 72 hr (P < 0.001). Pro-inflammatory and anti-inflammatory cytokines (IL-6, IL-8, IL-10 and IL-12) were higher in the common sedation and analgesia group than in melatonin-treated infants at 24, 48, 72 hr and 7 days (P < 0.001). This study suggests the use of melatonin as an adjunct analgesic therapy during procedural pain, especially when an inflammatory component is involved.