Related Experiment Video
Updated: Jun 1, 2026
Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue
Published on: March 23, 2015
Melatonin and structurally similar compounds have differing effects on inflammation and mitochondrial function in
D A Lowes1, A M Almawash, N R Webster
1Academic Unit of Anaesthesia and Intensive Care, School of Medicine and Dentistry, University of Aberdeen, UK.
Background:
Development of organ dysfunction associated with sepsis is due in part to oxidative damage to mitochondria. Melatonin regulates the sleep-wake cycle and also has potent antioxidant activity. The aim of this study was to determine the effects of melatonin and other structurally related compounds on mitochondrial function, endogenous glutathione (GSH), and control of cytokine expression under conditions mimicking sepsis.
Methods:
Human endothelial cells were treated with lipopolysaccharide (LPS) plus peptidoglycan G (PepG) to simulate sepsis, in the presence of melatonin, 6-hydroxymelatonin, tryptamine, or indole-3-carboxylic acid. Nuclear factor κB (NFκB) activation, interleukin (IL)-6 and IL-8, total glutathione, mitochondrial membrane potential, and metabolic activity were measured.
Results:
LPS and PepG treatment resulted in elevated IL-6 and IL-8 levels preceded by activation of NFκB (all P<0.0001). Treatment with all four compounds resulted in lower IL-6 and IL-8 levels, and lower NFκB activation (P<0.0001). Loss of mitochondrial membrane potential and endogenous glutathione was seen when cells were exposed to LPS/PepG, but these were maintained in cells co-treated with melatonin, tryptamine, or 6-hydroxymelatonin (P<0.05), but not indole-3-carboxylic acid. Metabolic activity decreased after exposure to LPS/PepG and was maintained by melatonin and 6-hydroxymelatonin at the highest concentrations only.
Conclusions:
We have shown that in addition to melatonin, other structurally related indoleamine compounds have effects on NFκB activation and cytokine expression, GSH, mitochondrial membrane potential, and metabolic activity in endothelial cells cultured under conditions mimicking sepsis. Further work is needed to determine whether these compounds represent therapeutic approaches for disrupting the oxidative stress-inflammatory response signalling pathway in sepsis.
Related Concept Videos
01:17Sedatives and Hypnotics Drugs: Miscellaneous Agents
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
01:19Management of Insomnia
01:25Acute Inflammation III: Local and Systemic Effects
01:38Inflammation