Hyperoxic exposure alters intracellular bioenergetics distribution in human pulmonary cells.

AIMS: Pulmonary oxygen toxicity is caused by exposure to a high fraction of inspired oxygen, which damages multiple cell types within the lung. The cellular basis for pulmonary oxygen toxicity includes mitochondrial dysfunction. The aim of this study was to identify the effects of hyperoxic exposure on mitochondrial bioenergetic and dynamic functions in pulmonary cells. MAIN METHODS: Mitochondrial respiration, inner membrane potential, dynamics (including motility), and distribution of mitochondrial bioenergetic capacity in two intracellular regions were quantified using cultured human lung microvascular endothelial cells, human pulmonary artery endothelial cells and A549 cells. Hyperoxic (95 % O2) exposures lasted 24, 48 and 72 h, durations relevant to mechanical ventilation in intensive care settings. KEY FINDINGS: Mitochondrial motility was altered following all hyperoxic exposures utilized in experiments. Inhomogeneities in inner membrane potential and respiration parameters were present in each cell type following hyperoxia. The partitioning of ATP-linked respiration was also hyperoxia-duration and cell type dependent. Hyperoxic exposure lasting 48 h or longer provoked the largest alterations in mitochondrial motility and the greatest decreases in ATP-linked respiration, with a suggestion of decreases in respiration complex protein levels. SIGNIFICANCE: Hyperoxic exposures of different durations produce intracellular inhomogeneities in mitochondrial dynamics and bioenergetics in pulmonary cells. Oxygen therapy is utilized commonly in clinical care and can induce undesirable decrements in bioenergy function needed to maintain pulmonary cell function and viability. There may be adjunctive or prophylactic measures that can be employed during hyperoxic exposures to prevent the mitochondrial dysfunction that signals the presence of oxygen toxcity.

Hyperbaric oxygen alters intracellular bioenergetics distribution in human dermal fibroblasts.

AIMS: Hyperbaric oxygen therapy (HBOT), used to promote wound healing, has limited efficacy in many clinical conditions. Wound healing exerts bioenergetic demands on cells that can exceed their intrinsic bioenergetic capacity to proliferate and migrate. The aim of this investigation was to quantify the effects of HBOT on mitochondrial dynamics and bioenergetics functions in cells relevant to wound healing. MAIN METHODS: High-resolution respirometry and fluorescence microscopy were used to quantify mitochondrial respiration, intermembrane potential, dynamics, including motility, and the intracellular distribution of mitochondrial bioenergetic capacity partitioned into perinuclear and cell peripheral regions in cultured human dermal fibroblasts. Cells were subjected to a range of gas mixtures and hyperbaric pressures, including conditions utilized in clinical care. KEY FINDINGS: Motility was reduced immediately following all HBOT exposures utilized in experiments. Inhomogeneities in intermembrane potential and respiration parameters were produced by different HBOT conditions. The partitioning of ATP-linked respiration was also HBOT-condition dependent. Application of HBOT at common clinical pressure and oxygen conditions resulted in the largest immediate decrement in mitochondrial motility and reductions in ATP-linked respiration in both the cell periphery and perinuclear zones. Aberrations in motility and respiration were also present 6 h after exposure. SIGNIFICANCE: HBOT produces intracellular distinctions and inhomogeneities in mitochondrial dynamics and bioenergetics. HBOT as is commonly applied in clinical medicine induced undesirable and persistent alterations in bioenergy function needed to support cell migration and/or proliferation. There may be alternative HBOT parameters that more effectively engender maintenance and adequacy of intracellular bioenergy supply to promote wound healing.

A double-blind randomized controlled trial of the effects of eicosapentaenoic acid supplementation on muscle inflammation and physical function in patients undergoing colorectal cancer resection.

BACKGROUND: Resection of colorectal cancer (CRC) initiates inflammation, mediated at least partly by NFĸB (nuclear factor kappa-light-chain-enhancer of activated B-cells), leading to muscle catabolism and reduced physical performance. Eicosapentaenoic acid (EPA) has been shown to modulate NFĸB, but evidence for its benefit around the time of surgery is limited. OBJECTIVE: To assess the effect of EPA supplementation on muscle inflammation and physical function around the time of major surgery. DESIGN: In a double-blind randomized control trial, 61 patients (age: 68.3 ± 0.95 y; 42 male) scheduled for CRC resection, received 3 g per day of EPA (n = 32) or placebo (n = 29) for 5-days before and 21-days after operation. Lean muscle mass (LMM) (via dual energy X-ray absorptiometry (DXA)), anaerobic threshold (AT) (via cardiopulmonary exercise testing (CPET)) and hand-grip strength (HG) were assessed before and 4-weeks after surgery, with muscle biopsies (m. vastus lateralis) obtained for the assessment of NF-ĸB protein expression. RESULTS: There were no differences in muscle NFĸB between EPA and placebo groups (mean difference (MD) -0.002; 95% confidence interval (CI) -0.19 to 0.19); p = 0.98). There was no difference in LMM (MD 704.77 g; 95% CI -1045.6 g-2455.13 g; p = 0.42) or AT (MD 1.11 mls/kg/min; 95% CI -0.52 mls/kg/min to 2.74 mls/kg/min; p = 0.18) between the groups. Similarly, there was no difference between the groups in HG at follow up (MD 0.1; 95% CI -1.88 to 2.08; p = 0.81). Results were similar when missing data was imputed. CONCLUSION: EPA supplementation confers no benefit in terms of inflammatory status, as judged by NFĸB, or preservation of LMM, aerobic capacity or physical function following major colorectal surgery. CLINICAL TRIALS REFERENCE: NCT01320319.

Eco-friendly synthesis and study of new plant growth promoters: 3,3'-Diindolylmethane and its derivatives.

3,3'-Diindolylmethane (DIM) derivatives 3a-k, prepared in one-pot from indoles 1a-k and hexamethylenetetramine (2) using ionic liquid [Bmim]BF(4) as eco-friendly recyclable solvent as well as catalyst, showed good plant growth promoting activity on Oryza sativa. Among the DIM derivatives synthesized 3c shows potent auxin like growth promoting activity.