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Mitochondrial-targeted antioxidants protect against mechanical ventilation-induced diaphragm dysfunction and skeletal muscle atrophy

A technology of skeletal muscle and diaphragm, applied in the field of aromatic cationic peptide composition, which can solve the problems of incomplete defense

Inactive Publication Date: 2012-12-19
UNIV OF FLORIDA RES FOUNDATION INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, inhibition of xanthine oxidase activity does not fully protect against the effects of skeletal muscle disuse-induced oxidative stress or MV-induced oxidative stress (concomitant atrophy and weakness)

Method used

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  • Mitochondrial-targeted antioxidants protect against mechanical ventilation-induced diaphragm dysfunction and skeletal muscle atrophy
  • Mitochondrial-targeted antioxidants protect against mechanical ventilation-induced diaphragm dysfunction and skeletal muscle atrophy
  • Mitochondrial-targeted antioxidants protect against mechanical ventilation-induced diaphragm dysfunction and skeletal muscle atrophy

Examples

Experimental program
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Embodiment 1

[0244] A. Test design

[0245] The purpose of this experiment was to demonstrate the role of mitochondrial ROS emission in MV-induced diaphragmatic weakness and to demonstrate the effect of a mitochondrial-targeted antioxidant peptide (SS-31) on mitochondrial function and rat diaphragm. Two different groups of rats (1 and 2) were treated as follows.

[0246] 1. Conscious and spontaneously breathing rats

[0247] To determine the effect of a mitochondrial-targeted antioxidant (SS-31) on diaphragmatic contractile function, fiber cross-sectional area (CSA), and mitochondrial function in conscious, spontaneously breathing rats, animals were treated as follows. Animals (n = 6 / group) were randomly assigned to one of two test groups: (1) control group - injected (intraperitoneal, i.p.) saline every 3 hours for 12 hours; and (2) Mitochondrial antioxidant group - Injection (intraperitoneal, i.p.) of SS-31 every 3 hours for 12 hours. Diaphragmatic contractile function, fibrous CSA, ...

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Abstract

The present disclosure provides methods and compositions for preventing or treating MV-induced or disuse-induced skeletal muscle infirmities in a mammalian subject. The methods further include administering to the subject an effective amount of an aromatic-cationic peptide.

Description

[0001] governmental support [0002] This invention was made with Government support under Grant R01HL08783 awarded by the National Institutes of Health. The US Government has certain rights in this invention. [0003] Cross References to Related Applications [0004] This application claims priority to US Provisional Application No. 61 / 308508, filed February 26, 2010, which is incorporated herein by reference in its entirety. technical field [0005] Disclosed herein are methods and compositions comprising aromatic-cationic peptides for preventing and treating skeletal muscle weakness (eg, weakness, dysfunction, and / or muscle wasting). In particular, disclosed herein are methods and compositions for the prevention and treatment of mechanical ventilation (MV)-induced diaphragmatic weakness and disuse-induced skeletal muscle weakness. Background technique [0006] The following descriptions are provided for the reader's convenience. None of the information provided or ref...

Claims

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Application Information

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IPC IPC(8): A61K38/05
CPCA61K38/06A61P39/06A61P21/00
Inventor 黑兹尔·H·司徒斯科特·克莱恩·鲍尔斯
Owner UNIV OF FLORIDA RES FOUNDATION INC
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