Cell injury and death caused by: Oxidative stress and Ischemia reperfusion

Production of ROS

• Mitochondria during ATP production

• Neutrophils and macrophages

Removal of ROS

• Spontaneous decay

• Enzymes (e.g. superoxide dismutase (SOD))

• Antioxidants (e.g. vitamin C or E)

What can increase ROS and cause oxidative stress (too much ROS)?

1. Infection

   1. Activation of inflammatory cells to destroy microbes

2. Ionizing radiation and some chemicals

3. Ischemia reperfusion injury

Myocytes (muscle cells) in the heart of a 65-year-old male experiences ischemia from an occluded coronary artery.

If no reperfusion

Tissue downstream will die

Myocytes (muscle cells) in the heart of a 65-year-old male experiences ischemia from an occluded coronary artery.

If reperfusion occurs

Tissue may recover (Not without a price)

1. Generate ROS →

2. Decrease antioxidants →

3. Reperfusion injury →

How does increased ROS cause cell injury?

1. Lipid peroxidation

   1. Damage membranes

   2. Reversible then necrosis

2. Single stranded DNA breaks

3. Cross-link or fragment proteins

   1. Increase protein degradation (structural proteins and enzymes)

   2. Protein misfolding

   3. Irriversable