Oxidative/nitrosative stress, autophagy and apoptosis as therapeutic targets of melatonin in idiopathic pulmonary fibrosis

ABSTRACT

Introduction: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease associated with disruption of alveolar epithelial cell layer and expansion of fibroblasts/myofibroblasts. Excessive levels of oxidative/nitrosative stress, induction of apoptosis, and insufficient autophagy may be involved in IPF pathogenesis; hence, the targeting of these pathways may ameliorate IPF.

Areas covered: We describe the ameliorative effect of melatonin on IPF. We summarize the research on IPF pathogenesis with a focus on oxidative/nitrosative stress, autophagy and apoptosis pathways and discuss the potential effects of melatonin on these pathways.

Expert opinion: Oxidative/nitrosative stress, apoptosis and autophagy could be interesting targets for therapeutic intervention in IPF. Melatonin, as a potent antioxidant, induces the expression of antioxidant enzymes, scavenges free radicals and modulates apoptosis and autophagy pathways. The effect of melatonin in the induction of autophagy could be an important mechanism against fibrotic process in IPF lungs. Further clinical studies are necessary to determine if melatonin could be a candidate for treating IPF.

KEYWORDS:

• Pulmonary fibrosis
• melatonin
• oxidative stress
• autophagy
• apoptosis

Article highlights

• Idiopathic pulmonary fibrosis (IPF) is associated with apoptosis of alveolar epithelial cells and expansion of fibroblasts/myofibroblasts in lung tissue.

• Excessive level of oxidative/nitrosative stress and insufficient autophagy are proposed to be a mechanism for epithelial cell apoptosis.

• Melatonin is a potent antioxidant stimulating the expression of GSH and antioxidant enzymes and scavenging free radicals.

• Melatonin has protective effects on oxidant/antioxidant status of the lungs in various pathologic conditions.

• The regulatory effect of melatonin on apoptosis and autophagy processes has been reported in various in vivo and in vitro experiments.

• The antioxidant properties of melatonin and its modulatory effect on apoptosis and autophagy pathways suggest that melatonin could be a promising agent for IPF treatment.

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Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded. This work was supported by Iran University of Medical Sciences.