FREE RADICALS IN HEALTH AND DISEASE

Free radicals, i.e. atoms or molecules with one or more unpaired electrons in their outermost orbits, are regularly formed in body during normal metabolic activity and eliminated by various antioxidant mechanisms.

Three most important free radicals in human context are: singlet oxygen (O^-), superoxide and peroxide anions and hydroxyl radicals.

Sources: Free radical excess is implicated to:

• Exogenous or environmental sources, e.g. smoke, air pollutants, radiation, ultraviolet rays, etc. or

• Endogenous or metabolic sources, e.g. infections, cellular ischemia/hypoxia, toxic tissue injury.

Antioxidants: Important antioxidant substances in body may be broadly divided into three categories:

a. Metabolic enzymes, e.g. superoxidase mutase, catalase, glutathione peroxidase, etc.

b. Metal ion chelators, e.g. plasma proteins, transferrin, ceruloplasmin, etc.

c. Oxygen scavengers, e.g. vitamins (A, E, C) and minerals (selenium, zinc).

Pathology: Free radical tissue injury is considered as an important cause of altered cellular permeability and metabolism, leading to early cell death in innumerable disease processes, including:

• Hyperoximia-related problems in preterms, e.g. retino­pathy of prematurity or bronchopulmonary dysplasia,

• Hypoxic-ischemic injuries, e.g. neonatal enterocolitis, hypoxic-ischemic encephalopathy,

• Sepsis/septic shock,

• Metabolic disorders, e.g. kwashiorkor, Wilson disease, hemochromatosis, etc.,

• Hemolytic anemia or malignancies, and

• Premature atherosclerosis or aging in adults, etc.

Prevention of free radical injury depends on avoidance of environmental risk factors, early treatment of primary disease and adequate consumption of natural antioxidants, i.e.

Treatment: Recently, many synthetic antioxidants have been used in selected cases of suspected free radical injury, e.g. xanthine oxidase inhibitors, e.g. allopurinol, N-acetylcysteine, recombinant enzymes, e.g. glutathione peroxidase analogues, superoxide dismutase, coenzyme Q derivatives, etc. or natural antioxidants (as above), with equivocal results.

BIBLIOGRAPHY

1. Kinjawadekar U et al. Severe acute malnutrition: Standard treatment guidelines. Indian Academy of Pediatrics. 2022.

2. Ministry of Health and Family Welfare. Operational Guidelines on Facility Based Management of Children with Severe Acute Malnutrition. New Delhi: Ministry of Health and Family Welfare; 2017.

3. Kumar P, Gupta P. Severe Acute Malnutrition. New Delhi: CBS Publishers amp; Distributors; 2017.

4. World Health Organization. Updates on the management of severe acute malnutrition in infants and children. Geneva: World Health Organization; 2013.

5. Indian Academy of Pediatrics. Consensus Statement on Integrated Management of Severe Acute Malnutrition. Indian Pediatrics. 2013;50:399.

6. Gupta P. Indian Academy of Pediatrics Revised (2021). Guidelines on Prevention and Treatment of Vitamin D Deficiency and Rickets Indian Pediatr. 2022;59:142.