Topical Captopril as a Novel Agent Against Hypertrophic Scar Formation in New Zealand White Rabbit Skin

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Author(s): 
Gholamreza Safaee Ardekani, MD; Saeed Ebrahimi, MD; Mitra Amini, MD, MPH; Fatemeh Sari Aslani, MD; Farhad Handjani, MD; Gholamhossein Ranjbar Omrani, MD; Leila Safaee Ardekani, BS; Seyed Hamidreza Hosseini Alhashemi, MD; Behrooz Kasraee, MD1

Disclosure: The authors would like to thank the Vice Chancellor for research at the Jahrom School of Medical Sciences, Jahrom, Iran for supporting this research. Contract no. P/M/526–26.2.85.

Collagen constitutes the majority of extracellular matrix in tissues such as bone, cartilage, and especially the skin, and plays a major role in the process of wound healing. Following cutaneous injury, fibroblasts migrate to the site of trauma and produce collagen fibers that will increase the tensile strength of the scar. Abnormal wound healing due to overproduction of collagen could result in hypertrophic scar (HS) or keloid formation,1 which are the two main cosmetically disfiguring complications for which few treatment options are currently available. Several medical and surgical modalities alone or in various combinations have been utilized for the prevention or treatment of these disorders, but most of these treatment options have proved inadequately effective.2–4 The majority of such therapeutic approaches have been associated with various adverse effects and high recurrence rates.5

Recently, the importance of angiotensin II (ANG II) in stimulating collagen synthesis and fibroblast proliferation in the cardiac fibroblasts has been noted,6–8 and the role of inhibition of ANG II for the reduction of collagen formation in cardiac muscles proven.6–8

Recent studies have demonstrated that in addition to the cardiac muscle, ANG II, and angiotensin converting enzyme are produced locally in the skin and that these components increase during the process of wound healing.9,10 ANG II augments collagen synthesis, induces fibroblast proliferation,11,12 and suppresses matrix metalloproteinase activity—the key enzyme for interstitial collagen degradation.6,13,14

This study was undertaken to determine whether the topical application of captopril, an inhibitor of ANG II production, has any preventive potential against HS formation in New Zealand white rabbit skin.

Materials and Methods

Chemicals, animals, and topical formulations. Captopril was commercially obtained from Sigma Chemicals (Buchs, Switzerland). Propylene glycol, paraffin, and formaldehyde were purchased from Merck (Darmstadt, Germany). Ethanol (96%) was obtained from Zachariah Chemicals (Jahrom, Iran).

Six 3-month-old female New Zealand white rabbits (weight ranging from 1.5 to 2.5 kg) were provided by Pasteur Research Institute (Tehran, Iran). The animals were individually kept in aluminum cages with a controlled temperature (23 ± 2˚C) and relative humidity of 30%–50% and a 12-h light/dark cycle. The rabbits were fed standard commercial rodent chow obtained from the Animal Research Farm, Shiraz University of Medical Sciences, (Shiraz, Iran). Rabbits were acclimated for 2 weeks before experimentation and had free access to food and water before and during the trial.

Captopril was dissolved in a vehicle consisting of 70% ethanol and 30% propylene glycol at 5% concentration at the Biochemistry Laboratory of Jahrom School of Medical Sciences, (Jahrom, Iran). The vehicle alone served as the negative control.

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