A scientific review of the chemistry of wound healing and hypochlorous acid, why purity of the molecule in a wound cleansing solution matters and why hypochlorite is no longer a must use ingredient.
Objective: Chlorinated species such as molecular chlorine, hypochlorous acid, and sodium hypochlorite all have antimicrobial properties, yet these differ in the cellular response they elicit, which is important in the context of wound healing.
The purpose of this study is to review the laws of physical chemistry, and published literature to reach conclusion on the most desired species from the three mentioned here.
Methods: We did a survey of published literature on two key subjects, which is the toxicity of hypochlorite anion, which is present in Dakin’s solution as the predominant species, and hypochlorous acid solutions.
In particular, we were interested in solutions that have very low concentrations of the hypochlorite anion (commonly present in Dakin’s solution or bleach) and solutions that have hypochlorous acid above 250 ppm which is present in some wound solutions where the concentration of hypochlorous is the highest amongst commercially available products.
Result: The cytotoxicity of the hypochlorite species is well published. This cytotoxicity was observed in Dakin’s solution that was diluted to 0.00005%, which corresponds to 5 ppm. Hypochlorous acid, too, can be cytotoxic, at very high concentrations, however, at 250 -350 ppm seems to be completely benign. The antimicrobial preservative efficacy at that 250-350 ppm hypochlorous acid is high, with most tested bacterial and fungal species tested perishing in a matter of 15-30 seconds.
Conclusion: Eukaryotic cells have protective mechanisms to be able to handle hypochlorous acid at a concentration such as 250-300 ppm. Prokaryotes such as unicellular microbes have not evolved to be protected against hypochlorous acid. However, eukaryotic cells do not seem have protective mechanisms against the hypochlorite, even at low concentrations, and thus are affected by the presence of hypochlorite anion.
Trademarked Items (if applicable):
References (if applicable): 1. Sakarya S, Gunay N, Karakulak M, Ozturk B, Ertugrul B. Hypochlorous acid: an ideal wound care agent with powerful microbicidal, antibiofilm, and wound healing potency. Wounds. 2014;26(12):342–350.
2. Hidalgo E, Bartolome R, Dominguez C. Cytotoxicity mechanisms of sodium hypochlorite in cultured human dermal fibroblasts and its bactericidal effectiveness. Chem Biol Interact. 2002;139(3):265-282. doi:10.1016/s0009-2797(02)00003-0
3. Wang L, Bassir M, Najafi R, Najafi K, Yang J, Khosrovi B, Hwong W, Barati E, Beslisle B, Celeri C, Robson MC. Hyphochlorous acid as a potential wound care agent: Part I: Stabilized hypochlorous acid: a component of the inorganic armamentarium of innate immunity. J Burns Wounds 2007 Apr 11;6:e5.
4. R. Matthews, M. , N. Quan, A. , R. Shah, A. , I. Tugulan, C. , A. Nashed, B. , F. Goldberg, R. , G. Pieri, P. , G. Fernandez, L. , Kowal-Vern, A. and N. Foster, K. (2018) Hypochlorous Acid for Septic Abdominal Processes Using a Unique Negative Pressure Wound Therapy System: A Pilot Study. Surgical Science, 9, 412-421. doi: 10.4236/ss.2018.911048.
5. Luis G Fern√°ndez LG, Matthews, MR Seal L. Intraabdominal Lavage of Hypochlorous Acid: A New Paradigm for the Septic and Open Abdomen. Wounds 2020; 32 (4): 107-114 Epub 2020 January 23
6. Aderem A, Phagocytosis and the Inflammatory Response, The Journal of Infectious Diseases, Volume 187, Issue Supplement_2, June 2003, Pages S340–5, https://doi.org/10.1086/3747477.
7. Garin J, Diez R, Kieffer S, Dermine JF, Duclos S, Gagnon E, Sadoul R, Rondeau C, Desjardins M.J. The Phagosome Proteome: Insight Into Phagosome Functions Cell Biol. 2001 Jan 8; 152(1):165-80.
8. Armstrong, DG, Bohn G, Glat, P, Kavros, SJ, Kirsner, R, Snyder, R, Tettelbach, W.: Expert Recommendations for the use of hypochlorous solution: science and clinical application. Wounds May 2015.
9. Chen Y, Junger WG. Measurement of oxidative burst in neutrophils. Methods Mol Biol. 2012; 844:115–124.
10. Gethin, G.: The Significance of Surface pH in Chronic Wounds. Wounds UK, vol. 3, No. 3, pg. 52, 2007.
11. Shi L, Ramsay S, Ermis R. and Carson D.: pH in the Bacteria-Contaminated Wound and Its Impact on Clostridium histolyticum Collagenase Activity: Implications for the Use of Collagenase Wound Debridement Agents. J Wound Ostomy Continence Nurs. 2011;38(5):514.
12. Nagoba BS, Suryawanshi NM, Wadher B, Selkar S. Acidic Environment and Wound Healing: A Review, Wounds. 2015;27(1):5-11.
13. Shukla VK, Shukla D, Tiwary SK, Agrawal S, Rastogi A. Evaluation of pH measurement as a method of wound assessment. Wound Care 2007, vol.16 (7): 291S.
14. Sharpe JR, Simon Booth,Kasia Jubin,Nigel R. Jordan, Diana J. Lawrence-Watt, Baljit S. Dheansa,. Progression of wound pH during the course of healing in burns. J Burn Care Res. 2013, vol. 34(3), e201.
15. Fernandez L, Ellman C, Jackson P. Initial Experience Using a Novel Reticulated Open Cell Foam Dressing with Through Holes during Negative Pressure Wound Therapy with Instillation for Management of Pressure Ulcers. J Trauma Treat. 2017; 6:410.
16. White GC, “Handbook of Chlorination and alternative disinfectants.” 4th Edition, 1999, Wiley Interscience, p.215 - 219
17. European Union Risk Assessment Report, Sodium Hypochlorite, 2007, p.20