The effects of oral antihistamines on the formation of granulation tissue on full-thickness wounds in white rats Rattus norvegicus

Taufiqur Rakhim Aditra; Agus Santoso Budi; Iswinarno Dos Saputro

doi:10.15562/bmj.v11i3.3928

The effects of oral antihistamines on the formation of granulation tissue on full-thickness wounds in white rats Rattus norvegicus

Taufiqur Rakhim Aditra ,

Agus Santoso Budi ,

Iswinarno Doso Saputro ,

pdf |
DOI: https://doi.org/10.15562/bmj.v11i3.3928 |
Published: 2022-12-20

Abstract

Background: Granulation tissue is formed during the proliferative phase of wound healing. In the presence of granulation tissue, the process of epithelialization can take place. Disturbance in the formation of granulation tissue, especially hyper-granulation, will result in an abnormal wound healing process. Antihistamines have been shown to have an effect on abnormal wound tissue fibroblasts and reduce collagen synthesis both by topical administration in vivo and in vitro culture. This study aimed to investigate the effect of oral antihistamines on granulation tissue formation, collagen deposition, and angiogenesis involved.

Method: The study design used was an experimental randomized post-test only. Thirty-two rats were divided into 2 groups, wherein group 1 was treated as a control while those in the second group were given oral diphenhydramine with a dose according to body weight. Full-thickness wounds were made on the back of all rats. The treatment was carried out every day for 7 days. On the 7^th day, granulation tissue specimens were taken with an excisional biopsy from the wound. From each granulation tissue sample, data taken were the granulation tissue thickness, collagen density, and the number of capillaries formed.

Results: Using an independent T-test, the mean thickness of granulation tissue in the treatment group was significantly smaller than the control group (215.82 ± 44.73 μm vs. 304.43 ± 58.61 μm, p<0.005). Mann-Whitney test revealed that the mean number of capillaries in the treatment group was significantly less than the control group (38.11 ± 5.31 vs. 69.66 ± 11.81, p<0.005). Kruskal-Wallis test revealed that the collagen density of the treatment group was significantly smaller than the control group (p<0.0001).

Conclusion: Administration of oral antihistamines can inhibit the formation of granulation tissue in full-thickness wounds and also reduce collagen density and angiogenesis. This can serve as a reference for the effect of oral antihistamines on wound healing, especially in the process of granulation tissue formation.

References

Vuolo J. Hypergranulation: exploring possible management options. Br J Nurs. 2010;19(6):S4-S8. doi:10.12968/bjon.2010.19.Sup2.47244.
Häkkinen L, Larjava H, Koivisto L. Granulation tissue formation and remodeling. Endod Top. 2011;24(1):94–129. https://doi.org/10.1111/etp.12008.
Hutagalung M, Perdanakusuma D, Wulandari P. Effect of Topical H1-antihistamine on the level of Transforming growth factor beta (TGF-β) and Collagen of Acute wound in animal model. Res J Pharm Technol [Internet]. 2022;15(8). https://doi.org/10.52711/0974-360X.2022.00597.
Zheng M, Wang C. Chlorpheniramine maleate exerts an anti-keloid activity in vivo and in vitro. 2022;1–23. https://doi.org/10.21203/rs.3.rs-1221237/v1.
Numata Y, Terui T, Okuyama R, et al. The accelerating effect of histamine on the cutaneous wound-healing process through the action of basic fibroblast growth factor. J Invest Dermatol. 2006;126(6):1403-1409. doi:10.1038/sj.jid.5700253.
Kwa KAA, Pijpe A, Middelkoop E, van Baar ME, Niemeijer AS, Breederveld RS, et al. Comparing doxepin cream to oral antihistamines for the treatment of itch in burn patients: A multi-center triple-blind randomized controlled trial. Burn Open. 2019;3(4):135–40. https://doi.org/10.1016/j.burnso.2019.07.003.
McShane DB, Bellet JS. Treatment of hyper granulation tissue with high potency topical corticosteroids in children. Pediatr Dermatol. 2012;29(5):675–8. https://doi.org/10.1111/j.1525-1470.2012.01724.x.
Jaeger M, Harats M, Kornhaber R, Aviv U, Zerach A, Haik J. Treatment of hyper granulation tissue in burn wounds with topical steroid dressings: A case series. Int Med Case Rep J. 2016;9:241–5. https://doi.org/10.2147/IMCRJ.S113182.
Wolak M, Bojanowska E, Staszewska T, Piera L, Szymański J, Drobnik J. Histamine augments collagen content via H1 receptor stimulation in cultures of myofibroblasts taken from wound granulation tissue. Mol Cell Biochem. 2021;476(2):1083-1092. doi:10.1007/s11010-020-03974-6.
Leoncini E, Ricciardi W, Cadoni G, Arzani D, Petrelli L, Paludetti G, et al. Adult height and head and neck cancer: A pooled analysis within the INHANCE Consortium. Head Neck. 2014;36(10):1391. https://doi.org/10.1002/HED.
Murota H, Bae S, Hamasaki Y, Maruyama R, Katayama I. Emedastine difumarate inhibits histamine-induced collagen synthesis in dermal fibroblasts [published correction appears in J Investig Allergol Clin Immunol. 2009;19(2):166. Dosage error in article text]. J Investig Allergol Clin Immunol. 2008;18(4):245-252.
Horie M, Saito A, Yamauchi Y, et al. Histamine induces human lung fibroblast-mediated collagen gel contraction via histamine H1 receptor. Exp Lung Res. 2014;40(5):222-236. doi:10.3109/01902148.2014.900155.
Piera L, Olczak S, Kun T, et al. Disruption of histamine/H3 receptor signal reduces collagen deposition in cultures scar myofibroblasts. J Physiol Pharmacol. 2019;70(2):10.26402/jpp.2019.2.07. doi:10.26402/jpp.2019.2.07.
Takeda T, Goto H, Arisawa T, Hase S, Hayakawa T, Asai J. Effect of histamine on human fibroblast in vitro. Arzneimittelforschung. 1997;47(10):1152-1155.
Piera L, Szymański J, Juszczak M, Drobnik J. Histamine is involved in the regulation of collagen content in cultured heart myofibroblasts via H2, H3 and H4 histamine receptors. Biomed Rep. 2021;15(2):71. doi:10.3892/br.2021.1447.

[1] Vuolo J. Hypergranulation: exploring possible management options. Br J Nurs. 2010;19(6):S4-S8. doi:10.12968/bjon.2010.19.Sup2.47244.

[2] Häkkinen L, Larjava H, Koivisto L. Granulation tissue formation and remodeling. Endod Top. 2011;24(1):94–129. https://doi.org/10.1111/etp.12008.

[3] Hutagalung M, Perdanakusuma D, Wulandari P. Effect of Topical H1-antihistamine on the level of Transforming growth factor beta (TGF-β) and Collagen of Acute wound in animal model. Res J Pharm Technol [Internet]. 2022;15(8). https://doi.org/10.52711/0974-360X.2022.00597.

[4] Zheng M, Wang C. Chlorpheniramine maleate exerts an anti-keloid activity in vivo and in vitro. 2022;1–23. https://doi.org/10.21203/rs.3.rs-1221237/v1.

[5] Numata Y, Terui T, Okuyama R, et al. The accelerating effect of histamine on the cutaneous wound-healing process through the action of basic fibroblast growth factor. J Invest Dermatol. 2006;126(6):1403-1409. doi:10.1038/sj.jid.5700253.

[6] Kwa KAA, Pijpe A, Middelkoop E, van Baar ME, Niemeijer AS, Breederveld RS, et al. Comparing doxepin cream to oral antihistamines for the treatment of itch in burn patients: A multi-center triple-blind randomized controlled trial. Burn Open. 2019;3(4):135–40. https://doi.org/10.1016/j.burnso.2019.07.003.

[7] McShane DB, Bellet JS. Treatment of hyper granulation tissue with high potency topical corticosteroids in children. Pediatr Dermatol. 2012;29(5):675–8. https://doi.org/10.1111/j.1525-1470.2012.01724.x.

[8] Jaeger M, Harats M, Kornhaber R, Aviv U, Zerach A, Haik J. Treatment of hyper granulation tissue in burn wounds with topical steroid dressings: A case series. Int Med Case Rep J. 2016;9:241–5. https://doi.org/10.2147/IMCRJ.S113182.

[9] Wolak M, Bojanowska E, Staszewska T, Piera L, Szymański J, Drobnik J. Histamine augments collagen content via H1 receptor stimulation in cultures of myofibroblasts taken from wound granulation tissue. Mol Cell Biochem. 2021;476(2):1083-1092. doi:10.1007/s11010-020-03974-6.

[10] Leoncini E, Ricciardi W, Cadoni G, Arzani D, Petrelli L, Paludetti G, et al. Adult height and head and neck cancer: A pooled analysis within the INHANCE Consortium. Head Neck. 2014;36(10):1391. https://doi.org/10.1002/HED.

[11] Murota H, Bae S, Hamasaki Y, Maruyama R, Katayama I. Emedastine difumarate inhibits histamine-induced collagen synthesis in dermal fibroblasts [published correction appears in J Investig Allergol Clin Immunol. 2009;19(2):166. Dosage error in article text]. J Investig Allergol Clin Immunol. 2008;18(4):245-252.

[12] Horie M, Saito A, Yamauchi Y, et al. Histamine induces human lung fibroblast-mediated collagen gel contraction via histamine H1 receptor. Exp Lung Res. 2014;40(5):222-236. doi:10.3109/01902148.2014.900155.

[13] Piera L, Olczak S, Kun T, et al. Disruption of histamine/H3 receptor signal reduces collagen deposition in cultures scar myofibroblasts. J Physiol Pharmacol. 2019;70(2):10.26402/jpp.2019.2.07. doi:10.26402/jpp.2019.2.07.

[14] Takeda T, Goto H, Arisawa T, Hase S, Hayakawa T, Asai J. Effect of histamine on human fibroblast in vitro. Arzneimittelforschung. 1997;47(10):1152-1155.

[15] Piera L, Szymański J, Juszczak M, Drobnik J. Histamine is involved in the regulation of collagen content in cultured heart myofibroblasts via H2, H3 and H4 histamine receptors. Biomed Rep. 2021;15(2):71. doi:10.3892/br.2021.1447.

The effects of oral antihistamines on the formation of granulation tissue on full-thickness wounds in white rats Rattus norvegicus

Abstract

References

How to Cite

Search Panel