Editing Metronidazole (section)

==Research==
Metronidazole is researched for its anti-inflammatory and immunomodulatory properties. Studies have shown that metronidazole can decrease the production of [[reactive oxygen species]] (ROS) and [[nitric oxide]] by activated immune cells, such as [[macrophage]]s and [[neutrophil]]s. Metronidazole's [[Immunity (medical)|immunomodulatory]] properties are thought to be related to its ability to decrease the activation of [[nuclear factor-kappa B]] (NF-κB), a [[transcription factor]] that regulates the expression of [[Inflammatory cytokine|pro-inflammatory]] [[cytokine]]s, including [[chemokine]]s, and [[Cell adhesion molecule|adhesion molecules]]. Cytokines are small proteins that are secreted by immune cells and play a key role in the immune response.<ref name="pmid10767254">{{cite journal |vauthors=Opal SM, DePalo VA |title=Anti-inflammatory cytokines |journal=Chest |volume=117 |issue=4 |pages=1162–72 |date=April 2000 |pmid=10767254 |doi=10.1378/chest.117.4.1162 |s2cid=2267250 |url=}}</ref> Chemokines are a type of cytokines that act as chemoattractants, meaning they attract and guide immune cells to specific sites in the body where they are needed.<ref name="pmid26490276">{{cite journal |vauthors=van der Vorst EP, Döring Y, Weber C |title=Chemokines |journal=Arterioscler Thromb Vasc Biol |volume=35 |issue=11 |pages=e52–6 |date=November 2015 |pmid=26490276 |doi=10.1161/ATVBAHA.115.306359 |url=|doi-access=free }}</ref> Cell adhesion molecules play an important role in the immune response by facilitating the interaction between immune cells and other cells in the body, such as endothelial cells, which form the lining of blood vessels.<ref name="pmid9150551">{{cite journal |vauthors=Elangbam CS, Qualls CW, Dahlgren RR |title=Cell adhesion molecules--update |journal=Vet Pathol |volume=34 |issue=1 |pages=61–73 |date=January 1997 |pmid=9150551 |doi=10.1177/030098589703400113 |s2cid=46474241 |url=}}</ref> By inhibiting NF-κB activation, metronidazole can reduce the production of pro-inflammatory cytokines, such as [[Tumor necrosis factor-alpha|TNF-alpha]], [[Interleukin 6|IL-6]], and [[Interleukin 1 beta|IL-1β]].<ref name="pmid20399284">{{cite journal |vauthors=Rizzo A, Paolillo R, Guida L, Annunziata M, Bevilacqua N, Tufano MA |title=Effect of metronidazole and modulation of cytokine production on human periodontal ligament cells |journal=Int Immunopharmacol |volume=10 |issue=7 |pages=744–50 |date=July 2010 |pmid=20399284 |doi=10.1016/j.intimp.2010.04.004 |url=}}</ref>

Metronidazole has been studied in various immunological disorders, including [[inflammatory bowel disease]], [[Periodontal disease|periodontitis]], and [[rosacea]]. In these conditions, metronidazole has been suspected to have anti-inflammatory and immunomodulatory effects that could be beneficial in the treatment of these conditions.<ref name="pmid37295025">{{cite journal |vauthors=Gonçalves-Santos E, Caldas I, Fernandes V, Franco L, Pelozo M, Feltrim F, Maciel J, Machado J, Gonçalves R, Novaes R |title=Pharmacological potential of new metronidazole/eugenol/dihydroeugenol hybrids against Trypanosoma cruzi in vitro and in vivo |journal=Int Immunopharmacol |volume=121 |issue= |pages=110416 |date=August 2023 |pmid=37295025 |doi=10.1016/j.intimp.2023.110416 |s2cid=259126738 |url=}}</ref> Despite the success in treating rosacea with metronidazole,<ref name="pmid37550898">{{cite journal |vauthors=King S, Campbell J, Rowe R, Daly ML, Moncrieff G, Maybury C |title=A systematic review to evaluate the efficacy of azelaic acid in the management of acne, rosacea, melasma and skin aging |journal=J Cosmet Dermatol |volume=22 |issue=10 |pages=2650–2662 |date=October 2023 |pmid=37550898 |doi=10.1111/jocd.15923 |s2cid=260701677 |url=|doi-access=free }}</ref><ref name="pmid37591279">{{cite journal |vauthors=Kazemi S, Hawkes JE |title=Ocular rosacea associated with transient monocular vision loss: resolution with oral metronidazole |journal=Dermatol Online J |volume=29 |issue=3 |pages= |date=June 2023 |pmid=37591279 |doi=10.5070/D329361439 |s2cid=263745257 |url=https://escholarship.org/content/qt9zz9v05q/qt9zz9v05q.pdf?t=rxxvc4 |doi-access=free |access-date=2 February 2024 |archive-date=2 February 2024 |archive-url=https://web.archive.org/web/20240202143841/https://escholarship.org/content/qt9zz9v05q/qt9zz9v05q.pdf?t=rxxvc4 |url-status=live }}</ref><ref name="pmid36478427">{{cite journal |vauthors=Kim JS, Seo BH, Cha DR, Suh HS, Choi YS |title=Maintenance of Remission after Oral Metronidazole Add-on Therapy in Rosacea Treatment: A Retrospective, Comparative Study |journal=Ann Dermatol |volume=34 |issue=6 |pages=451–460 |date=December 2022 |pmid=36478427 |pmc=9763916 |doi=10.5021/ad.22.093 |url=}}</ref><ref name="pmid36177741">{{cite journal |vauthors=Yamasaki K, Miyachi Y |title=Perspectives on rosacea patient characteristics and quality of life using baseline data from a phase 3 clinical study conducted in Japan |journal=J Dermatol |volume=49 |issue=12 |pages=1221–1227 |date=December 2022 |pmid=36177741 |pmc=10092295 |doi=10.1111/1346-8138.16596 |url=}}</ref><ref name="pmid36330970">{{cite journal |vauthors=Dall'Oglio F, Nasca MR, Gerbino C, Micali G |title=Advances in pharmacotherapy for rosacea: what is the current state of the art? |journal=Expert Opin Pharmacother |volume=23 |issue=16 |pages=1845–1854 |date=November 2022 |pmid=36330970 |doi=10.1080/14656566.2022.2142907 |s2cid=253301872 |url=}}</ref> the exact mechanism of why metronidazole in rosacea is efficient is not precisely known, i.e., which properties of metronidazole help treat rosacea: antibacterial or immunomodulatory or both, or other mechanism is involved.<ref name="pmid32362310">{{cite journal |vauthors=Seidler Stangova P, Dusek O, Klimova A, Heissigerova J, Kucera T, Svozilkova P |title=Metronidazole Attenuates the Intensity of Inflammation in Experimental Autoimmune Uveitis |journal=Folia Biol (Praha) |volume=65 |issue=5–6 |pages=265–274 |date=2019 |pmid=32362310 |doi= 10.14712/fb2019065050265|s2cid=218491876 |url=|doi-access=free }}</ref><ref name="pmid18182250">{{cite journal |vauthors=Fararjeh M, Mohammad MK, Bustanji Y, Alkhatib H, Abdalla S |title=Evaluation of immunosuppression induced by metronidazole in Balb/c mice and human peripheral blood lymphocytes |journal=Int Immunopharmacol |volume=8 |issue=2 |pages=341–50 |date=February 2008 |pmid=18182250 |doi=10.1016/j.intimp.2007.10.018 |url=}}</ref> Increased [[Reactive oxygen species|ROS]] production in rosacea is thought to contribute to the inflammatory process and skin damage, so metronidazole's ability to decrease ROS may explain the mechanism of action in this disease, but this remains speculation.<ref name="pmid15499754">{{cite journal |vauthors=Jones D |title=Reactive oxygen species and rosacea |journal=Cutis |volume=74 |issue=3 Suppl |pages=17–20, 32–4 |date=September 2004 |pmid=15499754 |doi= |url=}}</ref><ref name="pmid17725855">{{cite journal |vauthors=Narayanan S, Hünerbein A, Getie M, Jäckel A, Neubert RH |title=Scavenging properties of metronidazole on free oxygen radicals in a skin lipid model system |journal=J Pharm Pharmacol |volume=59 |issue=8 |pages=1125–30 |date=August 2007 |pmid=17725855 |doi=10.1211/jpp.59.8.0010 |s2cid=19772010 |url=|doi-access=free }}</ref>

Metronidazole is also researched as a potential anti-inflammatory agent in [[periodontitis]] treatment.<ref name="pmid38613247">{{cite journal |vauthors=Suárez LJ, Arce RM, Gonçalves C, Furquim CP, Santos NC, Retamal-Valdes B, Feres M |title=Metronidazole may display anti-inflammatory features in periodontitis treatment: A scoping review |journal=Mol Oral Microbiol |volume= 39|issue= 4|pages= 240–259|date=April 2024 |pmid=38613247 |doi=10.1111/omi.12459}}</ref>