title: Effect of non-steroidal anti-inflammatory drugs on biological properties of Acanthamoeba castellanii belonging to the T4 genotype.
abstract: Non-steroidal anti-inflammatory drug, Diclofenac, targeting COX have shown promise in the treatment of Acanthamoeba keratitis, but the underlying mechanisms remain unknown. Using various NSAIDs, Diclofenac sodium, Indomethacin, and Acetaminophen, here we determined the effects of NSAIDs on the biological properties of Acanthamoeba castellanii belonging to the T4 genotype. Using amoebicidal assays, the results revealed that Diclofenac sodium, and Indomethacin affected growth of A. castellanii. In contrast, none of the compounds tested had any effect on the viability of A. castellanii. Importantly, all NSAIDs tested abolished A. castellanii encystation. This is a significant finding as the ability of amoebae to transform into the dormant cyst form presents a significant challenge in the successful treatment of infection. The NSAIDs inhibit production of cyclo-oxegenase, which regulates the synthesis of prostaglandins suggesting that cyclooxygenases (COX-1 and COX-2) and prostaglandins play significant role(s) in Acanthamoeba biology. As NSAIDs are routinely used in the clinical practice, these findings may help design improved preventative strategies and/or of therapeutic value to improve prognosis, when used in combination with other anti-amoebic drugs.
authors.affiliation: Department of Biological Sciences, Faculty of Science and Technology, Sunway University, Selangor, Malaysia.
authors.forename: Ruqaiyyah
authors.initials: R
authors.lastname: Siddiqui
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Sahreena
authors.initials: S
authors.lastname: Lakhundi
authors.affiliation: Division of Pediatric Infectious Diseases, Vanderbilt University School of Medicine, Nashville, USA.
authors.forename: Junaid
authors.initials: J
authors.lastname: Iqbal
authors.affiliation: Department of Biological Sciences, Faculty of Science and Technology, Sunway University, Selangor, Malaysia. Electronic address: naveed5438@gmail.com.
authors.forename: Naveed Ahmed
authors.initials: NA
authors.lastname: Khan
mesh_terms: D015823:Acanthamoeba Keratitis / Q000188:drug therapy / Q000469:parasitology; D048248:Acanthamoeba castellanii / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D000082:Acetaminophen / Q000494:pharmacology; D000563:Amebicides / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology; D005838:Genotype; D007213:Indomethacin / Q000494:pharmacology; D000069289:Parasite Encystment / Q000187:drug effects; D011453:Prostaglandins / Q000378:metabolism
chemical_list: D000563:Amebicides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D004008:Diclofenac; D000082:Acetaminophen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D007213:Indomethacin
keywords: Acanthamoeba; Amoebicidal; Amoebistatic; Encystation; Non-steroidal anti-inflammatory drugs