Siddiqui Ruqaiyyah, Lakhundi Sahreena, Iqbal Junaid, Khan Naveed Ahmed
Department of Biological Sciences, Faculty of Science and Technology, Sunway University, Selangor, Malaysia.
Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
Exp Parasitol. 2016 Sep;168:45-50. doi: 10.1016/j.exppara.2016.06.011. Epub 2016 Jul 2.
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.
靶向环氧化酶（COX）的非甾体抗炎药双氯芬酸在棘阿米巴角膜炎治疗中显示出前景，但潜在机制仍不明。我们使用双氯芬酸钠、吲哚美辛和对乙酰氨基酚等多种非甾体抗炎药，测定了这些非甾体抗炎药对属于T4基因型的卡氏棘阿米巴生物学特性的影响。通过杀阿米巴试验，结果显示双氯芬酸钠和吲哚美辛影响卡氏棘阿米巴的生长。相比之下，所测试的化合物均对卡氏棘阿米巴的活力无任何影响。重要的是，所有测试的非甾体抗炎药均消除了卡氏棘阿米巴的包囊形成。这是一个重要发现，因为阿米巴转化为休眠包囊形式的能力在成功治疗感染方面构成了重大挑战。非甾体抗炎药抑制环氧化酶的产生，而环氧化酶调节前列腺素的合成，这表明环氧化酶（COX - 1和COX - 2）和前列腺素在棘阿米巴生物学中发挥重要作用。由于非甾体抗炎药在临床实践中经常使用，这些发现可能有助于设计改进的预防策略和/或具有治疗价值，以便在与其他抗阿米巴药物联合使用时改善预后。
