title: Copper(II) oxide nanoparticles augment antifilarial activity of Albendazole: In vitro synergistic apoptotic impact against filarial parasite Setaria cervi.
abstract: Mass treatment of lymphatic filariasis with Albendazole (ABZ), a therapeutic benzimidazole, is fraught with serious limitations such as possible drug resistance and poor macrofilaricidal activity. Therefore, we need to develop new ABZ-based formulations to improve its antifilarial effectiveness. CuO nanoparticles were used as an adjuvant with ABZ to form ABZ-CuO nanocomposite, which was characterized by UV-vis spectroscopy, FT-IR, AFM and SEM. Antifilarial activity of nanocomposite was evaluated using relative motility assay and dye exclusion test in dark and under UV light. ROS generation, antioxidant levels, lipid peroxidation and DNA fragmentation in nanocomposite treated parasites were estimated. Biophysical techniques were employed to ascertain the mode of binding of nanocomposite to parasitic DNA. Nanocomposite increases parasite mortality as compared to ABZ in dark, and its antifilarial effect was increased further under UV light. Elevated ROS production and decline of parasitic-GST and GSH levels were observed in nanocomposite treated worms in dark, and these effects were pronounced further under UV light. Nanocomposite leads to higher DNA fragmentation as compared to ABZ alone. Further, we found that nanocomposite binds parasitic DNA in an intercalative manner where it generates ROS to induce DNA damage. Thus, oxidative stress production due to ROS generation and consequent DNA fragmentation leads to apoptosis in worms. This is the first report supporting CuO nanoparticles as a potential adjuvant with ABZ against filariasis along with enhanced antifilarial activity of nanocomposite under UV light. These findings, thus, indicate that development of ABZ-loaded nanoparticle compounds may serve as promising leads for filariasis treatment.
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.
authors.forename: Atif
authors.initials: A
authors.lastname: Zafar
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.
authors.forename: Irshad
authors.initials: I
authors.lastname: Ahmad
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.
authors.forename: Ajaz
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India. Electronic address: masood_amua@yahoo.co.in.
authors.forename: Masood
authors.initials: M
authors.lastname: Ahmad
mesh_terms: D015766:Albendazole / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000969:Antinematodal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D020552:Comet Assay; D003300:Copper / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D053938:DNA Fragmentation; D018509:DNA, Helminth / Q000187:drug effects / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D053761:Nanocomposites / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D009348:Nematoda / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D000969:Antinematodal Agents; D018509:DNA, Helminth; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D017665:Hydroxyl Radical; D003300:Copper; D015766:Albendazole; C030973:cupric oxide
keywords: ABZ-CuO nanocomposite; Albendazole (PubChem CID: 2082); Apoptosis; DNA damage; Ethidium bromide (PubChem CID: 14710); Glutathione (PubChem CID: 124886); Lymphatic filariasis; Nanoparticles; Potassium iodide (PubChem CID: 4875); Trypan blue (PubChem CID: 49859753); Urea (PubChem CID: 1176)