International Journal of Environmental Research and Public Health Article Polystyrene Microplastics Exposure: An Insight into Multiple Organ Histological Alterations, Oxidative Stress and Neurotoxicity in Javanese Medaka Fish (Oryzias javanicus Bleeker, 1854) Sunusi Usman 1 , Ahmad Faizal Abdull Razis 1,2, * , Khozirah Shaari 1,3 , Mohammad Noor Azmai Amal 4,5 , Mohd Zamri Saad 5,6 , Nurulfiza Mat Isa 7,8 and Muhammad Farhan Nazarudin 5   Citation: Usman, S.; Abdull Razis, A.F.; Shaari, K.; Amal, M.N.A.; Saad, M.Z.; Mat Isa, N.; Nazarudin, M.F. Polystyrene Microplastics Exposure: An Insight into Multiple Organ Histological Alterations, Oxidative Stress and Neurotoxicity in Javanese Medaka Fish (Oryzias javanicus Bleeker, 1854). Int. J. Environ. Res. Public Health 2021, 18, 9449. https:// doi.org/10.3390/ijerph18189449 Academic Editors: Angela Di Pietro and Paul B. Tchounwou Received: 7 July 2021 Accepted: 3 September 2021 Published: 7 September 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia; usunusi.bch@buk.edu.ng (S.U.); khozirah@upm.edu.my (K.S.) 2 Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia 3 Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia 4 Department of Biology, Faculty of Science, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia; mnamal@upm.edu.my 5 Aquatic Animal Health and Therapeutics Laboratory (Aqua Health), Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia; mzamri@upm.edu.my (M.Z.S.); m_farhannaza@upm.edu.my (M.F.N.) 6 Department of Veterinary Laboratory Diagnosis, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia 7 Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia; nurulfiza@upm.edu.my 8 Laboratory of Vaccines and Biomolecules (VacBio), Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia * Correspondence: madfaizal@upm.edu.my; Tel.: +60-111-566-2667 Abstract: Microplastics (MPs) have become pollutants of concern due to their unknown human health effect and negative impact on terrestrial and aquatic ecosystems. There is increasing number of experimental research on MPs globally with its effects not fully understood; recent animal studies explore its effects on the intestines, yet on other vital organs. Javanese medaka fish was exposed to polystyrene microplastics (PS-MPs) beads for a period of 21 days. Histological alterations, intestinal oxidative stress, permeability and neurotoxicity were evaluated. Significant inflammatory changes and tissue damage were observed in the intestine, liver and kidney. Intestinal oxidative stress and permeability were found to be significantly increased. In the brain, neurotoxicity characterised by a significant induction of oxidative stress, lipid peroxidation and the inhibition of acetylcholinesterase enzyme were elucidated. This study provided an insight into the multiple organ effect of microplas- tics exposure, necessitating further exploration and identification of biomarkers to be utilised for biomonitoring population at risk in the future. Keywords: polystyrene microplastics; histological alterations; oxidative stress; neurotoxicity; Javanese medaka fish 1. Introduction Plastics versatility, light weight and the low cost of production have made them invaluable in our society, thus fuelling their global demand [1]. Plastic production has dramatically risen worldwide [2]. As of 2019, stood at 368 million metric tons (MT), with the figure expected to double in the next 20 years. Coastal countries generate about 275 million MT of plastics out of which 4.8 to 12.7 enter the ocean [3]. MPs synthesised primarily in micro-sized form (5 μm or less), and those emanating from the degradation of larger plastics are mostly discharged into the aquatic environment due to indiscriminate disposal Int. J. Environ. Res. Public Health 2021, 18, 9449. https://doi.org/10.3390/ijerph18189449 https://www.mdpi.com/journal/ijerph