TY - JOUR

T1 - Features of the response to subchronic low-dose exposure to copper oxide nanoparticles in rats

AU - Sutunkova, Marina

AU - Ryabova, Yuliya

AU - Minigalieva, Ilzira

AU - Bushueva, Tatiana

AU - Sakhautdinova, Renata

AU - Bereza, Ivan A.

AU - Shaikhova, Daria

AU - Amromina, Anna M.

AU - Chemezov, Aleksei I.

AU - Shelomencev, Ivan

AU - Amromin, Lev

AU - Valamina, Irene

AU - Toropova, Liubov

N1 - Open Access funding enabled and organized by Projekt DEAL. The research funding from Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers for funding the experimental materials and facilities is gratefully acknowledged. The research funding from the Ministry of Science and Higher Education of the Russian Federation (Ural Federal University Program of Development within the Priority–2030 Program) for experiment implementation and analysis of its results is gratefully acknowledged. The authors would like to express their deepest gratitude to the staff of the Ural Center for Shared Use “Modern Nanotechnologies” of the Ural Federal University named after the First Russian President Boris Yeltsin and personally to Professor Vladimir Ya. Shur, Director of the Center, for invaluable support in conducting this study by synthesizing suspensions of the nanoparticles studied. We are also grateful to the staff of the Central Research Laboratory of the Ural State Medical University and personally to Professor Oleg G. Makeyev for establishing genomic DNA fragmentation.

PY - 2023

Y1 - 2023

N2 - Copper is an essential trace element for human health and, at the same time, a major industrial metal widely used both in its elemental form and in compounds. We conducted a dose-dependent assessment of the response of outbred albino male rats to subchronic low-dose exposure to copper oxide nanoparticles administered intraperitoneally at cumulative doses of 18 and 36 mg/kg during 6 weeks to exposure groups 1 and 2, respectively. We observed disorders at different levels of organization of the body in the exposed animals, from molecular to organismal. The observed decrease in the activity of succinate dehydrogenase in nucleated blood cells gave evidence of impaired bioenergetics processes. In view of the results of the metabolomics analysis, we assume mitochondrial damage and contribution of apoptotic processes to the pathology induced by copper poisoning. We also assume neurodegenerative effects based on the assessed morphological parameters of the nervous system, results of behavioral tests, and a decreased level of expression of genes encoding NMDA receptor subunits in the hippocampus. The hepatotoxic effect noted by a number of metabolomics-based, biochemical, and cytological indicators was manifested by the impaired protein-synthesizing function of the liver and enhanced degenerative processes in its cells. We also observed a nephrotoxic effect of nanosized copper oxide with a predominant lesion of proximal kidney tubules. At the same time, both doses tested demonstrated such positive health effects as a statistically significant decrease in the activity of alkaline phosphatase and the nucleated blood cell DNA fragmentation factor. Judging by the changes observed, the cumulative dose of copper oxide nanoparticles of 18 mg/kg body weight administered intraperitoneally approximates the threshold one for rats. The established markers of health impairments may serve as a starting point in the development of techniques of early diagnosis of copper poisoning.

AB - Copper is an essential trace element for human health and, at the same time, a major industrial metal widely used both in its elemental form and in compounds. We conducted a dose-dependent assessment of the response of outbred albino male rats to subchronic low-dose exposure to copper oxide nanoparticles administered intraperitoneally at cumulative doses of 18 and 36 mg/kg during 6 weeks to exposure groups 1 and 2, respectively. We observed disorders at different levels of organization of the body in the exposed animals, from molecular to organismal. The observed decrease in the activity of succinate dehydrogenase in nucleated blood cells gave evidence of impaired bioenergetics processes. In view of the results of the metabolomics analysis, we assume mitochondrial damage and contribution of apoptotic processes to the pathology induced by copper poisoning. We also assume neurodegenerative effects based on the assessed morphological parameters of the nervous system, results of behavioral tests, and a decreased level of expression of genes encoding NMDA receptor subunits in the hippocampus. The hepatotoxic effect noted by a number of metabolomics-based, biochemical, and cytological indicators was manifested by the impaired protein-synthesizing function of the liver and enhanced degenerative processes in its cells. We also observed a nephrotoxic effect of nanosized copper oxide with a predominant lesion of proximal kidney tubules. At the same time, both doses tested demonstrated such positive health effects as a statistically significant decrease in the activity of alkaline phosphatase and the nucleated blood cell DNA fragmentation factor. Judging by the changes observed, the cumulative dose of copper oxide nanoparticles of 18 mg/kg body weight administered intraperitoneally approximates the threshold one for rats. The established markers of health impairments may serve as a starting point in the development of techniques of early diagnosis of copper poisoning.

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UR - https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=tsmetrics&SrcApp=tsm_test&DestApp=WOS_CPL&DestLinkType=FullRecord&KeyUT=001034811000009

U2 - 10.1038/s41598-023-38976-z

DO - 10.1038/s41598-023-38976-z

M3 - Article

VL - 13

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 11890

ER -