Hepato-renal toxicity of oral sub-chronic exposure to aluminum oxide and/or zinc oxide nanoparticles in rats

Mokhtar Ibrahim Yousef; Thulfiqar Fawwaz Mutar; Maher Abd El-Nabi Kamel

doi:10.1016/j.toxrep.2019.04.003

Hepato-renal toxicity of oral sub-chronic exposure to aluminum oxide and/or zinc oxide nanoparticles in rats

Toxicol Rep. 2019 Apr 19:6:336-346. doi: 10.1016/j.toxrep.2019.04.003. eCollection 2019.

Authors

Mokhtar Ibrahim Yousef¹, Thulfiqar Fawwaz Mutar¹, Maher Abd El-Nabi Kamel²

Affiliations

¹ Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Egypt.
² Department of Biochemistry, Medical Research Institute, Alexandria University, Egypt.

Abstract

Aluminum oxide nanoparticles (Al₂O₃NPs) and zinc oxide nanoparticles (ZnONPs) have been involved in many industries and they are extensively abundant in many aspects of human life. Consequently, concerns have been raised about their potentially harmful effects. However the toxicities of Al₂O₃NPs and ZnONPs are well documented, the effect of co-exposure to both nanoparticles remains strictly obscure. Therefore, the present study was undertaken to address this issue. Four groups of male Wistar rats (10 rats each) were used; control, Al₂O₃NPs treated, ZnONPs treated and Co-treated groups. Rats were orally administered their respective treatment daily for 75 days. The effects of each nanoparticle alone or in combination were assessed at different levels including; hepatic and renal function, structure, and redox status, nuclear DNA fragmentation, hepatic expression of mitochondrial transcription factor A (mtTFA) gene and peroxisome proliferator-activated receptor gamma-coactivator 1α (PGC-1α), systemic inflammation, and hematologic parameters. The results confirmed the hepatorenal toxicities of each nanoparticle used at the level of all parameters with suppression of the hepatic expression of mtTFA and PGC-1α. The co-exposure to both nanoparticles results in synergistic effects. From these results, we can conclude that co-exposure to aluminum oxide nanoparticles and zinc oxide nanoparticles results in more pronounced hepatorenal toxicities and systemic inflammation.

Keywords: ACP, acid phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; AlP, alkaline phosphatase; Aluminum oxide nanoparticles; CAT, catalase; Cytokines and p53; DNA fragmentation; GGT, gamma-glutamyl transferase; GPX, glutathione peroxidase; GSH, reduced glutathione; GST, glutathione S-transferase; Gene expression; LDH, lactate dehydrogenase; Oxidative stress; PGC-1α, peroxisome proliferator activator receptor gamma-coactivator 1α; ROS, reactive oxygen species; SOD, superoxide dismutase; TBARS, thiobarbituric acid-reactive substances; Zinc oxide nanoparticles; mtTFA, mitochondrial transcription factor A.