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

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

Mokhtar Ibrahim Yousef  1 , Thulfiqar Fawwaz Mutar  1 , Maher Abd El-Nabi Kamel  2
Affiliations

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

Mokhtar Ibrahim Yousef et al. Toxicol Rep. .

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.

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Conflict of interest statement

The authors report no conflict of interest.

The authors declare that there are no conflicts of interest and agreed to submit this article to the journal “Toxicology Reports”

Figures

None
Graphical abstract
Fig. 1
Fig. 1
DLS size distribution of hydrodynamic size of Aluminum oxide nanoparticles (A) and Zinc oxide nanoparticles (B).
Fig. 2
Fig. 2
Stained agarose gel of genomic DNA of liver (A) and kidney(B) demonstrated apoptotic and necrotic cell deaths induced by nanoparticles. Lanes 1 and 2: Control, lanes 3 and 4: Aluminum oxide nanoparticles treated rats, lanes 5 and 6: Zinc oxide nanoparticles treated rats, lanes 7and 8: Combination of aluminum oxide and zinc oxide nanoparticles treated rats.
Fig. 3
Fig. 3
Light micrographs of liver sections: Control group (A&B) showingnormal hepatic architecture and hepatic sinusoids are seen lined by endothelial cells and a Kupffer cell is seen. Aluminum oxide nanoparticles group(C &D) showing degenerative hydropicchanges and cellular infiltration in numerous hepatocytes, piecemeal necrosis, lyticnecrosis, congestion of sinusoidal blood vessels. Zinc oxide nanoparticles group (E&F) showing distended and hemorrhage in the portal veinlymphocytes aggregation, degenerated hepatocytes with pyknotic nuclei, hepatocyte vacuolization and cellular infiltration. Combination group (G&H) showing disturbed hepatic architecture in most of the lobule. Many of hepatocytes are vacuolated. While other are apoptotic, shrunken with pyknotic nuclei. Inflammatory cellular infiltration is evident in periportal areas and around the central veins. Widely dilated hepatic blood sinusoids are observed.(H & E stain. Mic.Mag. × 100 and ×400).
Fig. 4
Fig. 4
Light micrographs of kidneysections: Control group (A&B) showing normal renal corpuscles with normal glomeruli and normal Bowman's space. The distal tubules appeared having wider lumina lined by cuboidal cells with less acidophilic cytoplasm and rounded nuclei. Aluminum oxide nanoparticles group(C&D) revealed renal damages appeared as hypertrophy and degeneration of epithelia renal tubules with distinct of mononuclear cells infiltration. Zinc oxide nanoparticles group(E &F)degeneration of the tubules in the form of cytoplasmic vacuolation and distorted the renal corpuscles.Also some vascular glomeruli were apparently enlarged, tightly filling the Bowman’s capsule with absence of the capsular spaces was observed.Combination group(G&H) revealed several histopathological changes such as shrinkage of capillaries in the glomerulus with the capsular space and slightly degeneration in the epithelial cells of both proximal and distal tubules with pyknotic nuclei.(H & E stain. Mic.Mag. × 100 and ×400).
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