Organ-specific renal tissue damage manifested by single-walled carbon-nanotubes and single-walled carbon-nanotubes-silver-titania nanocomposite: Cellular toxicity at high doses

• Published in: Journal of trace elements in medicine and biology 2024-12, Vol.86, p.127569, Article 127569
• Main Authors: Obaid, Khalid Ali, Imarah, Ameer A., Khalfa, Hydar M., Sulaiman, Ghassan M., Jabir, Majid S., Mohammed, Mustafa K.A., Ahmed, Duha S., Al-Kuraishy, Hayder M., Nayef, Uday M., Mohammed, Hamdoon A., Khan, Riaz A., Jawad, Sabrean F.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Cell Line; DNA Damage - drug effects; Dose-Response Relationship, Drug; HK-2 Cells; Humans; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Male; Mice; Micronucleus Tests; Nanocomposites - chemistry; Nanotechnology; Nanotubes, Carbon - chemistry; Nanotubes, Carbon - toxicity; Organ Specificity - drug effects; Oxidative Stress - drug effects; Oxidative Stress and Renal Injury; Reactive Oxygen Species; Reactive Oxygen Species - metabolism; Silver - chemistry; SWCNTs and SWCNTs-Ag-TiO2; Titanium - chemistry; Titanium - toxicity; Vulnerable Dose
• ISSN: 0946-672X; 1878-3252; 1878-3252
• DOI: 10.1016/j.jtemb.2024.127569

Single-walled (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) can pose risks in biological systems leading to harmful effects, such as, reactive oxygen species (ROS) formation, DNA damage, mitochondrial dysfunction, and ultimately, the cell death through apoptosis. The study assessed the nephrotoxicity of the SWCNTs and SWCNTs-Ag-TiO2 nanocomposites through in vitro and in vivo experiments, assessing oxidative stress, genotoxicity, and safety for biomedical applications. In vitro, HK-2 cell lines were utilized to evaluate the effects of nanomaterials on cellular activity, apoptosis, ROS generation, and micronuclei formations. In the in vivo study, twenty male mice were divided into five groups: the first received a control injection of phosphate-buffer saline (PBS), while the second, and third groups received daily intraperitoneal injections of SWCNTs at doses of 50 mg/kg, and 100 mg/kg, respectively, for ten days. The fourth and fifth groups received the SWCNTs-Ag-TiO2 at 50 mg/kg and 100 mg/kg, respectively, for ten days in sequence. SWCNTs and SWCNTs-Ag-TiO2 significantly promoted the micronuclei formations in HK-2 cells, with rates of 48 % and 79 %, respectively, as compared to the 12.67 % of the control group. The analysis of renal tissues revealed increased levels of ROS, DNA-protein crosslinks (DPC), glutathione (GSH), malondialdehyde (MDA), creatinine, and 8-hydroxy-2′-deoxyguanosine, while the GSH levels decreased. These findings indicated renal tissue injury, and oxidative damages. The study demonstrated the cellular toxicity of these nanomaterials, highlighting the need for caution regarding their widespread use, particularly the use of carbon nanotubes and their metallic composites at higher exposure doses in occupational, environmental, or therapeutic contexts.