A Titanium (IV)-Dithiophenolate Complex and Its Chitosan Nanocomposite: Their Roles towards Rat Liver Injuries In Vivo and against Human Liver Cancer Cell Lines.

Nadia Z Shaban,Salah A Yehia,Samar R Saleh,Doaa Awad,Shaban Y Shaban

doi:10.3390/ijms222011219

Nadia Z Shaban, Salah A Yehia + Show 3 more

Open Access

https://doi.org/10.3390/ijms222011219

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Abstract

Titanium (IV)–dithiophenolate complex chitosan nanocomposites (DBT–CSNPs) are featured by their antibacterial activities, cytotoxicity, and capacity to bind with DNA helixes. In this study, their therapeutic effects against rat liver damage induced by carbon tetrachloride (CCl4) and their anti-proliferative activity against human liver cancer (HepG2) cell lines were determined. Results of treatment were compared with cisplatin treatment. Markers of apoptosis, oxidative stress, liver functions, and liver histopathology were determined. The results showed that DBT–CSNPs and DBT treatments abolished liver damage induced by CCl4 and improved liver architecture and functions. DNA fragmentation, Bax, and caspase-8 were reduced, but Bcl-2 and the Bcl-2/Bax ratios were increased. However, there was a non-significant change in the oxidative stress markers. DBT–CSNPs and DBT inhibited the proliferation of HepG2 cells by arresting cells in the G2/M phase and inducing cell death. DBT–CSNPs were more efficient than DBT. Low doses of DBT and DBT–CSNPs applied to healthy rats for 14 days had no adverse effect. DBT and DBT–CSNP treatment gave preferable results than the treatment with cisplatin. In conclusion, DBT–CSNPs and DBT have anti-apoptotic activities against liver injuries and have anti-neoplastic impacts. DBT–CSNPs are more efficient. Both compounds can be used in pharmacological fields.

Highlights

The liver is the largest solid organ in the body and is required for survival
The current results showed that the LD50 values of DBT and DBT–CS nanoparticles (CSNPs) were about
The current results showed that treatment of HepG2 cells with DBT and DBT–CSNPs caused a significant decrease in the population of HepG2 cells in the G0/G1 and S phases when compared with normal cells (Figure 6)

Summary

Introduction

The liver has numerous functions including the synthesis of proteins, glucose, bile, and clotting factors and the breaking down of hormones, certain drugs, and xenobiotics [1,2]. Hepatic metabolism of some drugs and toxins such as carbon tetrachloride (CCl4 ) augments the generation of free radicals and reactive oxygen species (ROS), resulting in oxidative stress (OS), hepatoxicity, and deterioration of macromolecules as proteins, lipids, carbohydrates, and nucleic acids [3,4]. Are well known for playing a dual function as both harmful and beneficial species. There is increasing evidence that “double-faced” ROS in cells act as secondary messengers in intracellular signaling cascades, which stimulate and preserve the oncogenic phenotype of cancer cells, while ROS can prompt cellular senescence and apoptosis and can function as antitumorigenic species [5,6]. CCl4 is metabolized by cytochrome P450 into the trichloromethyl radical ( CCl3 ), which is converted into trichloromethylperoxy radicals (CCl3 OO ) [5,6]

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