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Updated: Aug 8, 2026
High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents HPHC
Published on: May 10, 2016
The molecular effect of 1,4,7-triazacyclononane on oxidative stress parameters in human hepatocellular carcinoma
Simphiwe Mcoyi1, Daniel G Amoako1,2, Anou M Somboro1,2
1Drug and Innovation Research Unit, Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban, South Africa.
Abstract:
Antibiotic resistance poses a great threat to human, animal and environmental health. β-Lactam antibiotics have been successful in combating bacterial infections. However, the overuse, inappropriate prescribing, unavailability of new antibiotics and regulation barriers have exacerbated bacterial resistance to these antibiotics. 1,4,7-Triazacyclononane (TACN) is a cyclic organic tridentate inhibitor with strong metal-chelating abilities that has been shown to inhibit β-lactamase enzymes and may represent an important breakthrough in the treatment of drug-resistant bacterial strains. However, its cytotoxicity in the liver is unknown. This study aimed to determine the effect of TACN on oxidative stress in HepG2 cells. The HepG2 cells were treated with 0 to 500 µM TACN for 24 hours to obtain an IC50 for use in subsequent assays. Free radicals were measured using the thiobarbituric acid reactive substance and nitric oxide synthase assays, respectively, while antioxidant levels were assessed using luminometry (glutathione [GSH] and adenosine triphosphate [ATP]) and Western blot analysis (SOD, catalase, GPx-1, HSP70 and Nrf2). Percentage survival fluctuated as TACN concentration increased with a calculated IC50 of 545 µM. A slight increase in HSP70 and Nrf2 expression indicated the presence of stress and a response against it, respectively. However, free radical production was not increased as indicated by decreased malondialdehyde levels and reactive nitrogen species. Glutathione levels increased slightly, while ATP levels were marginally altered. The results suggest that TACN does not induce oxidative stress in HepG2 cells and can be exploited as a potential inhibitor.
Insights
1,4,7-Triazacyclononane (TACN) shows potential as an antibiotic resistance treatment. Studies indicate TACN does not induce oxidative stress in liver cells, suggesting it is safe for further development against drug-resistant bacteria.
Area of Science:
- Biochemistry
- Toxicology
- Pharmacology
Background:
- Antibiotic resistance is a significant global health threat, driven by factors including overuse and lack of new drugs.
- Beta-lactam antibiotics are crucial, but resistance is increasing.
- 1,4,7-Triazacyclononane (TACN) inhibits beta-lactamase enzymes, offering a potential strategy against resistant bacteria.
Purpose of the Study:
- To investigate the potential hepatotoxicity of TACN by examining its effect on oxidative stress in HepG2 liver cells.
- To determine if TACN induces oxidative stress or if it possesses protective antioxidant properties.
Main Methods:
- HepG2 cells were exposed to varying concentrations of TACN (0-500 µM) for 24 hours to determine the IC50.
- Oxidative stress markers (malondialdehyde, reactive nitrogen species) and antioxidant levels (glutathione, ATP, SOD, catalase, GPx-1, HSP70, Nrf2) were measured.
- Assays included thiobarbituric acid reactive substance, nitric oxide synthase, luminometry, and Western blot analysis.
Main Results:
- The calculated IC50 for TACN was 545 µM, indicating moderate toxicity at high concentrations.
- TACN treatment did not increase free radical production; malondialdehyde and reactive nitrogen species levels decreased.
- Slight increases in glutathione, HSP70, and Nrf2 suggest a mild stress response without significant damage.
Conclusions:
- TACN does not appear to induce significant oxidative stress in HepG2 cells at relevant concentrations.
- TACN demonstrates potential as a safe therapeutic agent for combating antibiotic resistance.
- Further research into TACN's efficacy and safety profile is warranted for clinical applications.
