Akademik Veri Yönetim Sistemi
14th International Symposium on Pharmaceutical Sciences (ISOPS), Ankara, Türkiye, 25 - 28 Haziran 2024, ss.308
Introduction: As a multifunctional
organ, the liver is highly vulnerable to drug-induced liver injury (DILI) due
to its high metabolic rate and biotransformation capacity, which make it
susceptible to both metabolism-related and drug-induced damage (1). One of the
causes of hepatotoxicity is oxidative stress, which occurs when radicals formed
during metabolism overwhelm the antioxidant defense capacity (2). The objective
of this study was to examine the ameliorative effects of sitagliptin, which is
endowed with anti-inflammatory, antioxidant, and anti-apoptotic properties,
against damage induced by tert-Butyl hydroperoxide (TBHP) in HepG2
cells.
Materials and Methods: HepG2 human
hepatocellular liver carcinoma cells were acquired from the ATCC (HB-8065™).
The cell viabilities were determined using MTT and neutral red uptake (NRU)
assays (3). The experiments were conducted by seeding 1x104 cells
per well in 96-well microplates. Sitagliptin and TBHP at eight concentrations (1,
5, 10, 50, 100, 250, 500, and 1000 μM) were applied for 24 hours. Based on the
obtained results, one concentration of TBHP that significantly altered cell
viability and three concentrations of sitagliptin that did not significantly
affect cell viability were selected. The selected concentrations of sitagliptin
and TBHP were administered together, and their effects on cell viability were
compared to the application of TBHP alone.
Results: According to
the results of MTT and NRU assays, sitagliptin reduced cell viability at
maximum levels of 20-25% in the tested concentrations. To assess sitagliptin's
protective potential, concentrations of 10, 15, 50, and 100 μM were chosen, as
these concentrations exhibited no cytotoxic effects. TBHP, on the other hand, inhibited
cell viability at levels of approximately 80% in the highest three
concentrations. The chosen concentration of TBHP was 250 μM. In combined
exposure, no effect of sitagliptin on TBHP-induced cell inhibition was
observed.
Conclusions: At the selected concentrations, sitagliptin did not
alter the levels of TBHP-induced cell viability inhibition. Further
investigation into sitagliptin's potential anti-inflammatory, antioxidant, and
anti-apoptotic properties could be conducted by exploring different concentrations
and/or endpoints.
Acknowledgements
This
research did not receive any specific grant from funding agencies.