Naringenin mitigates cadmium-induced cell death, oxidative stress, mitochondrial dysfunction, and inflammation in KGN cells by regulating the expression of sirtuin-1

Abstract

The objective of this study was to examine the potential protective role of naringenin against the harmful effects induced by cadmium in KGN cell line. Cell viability was evaluated by cell counting kit-8 assay. Caspase-3/-9 activities were determined by caspase-3/-9 activity assay kits, respectively. Intracellular reactive oxygen species (ROS) level was detected by ROS-Glo™ H₂O₂ Assay, antioxidant capacity was determined by a total antioxidant capacity assay kit. Mitochondrial membrane potential (MMP), ATP level, and ATP synthase activity were determined by JC-1, ATP assay kit, and ATP synthase activity assay kit, respectively. The mRNA expression was determined by qRT-PCR. Cadmium reduced cell viability and increased caspase-3/-9 activities in a concentration-dependent manner. Naringenin improved cell viability and reduced caspase-3/-9 activities in cadmium-stimulated KGN cells in a concentration-dependent manner. Cadmium diminished the antioxidant capacity, increased ROS production, and induced mitochondrial dysfunction in KGN cells. These effects were ameliorated by naringenin treatment in a concentration-dependent manner. Furthermore, naringenin reduced the levels of pro-inflammatory cytokines in KGN cells exposed to cadmium. SIRT1 knockdown downregulated its expression in KGN cells and compromised the protective effects of naringenin on cell viability and caspase-3/-9 activities in cadmium-stimulated KGN cells. Naringenin prevented the reduction of MMP, ATP levels, and ATP synthase activity in cadmium-stimulated KGN cells in a concentration-dependent manner. However, these protective effects were significantly reversed by SIRT1 knockdown. In conclusion, this study suggests that naringenin protects against cadmium-induced damage by regulating oxidative stress, mitochondrial function, and inflammation in KGN cells, with SIRT1 playing a potential mediating role.

Keywords:

• Cadmium
• cell viability
• capsase-3/-9 activities
• ROS
• mitochondrial membrane potential
• ATP

Declarations

Authors’ contributions

BY and JM performed the experiments; SL and BL analyzed the data; BY and JM prepared the figures; JW designed the study and wrote the manuscript; all the authors approved the manuscript for submission.

Competing interests

The authors declare no competing interests.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All the data are available upon request from the corresponding author.

Additional information

Funding

This study was supported by 2022 Hubei Provincial Key Research and Development Program Project from Department of Hubei Province Science and Technology (2022BCE002) and 2021 Hubei Province Key Laboratory Open Fund Project for Occupational Hazard Identification and Control (OHIC2021G13).