Protective effect of luteolin against oxidative stress‑mediated cell injury via enhancing antioxidant systems

Fernando,Pincha Devage Sameera Madushan; Ko,Dong Ok; Piao,Mei Jing; Kang,Kyoung Ah; Herath,Herath Mudiyanselage Udari Lakmini; Hyun,Jin Won

doi:10.3892/mmr.2024.13244

Protective effect of luteolin against oxidative stress‑mediated cell injury via enhancing antioxidant systems

Authors:
- Pincha Devage Sameera Madushan Fernando
- Dong Ok Ko
- Mei Jing Piao
- Kyoung Ah Kang
- Herath Mudiyanselage Udari Lakmini Herath
- Jin Won Hyun
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Affiliations: Department of Biochemistry, College of Medicine, and Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea
Published online on: May 15, 2024 https://doi.org/10.3892/mmr.2024.13244
Article Number: 121
Copyright: © Fernando et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Physiological stress such as excessive reactive oxygen species (ROS) production may contribute normal fibroblasts activation into cancer‑associated fibroblasts, which serve a crucial role in certain types of cancer such as pancreatic, breast, liver and lung cancer. The present study aimed to examine the cytoprotective effects of luteolin (3',4',5,7‑tetrahydroxyflavone) against hydrogen peroxide (H₂O₂)‑generated oxidative stress in lung fibroblasts. To examine the effects of luteolin against H₂O₂‑induced damages, cell viability, sub‑G₁ cell population, nuclear staining with Hoechst 33342, lipid peroxidation and comet assays were performed. To evaluate the effects of luteolin on the protein expression level of apoptosis, western blot assay was performed. To assess the antioxidant effects of luteolin, detection of ROS using H₂DCFDA staining, O₂‑ and ·OH using electron spin resonance spectrometer and antioxidant enzyme activity was performed. In a cell‑free chemical system, luteolin scavenges superoxide anion and hydroxyl radical generated by xanthine/xanthine oxidase and the Fenton reaction (FeSO₄/H₂O₂). Furthermore, Chinese hamster lung fibroblasts (V79‑4) treated with H₂O₂ showed a significant increase in cellular ROS. Intracellular ROS levels and damage to cellular components such as lipids and DNA in H₂O₂‑treated cells were significantly decreased by luteolin pretreatment. Luteolin increased cell viability, which was impaired following H₂O₂ treatment and prevented H₂O₂‑mediated apoptosis. Luteolin suppressed active caspase‑9 and caspase‑3 levels while increasing Bcl‑2 expression and decreasing Bax protein levels. Additionally, luteolin restored levels of glutathione that was reduced in response to H₂O₂. Moreover, luteolin enhanced the activity and protein expressions of superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase‑1. Overall, these results indicated that luteolin inhibits H₂O₂‑mediated cellular damage by upregulating antioxidant enzymes.

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