Betulinic acid attenuates T-2 toxin-induced cytotoxicity in porcine kidney cells by blocking oxidative stress and endoplasmic reticulum stress
Copyright © 2021 Elsevier Inc. All rights reserved..
T-2 toxin is highly cytotoxic to animals, which causes damage to animal health and great economic losses to agriculture and livestock production. Betulinic acid (BA), a naturally occurring pentacyclic lupane-type triterpenoid, has various biological and medicinal activities in vivo and in vitro. The objective of the present study was to investigate the toxic effects of T-2 toxin and the reversal effect of BA on porcine kidney (PK-15) cells. We evaluated T-2 toxin-induced apoptotic responses via oxidative stress and endoplasmic reticulum stress pathways by assessing the repair effect of BA in PK-15 cells. The results proved that T-2 toxin (1 μM, treated for 24 h) is highly toxic to PK-15 cells. After pre-treatment with BA (0.25, 0.5, and 1 μM) for 24 h, the cell viabilities were significantly increased, and the lactate dehydrogenase (LDH) in the culture media was dramatically decreased compared to that in the T-2 toxin treatment group. BA also enhanced the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and catalase (CAT) and reduced the production of reactive oxygen species (ROS) and malondialdehyde (MDA) in cells. BA also dose-dependently increased the expression of glucose regulated protein (GRP78), reduced expression of activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), the phosphorylation of protein kinase R-like endoplasmic reticulum kinase (PERK), eukaryotic initiation factor 2α (eIF2α), and intracellular Ca2+ concentration in a dose-dependent manner. In addition, BA significantly decreased the expression of cleaved-caspase-3 and caspase-12, consequently reducing T-2 toxin-induced PK-15 cell apoptosis in a dose-dependent manner. Collectively, we suggest that BA has a protective effect on T-2 toxin-induced cytotoxicity by ameliorating oxidative stress and endoplasmic reticulum stress in PK-15 cells.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:249 |
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| Enthalten in: |
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP - 249(2021) vom: 15. Nov., Seite 109124 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Xiaowen [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.01.2022 Date Revised 07.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.cbpc.2021.109124 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM327714956 |
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| 520 | |a T-2 toxin is highly cytotoxic to animals, which causes damage to animal health and great economic losses to agriculture and livestock production. Betulinic acid (BA), a naturally occurring pentacyclic lupane-type triterpenoid, has various biological and medicinal activities in vivo and in vitro. The objective of the present study was to investigate the toxic effects of T-2 toxin and the reversal effect of BA on porcine kidney (PK-15) cells. We evaluated T-2 toxin-induced apoptotic responses via oxidative stress and endoplasmic reticulum stress pathways by assessing the repair effect of BA in PK-15 cells. The results proved that T-2 toxin (1 μM, treated for 24 h) is highly toxic to PK-15 cells. After pre-treatment with BA (0.25, 0.5, and 1 μM) for 24 h, the cell viabilities were significantly increased, and the lactate dehydrogenase (LDH) in the culture media was dramatically decreased compared to that in the T-2 toxin treatment group. BA also enhanced the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and catalase (CAT) and reduced the production of reactive oxygen species (ROS) and malondialdehyde (MDA) in cells. BA also dose-dependently increased the expression of glucose regulated protein (GRP78), reduced expression of activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), the phosphorylation of protein kinase R-like endoplasmic reticulum kinase (PERK), eukaryotic initiation factor 2α (eIF2α), and intracellular Ca2+ concentration in a dose-dependent manner. In addition, BA significantly decreased the expression of cleaved-caspase-3 and caspase-12, consequently reducing T-2 toxin-induced PK-15 cell apoptosis in a dose-dependent manner. Collectively, we suggest that BA has a protective effect on T-2 toxin-induced cytotoxicity by ameliorating oxidative stress and endoplasmic reticulum stress in PK-15 cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Betulinic acid | |
| 650 | 4 | |a Endoplasmic reticulum stress | |
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| 700 | 1 | |a Wang, Xianglin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Sha |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ji |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, XiangYan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Yuanyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Linyu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Rongfang |e verfasserin |4 aut | |
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