Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation
Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress and p...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00479/full |
| _version_ | 1811226530115747840 |
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| author | Li Gao weifeng Wu guiling Ren haidi Li qin Yang xiaofeng Li tao Xu zeng Li baoming Wu taotao Ma cheng Huang dong Lei yan Hang lei Zhang xiongwen Lv Jun Li Xiaoming Meng |
| author_facet | Li Gao weifeng Wu guiling Ren haidi Li qin Yang xiaofeng Li tao Xu zeng Li baoming Wu taotao Ma cheng Huang dong Lei yan Hang lei Zhang xiongwen Lv Jun Li Xiaoming Meng |
| author_sort | Li Gao |
| collection | DOAJ |
| description | Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress and programmed cell death of renal tubular epithelial cells. All of which lead to higher mortality rates in patients. In this study we examined the protective effect of protocatechuic aldehyde (PA) in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy. PA is a monomer of Traditional Chinese Medicine isolated from the root of S. miltiorrhiza. Results show that PA prevented cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both mRNA and protein levels. Moreover, PA reduced renal inflammation by suppressing oxidative stress and programmed cell death in response to cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in cisplatin-induced acute kidney injury. Collectively, our data indicate that PA largely blocked cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation without compromising anti-tumor activity of cisplatin. These findings suggest that PA and its derivatives may serve as potential protective agents for cancer patients with cisplatin treatment. |
| first_indexed | 2024-04-12T09:26:40Z |
| format | Article |
| id | doaj.art-345a37246826497c8efe36827fcaec65 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T09:26:40Z |
| publishDate | 2016-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-345a37246826497c8efe36827fcaec652022-12-22T03:38:28ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122016-12-01710.3389/fphar.2016.00479224636Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammationLi Gao0weifeng Wu1guiling Ren2haidi Li3qin Yang4xiaofeng Li5tao Xu6zeng Li7baoming Wu8taotao Ma9cheng Huang10dong Lei11yan Hang12lei Zhang13xiongwen Lv14Jun Li15Xiaoming Meng16School of Pharmacy, Anhui Medical University. Anhui, ChinaSchool of Pharmacy, Anhui Medical University. Anhui, ChinaSchool of Pharmacy, Anhui Medical University. Anhui, ChinaSchool of Pharmacy, Anhui Medical University. Anhui, ChinaSchool of Pharmacy, Anhui Medical University. Anhui, ChinaSchool of Pharmacy, Anhui Medical University. Anhui, ChinaSchool of Pharmacy, Anhui Medical University. Anhui, ChinaSchool of Pharmacy, Anhui Medical University. Anhui, ChinaSchool of Pharmacy, Anhui Medical University. Anhui, ChinaSchool of Pharmacy, Anhui Medical University. Anhui, ChinaSchool of Pharmacy, Anhui Medical University. Anhui, ChinaEmory University School of MedicineSchool of Pharmacy, Anhui Medical University. Anhui, ChinaSchool of Pharmacy, Anhui Medical University. Anhui, ChinaSchool of Pharmacy, Anhui Medical University. Anhui, ChinaSchool of Pharmacy, Anhui Medical University. Anhui, ChinaSchool of Pharmacy, Anhui Medical University. Anhui, ChinaCisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress and programmed cell death of renal tubular epithelial cells. All of which lead to higher mortality rates in patients. In this study we examined the protective effect of protocatechuic aldehyde (PA) in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy. PA is a monomer of Traditional Chinese Medicine isolated from the root of S. miltiorrhiza. Results show that PA prevented cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both mRNA and protein levels. Moreover, PA reduced renal inflammation by suppressing oxidative stress and programmed cell death in response to cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in cisplatin-induced acute kidney injury. Collectively, our data indicate that PA largely blocked cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation without compromising anti-tumor activity of cisplatin. These findings suggest that PA and its derivatives may serve as potential protective agents for cancer patients with cisplatin treatment.http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00479/fullAcute Kidney InjuryInflammationOxidative StressNOX4necroptosisProtocatechuic aldehyde |
| spellingShingle | Li Gao weifeng Wu guiling Ren haidi Li qin Yang xiaofeng Li tao Xu zeng Li baoming Wu taotao Ma cheng Huang dong Lei yan Hang lei Zhang xiongwen Lv Jun Li Xiaoming Meng Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation Frontiers in Pharmacology Acute Kidney Injury Inflammation Oxidative Stress NOX4 necroptosis Protocatechuic aldehyde |
| title | Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation |
| title_full | Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation |
| title_fullStr | Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation |
| title_full_unstemmed | Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation |
| title_short | Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation |
| title_sort | protocatechuic aldehyde attenuates cisplatin induced acute kidney injury by suppressing nox mediated oxidative stress and renal inflammation |
| topic | Acute Kidney Injury Inflammation Oxidative Stress NOX4 necroptosis Protocatechuic aldehyde |
| url | http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00479/full |
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