Antituberculosis Drugs (Rifampicin and Isoniazid) Induce Liver Injury by Regulating NLRP3 Inflammasomes
Patients being treated for pulmonary tuberculosis often suffer liver injury due to the effects of anti-TB drugs, and the underlying mechanisms for those injuries need to be clarified. In this study, rats and hepatic cells were administrated isoniazid (INH) and rifampin (RIF) and then treated with NL...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2021/8086253 |
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| author | Qiang Su Wei Kuang Weiyi Hao Jing Liang Liang Wu Chunmei Tang Yali Wang Tao Liu |
| author_facet | Qiang Su Wei Kuang Weiyi Hao Jing Liang Liang Wu Chunmei Tang Yali Wang Tao Liu |
| author_sort | Qiang Su |
| collection | DOAJ |
| description | Patients being treated for pulmonary tuberculosis often suffer liver injury due to the effects of anti-TB drugs, and the underlying mechanisms for those injuries need to be clarified. In this study, rats and hepatic cells were administrated isoniazid (INH) and rifampin (RIF) and then treated with NLRP3-inflammasome inhibitors (INF39 and CP-456773) or NLRP3 siRNA. Histopathological changes that occurred in liver tissue were examined by H&E staining. Additionally, the levels IL-33, IL-18, IL-1β, NLRP3, ASC, and cleaved-caspase 1 expression in the liver tissues were also determined. NAT2 and CYP2E1 expression were identified by QRT-PCR analysis. Finally, in vitro assays were performed to examine the effects of siRNA targeting NLRP3. Treatment with the antituberculosis drugs caused significant liver injuries, induced inflammatory responses and oxidative stress (OS), activated NLRP3 inflammasomes, reduced the activity of drug-metabolizing enzymes, and altered the antioxidant defense system in rats and hepatic cells. The NLRP3 inflammasome was required for INH- and RIF-induced liver injuries that were produced by inflammatory responses, OS, the antioxidant defense system, and drug-metabolizing enzymes. This study indicated that the NLRP3 inflammasome is involved in antituberculosis drug-induced liver injuries (ATLIs) and suggests NLRP3 as a potential target for attenuating the inflammation response in ATLIs. |
| format | Article |
| id | doaj-art-3c1ad0205aa84634b1d8e5943176eec8 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
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| series | Mediators of Inflammation |
| spelling | doaj-art-3c1ad0205aa84634b1d8e5943176eec82025-02-03T06:46:16ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/80862538086253Antituberculosis Drugs (Rifampicin and Isoniazid) Induce Liver Injury by Regulating NLRP3 InflammasomesQiang Su0Wei Kuang1Weiyi Hao2Jing Liang3Liang Wu4Chunmei Tang5Yali Wang6Tao Liu7Department of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, ChinaSchool of Pharmacy, North Sichuan Medical College, Nanchong, Sichuan, ChinaDepartment of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, ChinaDepartment of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, ChinaDepartment of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, ChinaDepartment of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, ChinaDepartment of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, ChinaNanchong Key Laboratory of Individualized Drug Therapy, Nanchong, Sichuan, ChinaPatients being treated for pulmonary tuberculosis often suffer liver injury due to the effects of anti-TB drugs, and the underlying mechanisms for those injuries need to be clarified. In this study, rats and hepatic cells were administrated isoniazid (INH) and rifampin (RIF) and then treated with NLRP3-inflammasome inhibitors (INF39 and CP-456773) or NLRP3 siRNA. Histopathological changes that occurred in liver tissue were examined by H&E staining. Additionally, the levels IL-33, IL-18, IL-1β, NLRP3, ASC, and cleaved-caspase 1 expression in the liver tissues were also determined. NAT2 and CYP2E1 expression were identified by QRT-PCR analysis. Finally, in vitro assays were performed to examine the effects of siRNA targeting NLRP3. Treatment with the antituberculosis drugs caused significant liver injuries, induced inflammatory responses and oxidative stress (OS), activated NLRP3 inflammasomes, reduced the activity of drug-metabolizing enzymes, and altered the antioxidant defense system in rats and hepatic cells. The NLRP3 inflammasome was required for INH- and RIF-induced liver injuries that were produced by inflammatory responses, OS, the antioxidant defense system, and drug-metabolizing enzymes. This study indicated that the NLRP3 inflammasome is involved in antituberculosis drug-induced liver injuries (ATLIs) and suggests NLRP3 as a potential target for attenuating the inflammation response in ATLIs.http://dx.doi.org/10.1155/2021/8086253 |
| spellingShingle | Qiang Su Wei Kuang Weiyi Hao Jing Liang Liang Wu Chunmei Tang Yali Wang Tao Liu Antituberculosis Drugs (Rifampicin and Isoniazid) Induce Liver Injury by Regulating NLRP3 Inflammasomes Mediators of Inflammation |
| title | Antituberculosis Drugs (Rifampicin and Isoniazid) Induce Liver Injury by Regulating NLRP3 Inflammasomes |
| title_full | Antituberculosis Drugs (Rifampicin and Isoniazid) Induce Liver Injury by Regulating NLRP3 Inflammasomes |
| title_fullStr | Antituberculosis Drugs (Rifampicin and Isoniazid) Induce Liver Injury by Regulating NLRP3 Inflammasomes |
| title_full_unstemmed | Antituberculosis Drugs (Rifampicin and Isoniazid) Induce Liver Injury by Regulating NLRP3 Inflammasomes |
| title_short | Antituberculosis Drugs (Rifampicin and Isoniazid) Induce Liver Injury by Regulating NLRP3 Inflammasomes |
| title_sort | antituberculosis drugs rifampicin and isoniazid induce liver injury by regulating nlrp3 inflammasomes |
| url | http://dx.doi.org/10.1155/2021/8086253 |
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