6-Paradol alleviates Diclofenac-induced acute kidney injury via autophagy enhancement-mediated by AMPK/AKT/mTOR and NLRP3 inflammasome pathways

被引：13
作者：
El-Maadawy, Walaa H. [1 ]
Hassan, Marwa [2 ]
Abdou, Rabab M. [3 ]
El-Dine, Riham S. [3 ]
Aboushousha, Tarek [4 ]
El-Tanbouly, Nebal D. [3 ]
El-Sayed, Aly M. [3 ]
机构：
[1] Theodor Bilharz Res Inst, Dept Pharmacol, Imbaba PO 30, Giza 12411, Egypt
[2] Theodor Bilharz Res Inst, Dept Immunol, Imbaba PO 30, Giza 12411, Egypt
[3] Cairo Univ, Dept Pharmacognosy, Fac Pharm, Kasr El Aini St, Cairo 11562, Egypt
[4] Theodor Bilharz Res Inst, Dept Pathol, Imbaba PO 30, Giza 12411, Egypt
来源：
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY | 2022年 / 91卷
关键词：
6-paradol; Diclofenac-induced acute kidney injury; AMPK pathway; Autophagy; AKT/mTOR; NLRP3; pathway; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; OXIDATIVE STRESS; ACTIVATION; CONSTITUENTS; INHIBITION; AXIS;
D O I：
10.1016/j.etap.2022.103817
中图分类号：
X [环境科学、安全科学];
学科分类号：
08 ; 0830 ;
摘要：
Diclofenac (DIC)-induced acute kidney injury (AKI) causes high morbidity and mortality. With the absence of satisfactory treatment, we investigated the protective effects of 6-Paradol (PDL) against DIC-induced AKI, with focus on renal autophagy and NLRP3 inflammasome pathways . PDL has anti-inflammatory, antioxidant and AMPK-activation properties. PDL was administered to DIC-challenged rats. Nephrotoxicity, oxidative stress, inflammatory, and autophagy markers and histopathological examinations were evaluated. Compared to DIC, PDL restored serum nephrotoxicity, renal oxidative stress and pro-inflammatory markers. PDL almost restored renal architecture, upregulated renal Nrf2 pathway via enhancing Nrf2 mRNA expression and HO-1 levels. PDL suppressed renal NF-kappa B mRNA expression, and NLRP3 inflammasome pathway expression. Moreover, PDL enhanced renal autophagy through upregulating LC3B, AMPK and SIRT-1, and suppressed mTOR, p-AKT mRNA expressions and phosphorylated-p62 levels. Our study confirmed that autophagy suppression mediates DICinduced AKI via AMPK/mTOR/AKT and NLRP3-inflammasome pathways. Also, PDL's nephroprotective effects could provide a promising therapeutic approach against DIC-induced AKI.
引用
收藏
页数：10
相关论文
共 45 条
[1]   Nephroprotective activity of Aframomum melegueta seeds extract against diclofenac-induced acute kidney injury: A mechanistic study [J].
Abdou, Rabab M. ;
El-Maadawy, Walaa H. ;
Hassan, Marwa ;
El-Dine, Riham S. ;
Aboushousha, Tarek ;
El-Tanbouly, Nebal D. ;
El-Sayed, Aly M. .
JOURNAL OF ETHNOPHARMACOLOGY, 2021, 273
[2]   Nephrotoxicity: Role and significance of renal biomarkers in the early detection of acute renal injury [J].
Al-Naimi, Marwa S. ;
Rasheed, Huda A. ;
Hussien, Nawar R. ;
Al-Kuraishy, Hayder M. ;
Al-Gareeb, Ali I. .
JOURNAL OF ADVANCED PHARMACEUTICAL TECHNOLOGY & RESEARCH, 2019, 10 (03) :95-99
[3]   Pyrrolidine dithiocarbamate inhibits mouse acute kidney injury induced by diclofenac by targeting oxidative damage, cytokines and NF-κB activity [J].
Borghi, Sergio M. ;
Fattori, Victor ;
Ruiz-Miyazawa, Kenji W. ;
Bertozzi, Mariana M. ;
Lourenco-Gonzalez, Yuri ;
Tatakihara, Roberto I. ;
Bussmann, Allan J. C. ;
Mazzuco, Tania L. ;
Casagrande, Rubia ;
Verri, Waldiceu A., Jr. .
LIFE SCIENCES, 2018, 208 :221-231
[4]   Ugonin U stimulates NLRP3 inflammasome activation and enhances inflammasome-mediated pathogen clearance [J].
Chen, Chun-Yu ;
Yang, Chuan-Hui ;
Tsai, Yung-Fong ;
Liaw, Chih-Chuang ;
Chang, Wen-Yi ;
Hwang, Tsong-Long .
REDOX BIOLOGY, 2017, 11 :263-274
[5]   Cadmium exposure induces rat proximal tubular cells injury via p62-dependent Nrf2 nucleus translocation mediated activation of AMPK/AKT/mTOR pathway [J].
Dong, Wenxuan ;
Liu, Gang ;
Zhang, Kanglei ;
Tan, Yun ;
Zou, Hui ;
Yuan, Yan ;
Gu, Jianhong ;
Song, Ruilong ;
Zhu, Jiaqiao ;
Liu, Zongping .
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, 2021, 214
[6]   Vinpocetine reduces diclofenac-induced acute kidney injury through inhibition of oxidative stress, apoptosis, cytokine production, and NF-κB activation in mice [J].
Fattori, Victor ;
Borghi, Sergio M. ;
Guazelli, Carla F. S. ;
Giroldo, Andressa C. ;
Crespigio, Jefferson ;
Bussmann, Allan J. C. ;
Coelho-Silva, Leticia ;
Ludwig, Natasha G. ;
Mazzuco, Tania L. ;
Casagrande, Rubia ;
Verri, Waldiceu A., Jr. .
PHARMACOLOGICAL RESEARCH, 2017, 120 :10-22
[7]  
FREIREICH EMIL J., 1966, CANCER CHEMOTHERAP REP, V50, P219
[8]   Neuroprotective Effect of 6-Paradol in Focal Cerebral Ischemia Involves the Attenuation of Neuroinflammatory Responses in Activated Microglia [J].
Gaire, Bhakta Prasad ;
Kwon, Oh Wook ;
Park, Sung Hyuk ;
Chun, Kwang-Hoon ;
Kim, Sun Yeou ;
Shin, Dong Yun ;
Choi, Ji Woong .
PLOS ONE, 2015, 10 (03)
[9]   Omeprazole attenuates cisplatin-induced kidney injury through suppression of the TLR4/NF-κB/NLRP3 signaling pathway [J].
Gao, Huan ;
Wang, Xiangfeng ;
Qu, Xiaoyu ;
Zhai, Jinghui ;
Tao, Lina ;
Zhang, Yueming ;
Song, Yanqing ;
Zhang, Wenrui .
TOXICOLOGY, 2020, 440
[10]   SIRT1 Negatively Regulates the Mammalian Target of Rapamycin [J].
Ghosh, Hiyaa Singhee ;
McBurney, Michael ;
Robbins, Paul D. .
PLOS ONE, 2010, 5 (02)
12345