Erzhi Pill® Repairs Experimental Liver Injury via TSC/mTOR Signaling Pathway Inhibiting Excessive Apoptosis

Zhou, Baosen; Zhao, Hai-Mei; Lu, Xiu-Yun; Wang, Xin; Zou, Yong; Xu, Rong; Yue, Hai-Yang; Liu, Yi; Zuo, Zheng-Yun; Liu, Duan-Yong

doi:10.1155/2017/5653643

Cited by 8 publications

(11 citation statements)

References 79 publications

(76 reference statements)

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“…The characteristics of liver injury recurred in the rats with 2-AAF-induced liver injury without treatment, which included decreased concentration of albumin, and elevated AST and ALT, and typical pathological changes. The changes in the Model group were consistent with those in our previous studies ( Zhou et al, 2017 ). We showed that 2-AAF/PH-induced hepatic injury was successfully prepared in the present study.…”

Section: Discussionsupporting

confidence: 91%

“…However, it is unclear whether EZP inhibits the PI3K/AKT/Raptor/Rictor signaling pathway to treat liver diseases. In our previous study, we had demonstrated that EZP relieved liver injury induced by 2-acetylaminofluorene/partial hepatectomy (2-AAF/PH), and decreased aminotransferase levels to protect liver tissues by deactivating the TSC/mTOR signaling pathway ( Zhou et al, 2017 ). Nevertheless, as the upstream signal proteins of the TSC/mTOR signaling pathway, the change in the PI3K/AKT signaling pathway and cell cycle were not observed.…”

Section: Introductionmentioning

confidence: 99%

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Erzhi Pill® Protected Experimental Liver Injury Against Apoptosis via the PI3K/Akt/Raptor/Rictor Pathway

Zhao

Zhang

et al. 2018

Front. Pharmacol.

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Erzhi Pill (EZP) is one of the basic prescriptions for treating liver diseases in traditional Chinese medicine. However, its mechanism of action is still undefined. The PI3K/AKT/Raptor/Rictor signaling pathway is closely related to apoptosis and plays a significant role in the pathogenesis of liver disease. To define the mechanism of the hepatoprotective effect of EZP in the treatment of liver disease, hepatic injury induced by 2-acetylaminofluorene/partial hepatectomy was treated by EZP for 14 days. The therapeutic effect of EZP was confirmed by the decreased production of aspartate aminotransferase and alanine aminotransferase, recovery of pathological liver injury, followed by inhibition of pro-inflammatory cytokines and transforming growth factor-β1. Bromodeoxyuridine assay and TUNEL staining indicated that apoptosis was suppressed and the numbers of cells in S phase and G0/G1phase were decreased. The crucial proteins in the PI3K/AKT/Raptor/Rictor signaling pathway were deactivated in rats with experimental liver injury treated by EZP. These results indicated that the hepatoprotective effect of EZP via inhibition of hepatocyte apoptosis was closely related to repression of the PI3K/Akt/Raptor/Rictor signaling pathway.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Erzhi Pill® Protected Experimental Liver Injury Against Apoptosis via the PI3K/Akt/Raptor/Rictor Pathway

Zhao

Zhang

et al. 2018

Front. Pharmacol.

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“…Apoptosis, also known as programmed cell death, is a critical mechanism for maintaining cell stability; however, too much can damage the body [25]. Usually, apoptosis, an early event in kidney I/R injury, interacts with the subsequent inflammation and kidney injury [26].…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Protects against Ischemia and Reperfusion-Induced Kidney Injury in Rats

Bao

Dai

2020

Mediators of Inflammation

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Acute kidney injury (AKI), a clinical syndrome, is a sudden onset of kidney failure that severely affects the kidney tubules. One potential treatment is dexmedetomidine (DEX), a highly selective α2-adrenoreceptor agonist that is used as an anesthetic adjuvant. It also has anti-inflammatory, neuroprotective, and sympatholytic qualities. The aim of this study was to establish whether DEX also offers protection against ischemia and reperfusion- (I/R-) induced AKI in rats. An intraperitoneal injection of DEX (25 μg/kg) was administered 30 min prior to the induction of I/R. The results indicate that in the I/R rats, DEX played a protective role by reducing the damage to the tubules and maintaining renal function. Furthermore, in response to I/R, the DEX treatment reduced the mRNA expression of TNF-α, IL-1β, IL-6, and MCP-1 in the kidney tissues and the serum levels of TNF-α, IL-1β, IL-6, and MCP-1. DEX also reduced the levels of oxidative stress and apoptosis in the tubular cells. These results indicate that in response to I/R kidney injury, DEX plays a protective role by inhibiting inflammation and tubular cell apoptosis, reducing the production of reactive oxygen species, and promoting renal function.

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“…However, the excessive apoptosis has adverse effects on the body. According to reports, apoptosis induces damage to a variety of tissues, including those of the kidney [ 48 , 49 ]. In the present study, TUNEL results showed that apoptosis was involved in the process of kidney injury induced by acute stress.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Ameliorates Acute Stress‐Induced Kidney Injury by Attenuating Oxidative Stress and Apoptosis through Inhibition of the ROS/JNK Signaling Pathway

Chen

Feng

et al. 2018

Oxidative Medicine and Cellular Longevity

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Acute stress induces tissue damage through excessive oxidative stress. Dexmedetomidine (DEX) reportedly has an antioxidant effect. However, protective roles and related potential molecular mechanisms of DEX against kidney injury induced by acute stress are unknown. Herein, rats were forced to swim 15 min followed by restraint stress for 3 h with/without DEX (30 μg/kg). Successful model establishment was validated by an open-field test. Assessment of renal function (creatinine, urea nitrogen), histopathology, oxidative stress (malondialdehyde, glutathione, and superoxide dismutase), and apoptosis (transferase-mediated dUTP nick end labeling) was performed. Localization of apoptosis was determined by immunohistochemistry of cleaved caspase 3 protein. In addition, key proteins of the death receptor-mediated pathway, mitochondrial pathway, endoplasmic reticulum stress (ERS) pathway, and ROS/JNK signaling pathway were measured by Western blot. We found that DEX significantly improved renal dysfunction, ameliorated kidney injury, reduced oxidative stress, and alleviated apoptosis. DEX also inhibited the release of norepinephrine (NE), decreased the production of reactive oxygen species (ROS), and inhibited JNK phosphorylation. Additionally, DEX downregulated the expression of Bax, cytochrome C, cleaved caspase 9, and cleaved caspase 3 proteins in mitochondria-dependent pathways. In summary, DEX protects against acute stress-induced kidney injury in rats by reducing oxidative stress and apoptosis via inhibition of the ROS/JNK pathway.

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Erzhi Pill® Repairs Experimental Liver Injury via TSC/mTOR Signaling Pathway Inhibiting Excessive Apoptosis

Cited by 8 publications

References 79 publications

Erzhi Pill® Protected Experimental Liver Injury Against Apoptosis via the PI3K/Akt/Raptor/Rictor Pathway

Erzhi Pill® Protected Experimental Liver Injury Against Apoptosis via the PI3K/Akt/Raptor/Rictor Pathway

Dexmedetomidine Protects against Ischemia and Reperfusion-Induced Kidney Injury in Rats

Dexmedetomidine Ameliorates Acute Stress‐Induced Kidney Injury by Attenuating Oxidative Stress and Apoptosis through Inhibition of the ROS/JNK Signaling Pathway

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