Colistin-induced pulmonary toxicity involves the activation of NOX4/TGF-β/mtROS pathway and the inhibition of Akt/mTOR pathway

Dai, Chongshan; Li, Meng; Sun, Tun; Zhang, Yuan; Wang, Yan; Shen, Zhangqi; Velkov, Tony; Tang, Shusheng; Shen, Jianzhong

doi:10.1016/j.fct.2022.112966

Cited by 8 publications

(8 citation statements)

References 51 publications

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“…To measure the cell apoptosis rates, an Annexin V-FITC/PI Apoptosis Detection Kit (Vazyme Biotech Co., Ltd., Nanjing, China) was employed, and the protocols were in accordance with our previous study [ 25 ]. HepG2 cells were treated with CHE at 2.5, 5, and 10 μM for 24 h, cell apoptotic rates were measured.…”

Section: Methodsmentioning

confidence: 99%

Chelerythrine-Induced Apoptotic Cell Death in HepG2 Cells Involves the Inhibition of Akt Pathway and the Activation of Oxidative Stress and Mitochondrial Apoptotic Pathway

et al. 2022

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Chelerythrine (CHE) is a majorly harmful isoquinoline alkaloid ingredient in Chelidonium majus that could trigger potential hepatotoxicity, but the pivotal molecular mechanisms remain largely unknown. In the present study, CHE-induced cytotoxicity and the underlying toxic mechanisms were investigated using human HepG2 cells in vitro. Data showed that CHE treatment (at 1.25–10 μM)-induced cytotoxicity in HepG2 cells is dose-dependent. CHE treatment increased the production of ROS and induced oxidative stress in HepG2 cells. Additionally, CHE treatment triggered the loss of mitochondrial membrane potential, decreased the expression of mitochondrial complexes, upregulated the expression of Bax, CytC, and cleaved-PARP1 proteins and the activities of caspase-9 and caspase-3, and downregulated the expression of Bcl-XL, and HO-1 proteins, finally resulting in cell apoptosis. N-acetylcysteine supplementation significantly inhibited CHE-induced ROS production and apoptosis. Furthermore, CHE treatment significantly downregulated the expression of phosphorylation (p)-Akt (Ser473), p-mTOR (Ser2448), and p-AMPK (Thr172) proteins in HepG2 cells. Pharmacology inhibition of Akt promoted CHE-induced the downregulation of HO-1 protein, caspase activation, and apoptosis. In conclusion, CHE-induced cytotoxicity may involve the inhibition of Akt pathway and the activation of oxidative stress-mediated mitochondrial apoptotic pathway in HepG2 cells. This study sheds new insights into understanding the toxic mechanisms and health risks of CHE.

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Section: Methodsmentioning

confidence: 99%

Chelerythrine-Induced Apoptotic Cell Death in HepG2 Cells Involves the Inhibition of Akt Pathway and the Activation of Oxidative Stress and Mitochondrial Apoptotic Pathway

et al. 2022

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“…Inhibition of NOX expression can effectively mitigate ROS production, thereby reducing oxidative stress and cell apoptosis. 55,56 In summary, as shown in Figure 2, thymol exhibits potent antioxidant properties by scavenging intracellular ROS, upregulating the activities of antioxidant enzymes, inhibiting NOX activities, and activating Nrf2 and AKT signaling pathways.…”

Section: •−mentioning

confidence: 99%

Thymol as a Potential Neuroprotective Agent: Mechanisms, Efficacy, and Future Prospects

Peng,

Zhang,

Sharma

et al. 2024

J. Agric. Food Chem.

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Neurodegenerative diseases pose a growing global health challenge, with limited effective therapeutic options. Mitochondrial dysfunction, oxidative stress, neuroinflammation, apoptosis, and autophagy are common underlying mechanisms in these diseases. Thymol is a phenolic monoterpene compound that has gained attention for its diverse biological properties, including antioxidant, anti-inflammatory, and immunomodulatory activities. Thymol supplementation could provide potential neuroprotection and improve cognitive deficits, depressant-like effects, learning, and memory impairments in rodents. Mechanistic investigations reveal that the neuroprotective effects of thymol involve the improvement of oxidative stress, mitochondrial dysfunction, and inflammatory response. Several signaling pathways, including mitochondrial apoptotic, NF-κB, AKT, Nrf2, and CREB/BDNF pathways are also involved. In this review, the neuroprotective effects of thymol, the potential molecular mechanisms, safety, applications, and current challenges toward development as a neuroprotective agent were summarized and discussed. We hope that this review provides valuable insights for the further development of this promising natural product as a promising neuroprotective agent.

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“…NOX4 is the main productor of endogenous ROS production [ 99 , 100 ]. Our recent study found that inhibiting NOX4 expression might considerably reduce colistin-induced nephrotoxicity and lung damage [ 101 , 102 ]. Curcumin treatment also dramatically alleviated oxidative stress damage in seminal vesicles by regulation of NOX1, NOX2, and NOX4 expressions [ 103 ].…”

Section: Curcumin’s Protective Role In Preventing Afb1-induced Toxici...mentioning

confidence: 99%

“…Apoptosis is a type of programed cell death [ 141 ]. Apoptosis could be triggered by multiple exogenous stimuli, including bio-toxins, drugs, heavy metals, ultraviolet radiation, and pathogenic microorganisms [ 102 , 142 ]. It is generally known that in mammalian cells, mitochondrial malfunction causes the activation of the mitochondrial apoptotic pathway, which in turn causes caspase-dependent apoptosis [ 137 ].…”

Section: Curcumin’s Protective Role In Preventing Afb1-induced Toxici...mentioning

confidence: 99%

Aflatoxin B1 Toxicity and Protective Effects of Curcumin: Molecular Mechanisms and Clinical Implications

et al. 2022

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One of the most significant classes of mycotoxins, aflatoxins (AFTs), can cause a variety of detrimental outcomes, including cancer, hepatitis, aberrant mutations, and reproductive issues. Among the 21 identified AFTs, aflatoxin B1 (AFB1) is the most harmful to humans and animals. The mechanisms of AFB1-induced toxicity are connected to the generation of excess reactive oxygen species (ROS), upregulation of CYP450 activities, oxidative stress, lipid peroxidation, apoptosis, mitochondrial dysfunction, autophagy, necrosis, and inflammatory response. Several signaling pathways, including p53, PI3K/Akt/mTOR, Nrf2/ARE, NF-κB, NLRP3, MAPKs, and Wnt/β-catenin have been shown to contribute to AFB1-mediated toxic effects in mammalian cells. Curcumin, a natural product with multiple therapeutic activities (e.g., anti-inflammatory, antioxidant, anticancer, and immunoregulation activities), could revise AFB1-induced harmful effects by targeting these pathways. Therefore, the potential therapeutic use of curcumin against AFB1-related side effects and the underlying molecular mechanisms are summarized. This review, in our opinion, advances significant knowledge, sparks larger discussions, and drives additional improvements in the hazardous examination of AFTs and detoxifying the application of curcumin.

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Colistin-induced pulmonary toxicity involves the activation of NOX4/TGF-β/mtROS pathway and the inhibition of Akt/mTOR pathway

Cited by 8 publications

References 51 publications

Chelerythrine-Induced Apoptotic Cell Death in HepG2 Cells Involves the Inhibition of Akt Pathway and the Activation of Oxidative Stress and Mitochondrial Apoptotic Pathway

Chelerythrine-Induced Apoptotic Cell Death in HepG2 Cells Involves the Inhibition of Akt Pathway and the Activation of Oxidative Stress and Mitochondrial Apoptotic Pathway

Thymol as a Potential Neuroprotective Agent: Mechanisms, Efficacy, and Future Prospects

Aflatoxin B1 Toxicity and Protective Effects of Curcumin: Molecular Mechanisms and Clinical Implications

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