A combination of isoliquiritigenin with <scp><i>Artemisia argyi</i></scp> and <scp><i>Ohwia caudata</i></scp> water extracts attenuates oxidative stress, inflammation, and apoptosis by modulating Nrf2/Ho‐1 signaling pathways in <scp>SD</scp> rats with doxorubicin‐induced acute cardiotoxicity

Yuan Hsieh, Dennis jine; Islam, Md. Nazmul; Kuo, Wei‐Wen; Shibu, Marthandam Asokan; Lai, Chin‐Hu; Lin, Pi‐Yu; Lin, Shinn‐Zong; Chen, Michael Yu‐Chih; Huang, Chih‐Yang

doi:10.1002/tox.23936

Cited by 6 publications

(1 citation statement)

References 56 publications

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“…In addition, literature reports indicate that zedoary turmeric ketone reduces oxidative stress, prevents mitochondrial damage, activates the Nrf2/HO-1 signaling pathway, and alleviates Dox-induced activation of extracellular signal-regulated kinase 1/2 (Erk1/2) and c-Jun N-terminal kinase (JNK) [ 19 ]. Natural compounds have also been demonstrated to inhibit oxidative stress, mitochondrial dysfunction, and cell apoptosis by upregulating the Nrf2/HO-1 signaling pathway, hence preventing Dox-induced cardiotoxicity [ 20 , 21 ]. In the present study, we discovered that, compared with the control Dox treatment group, the NSUN2 interference Dox treatment group significantly increased oxidative stress response in the interference NSUN2 expression model, while Nrf2 and its downstream HO-1, NQO1 proteins were significantly downregulated.…”

Section: Discussionmentioning

confidence: 99%

NSUN2 relies on ALYREF to regulate Nrf2-mediated oxidative stress and alleviate Dox-induced liver injury

Huang,

Li,

Wei

et al. 2024

Biol Direct

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Background Doxorubicin (Dox) is associated with various liver injuries, limiting its clinical utility. This study investigates whether NSUN2 participates in Dox-induced liver injury and the associated molecular mechanism. Methods In vivo and in vitro liver cell injury models were constructed based on Dox therapy. The protein levels of NSUN2 and oxidative stress indicators Nrf2, HO-1, and NQO1 were evaluated by Western blot. The RNA binding potential was detected by RNA methylation immunoprecipitation (RIP). Additionally, the effect of NSUN2 on Nrf2 mRNA synthesis and localization was evaluated using an RNA fluorescence probe. Results NSUN2 was downregulated, and liver tissue suffered significant pathological damage in the Dox group. The levels of ALT and AST significantly increased. NSUN2 interference exacerbated Dox-induced liver cell damage, which was reversed by NSUN2 overexpression. RIP demonstrated that NSUN2 recognized and bound to Nrf2 mRNA. Western blot analysis showed the protein level of Nrf2 in the NSUN2-WT group was significantly higher than that of the control group, whereas there was no significant change in Nrf2 level in the mutant NSUN2 group. Luciferase analysis demonstrated that NSUN2 could recognize and activate the Nrf2 5′UTR region of LO2 cells. In addition, RIP analysis revealed that ALYREF could recognize and bind to Nrf2 mRNA and that ALYREF controls the regulatory effect of NSUN2 on Nrf2. Conclusion NSUN2 regulates Dox-induced liver cell damage by increasing Nrf2 mRNA m5C methylation to inhibit inhibiting antioxidant stress. The regulatory effect of NSUN2 on Nrf2 depends on ALYREF.

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Section: Discussionmentioning

confidence: 99%

NSUN2 relies on ALYREF to regulate Nrf2-mediated oxidative stress and alleviate Dox-induced liver injury

Huang,

Li,

Wei

et al. 2024

Biol Direct

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Ohwia caudata inhibits doxorubicin‐induced cardiotoxicity by regulating mitochondrial dynamics via the IGF‐IIR/p‐Drp1/PARP signaling pathway

Chen,

Ramesh,

Islam

et al. 2024

Biotech and App Biochem

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The most effective drug, doxorubicin (DOX), is widely used worldwide for clinical application as an anticancer drug. DOX‐induced cytotoxicity is characterized by mitochondrial dysfunction. There is no alternative treatment against DOX‐induced cardiac damage despite intensive research in the present decades. Ohwia caudata has emerged as a potential herbal remedy that prevents from DOX‐induced cytotoxicity owing to its pharmacological action of sustaining mitochondrial dynamics by attenuating oxidative stress and inducing cellular longevity. However, its underlying mechanisms are unknown. The novel treatment provided here depends on new evidence from DOX‐treated H9c2 cells, which significantly enhanced insulin‐like growth factor (IGF) II receptor (IGF‐IIR) pathways that activated calcineurin and phosphorylated dynamin‐related protein 1 (p‐Drp1) at ser616 (p‐Drp1[ser616]); cells undergo apoptosis due to these factors, which translocate to mitochondria and disrupt their function and integrity, and in terms of herbal medicine treatment, which significantly blocked these phenomena. Thus, our findings indicate that maintaining integrity of mitochondria is an essential element in lowering DOX‐induced cytotoxicity, which further emphasizes that our herbal medicine can successfully block IGF‐IIR pathways and could potentially act as an alternative mechanism in terms of cardioprotective against doxorubicin.

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Betaine ameliorates doxorubicin‐induced cardiomyopathy by inhibiting oxidative stress, inflammation, and fibrosis through the modulation of AMPK/Nrf2/TGF‐β expression

Singh,

Yadav,

Patel

et al. 2024

Environmental Toxicology

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Doxorubicin (DOX) is a broad‐spectrum antibiotic with potent anti‐cancer activity. Nevertheless, despite having effective anti‐neoplasm activity, its use has been clinically restricted due to its life‐threatening side effects, such as cardiotoxicity. It is evident that betaine has anti‐oxidant, and anti‐inflammatory activity and has several beneficial effects, such as decreasing the amyloid‐β generation, reducing obesity, improving steatosis and fibrosis, and activating AMP‐activated protein kinase (AMPK). However, whether betaine could mitigate DOX‐induced cardiomyopathy is still unexplored. Cardiomyopathy was induced in male Sprague Dawley rats using DOX (4 mg/kg dose with a cumulative dose of 20 mg/kg, i.p.). Further, betaine (200 and 400 mg/kg) was co‐treated with DOX through oral gavage for 28 days. After the completion of the study, several biochemical, oxidative stress parameters, histopathology, western blotting, and qRT‐PCR were performed. Betaine treatment significantly reduced CK‐MB, LDH, SGOT, and triglyceride levels, which are associated with cardiotoxicity. DOX‐induced increased oxidative stress was also mitigated by betaine intervention as the SOD, catalase, MDA, and nitrite levels were restored. The histopathological investigation also confirmed the cardioprotective effect of betaine against DOX‐induced cardiomyopathy as the tissue injury was reversed. Further, molecular analysis revealed that betaine suppressed the DOX‐induced increased expression of phospho‐p53, phospho‐p38 MAPK, NF‐kB p65, and PINK 1 with an upregulation of AMPK and downregulation of Nrf2 expression. Interestingly, qRT‐PCR experiments show that betaine treatment alleviates the DOX‐induced increase in inflammatory (TNF‐α, NLRP3, and IL‐6) and fibrosis (TGF‐β and Acta2) related gene expression, halting the cardiac injury. Interestingly, betaine also improves the mRNA expression of Nrf2, thus modulating the expression of antioxidant proteins and preventing oxidative damage. Here, we provide the first evidence that betaine treatment prevents DOX‐induced cardiomyopathy by inhibiting oxidative stress, inflammation, and fibrosis by regulating AMPK/Nrf2/TGF‐β expression. We believe that betaine can be utilized as a potential novel therapeutic strategy for preventing DOX‐induced cardiotoxicity.

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A combination of isoliquiritigenin with Artemisia argyi and Ohwia caudata water extracts attenuates oxidative stress, inflammation, and apoptosis by modulating Nrf2/Ho‐1 signaling pathways in SD rats with doxorubicin‐induced acute cardiotoxicity

Cited by 6 publications

References 56 publications

NSUN2 relies on ALYREF to regulate Nrf2-mediated oxidative stress and alleviate Dox-induced liver injury

NSUN2 relies on ALYREF to regulate Nrf2-mediated oxidative stress and alleviate Dox-induced liver injury

Ohwia caudata inhibits doxorubicin‐induced cardiotoxicity by regulating mitochondrial dynamics via the IGF‐IIR/p‐Drp1/PARP signaling pathway

Betaine ameliorates doxorubicin‐induced cardiomyopathy by inhibiting oxidative stress, inflammation, and fibrosis through the modulation of AMPK/Nrf2/TGF‐β expression

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