N-acetyl cysteine treatment mitigates biomarkers of oxidative stress in different tissues of bile duct ligated rats

Ommati, Mohammad Mehdi; Amjadinia, Ali; Mousavi, Khadijeh; Azarpira, Negar; Jamshidzadeh, Akram; Heidari, Reza

doi:10.1080/10253890.2020.1777970

Cited by 37 publications

(30 citation statements)

References 88 publications

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“…This finding places mitochondria-generated ROS as an early event in hypoxia/CoCl 2 -induced mitophagy. For this reason, antioxidants such as NAC improve mitochondrial function by counteracting ROS-induced mitochondrial damage in several models of human pathophysiological conditions [ 44 , 45 ]. By protecting against mitochondria-generated ROS, we demonstrate in the current study that antioxidants also mitigate the extent of mitochondrial stress, mitophagy, and restored mitochondrial bioenergetics.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitination and receptor-mediated mitophagy converge to eliminate oxidation-damaged mitochondria during hypoxia

et al. 2021

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The contribution of the Ubiquitin-Proteasome System (UPS) to mitophagy has been largely attributed to the E3 ubiquitin ligase Parkin. Here we show that in response to the oxidative stress associated with hypoxia or the hypoxia mimic CoCl 2 , the damaged and fragmented mitochondria are removed by Parkin-independent mitophagy. Mitochondria isolated from hypoxia or CoCl 2 -treated cells exhibited extensive ubiquitination, predominantly Lysine 48-linked and involves the degradation of key mitochondrial proteins such as the mitofusins MFN1/2, or the import channel component TOM20. Reflecting the critical role of mitochondrial protein degradation, proteasome inhibition blocked CoCl 2 -induced mitophagy. The five conserved ubiquitin-binding autophagy receptors (p62, NDP52, Optineurin, NBR1, TAX1BP1) were dispensable for the ensuing mitophagy, suggesting that the mitophagy step itself was independent of ubiquitination. Instead, the expression of two ubiquitin-independent mitophagy receptor proteins BNIP3 and NIX was induced by hypoxia or CoCl 2 -treatment followed by their recruitment to the oxidation-damaged mitochondria. By employing BNIP3/NIX double knockout and DRP1-null cell lines, we confirmed that mitochondrial clearance relies on DRP1-dependent mitochondrial fragmentation and BNIP3/NIX-mediated mitophagy. General antioxidants such as N -Acetyl Cysteine (NAC) or the mitochondria-specific Mitoquinone prevented HIF-1α stabilization, ameliorated hypoxia-related mitochondrial oxidative stress, and suppressed mitophagy. We conclude that the UPS and receptor-mediated autophagy converge to eliminate oxidation-damaged mitochondria.

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Section: Discussionmentioning

confidence: 99%

Ubiquitination and receptor-mediated mitophagy converge to eliminate oxidation-damaged mitochondria during hypoxia

et al. 2021

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“…Multiple studies have shown that MHC induced a systemic increase of oxidative stress. Specially, enhanced pro-oxidative biomarkers and diminished antioxidant mechanisms have been reported in brain from MHC rats (Ommati et al, 2020). In blood vessels, superoxide anions can modulate the role of NO, diminishing its bioavailability.…”

Section: Discussionmentioning

confidence: 98%

Hepatic Encephalopathy-Associated Cerebral Vasculopathy in Acute-on-Chronic Liver Failure: Alterations on Endothelial Factor Release and Influence on Cerebrovascular Function

et al. 2020

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The acute-on-chronic liver failure (ACLF) is a syndrome characterized by liver decompensation, hepatic encephalopathy (HE) and high mortality. We aimed to determine the mechanisms implicated in the development of HE-associated cerebral vasculopathy in a microsurgical liver cholestasis (MHC) model of ACLF. Microsurgical liver cholestasis was induced by ligating and extracting the common bile duct and four bile ducts. Sham-operated and MHC rats were maintained for eight postoperative weeks Bradykinin-induced vasodilation was greater in middle cerebral arteries from MHC rats. Both Nω-Nitro-L-arginine methyl ester and indomethacin diminished bradykinin-induced vasodilation largely in arteries from MHC rats. Nitrite and prostaglandin (PG) F1α releases were increased, whereas thromboxane (TX) B2 was not modified in arteries from MHC. Expressions of endothelial nitric oxide synthase (eNOS), inducible NOS, and cyclooxygenase (COX) 2 were augmented, and neuronal NOS (nNOS), COX-1, PGI2 synthase, and TXA2S were unmodified. Phosphorylation was augmented for eNOS and unmodified for nNOS. Altogether, these endothelial alterations might collaborate to increase brain blood flow in HE.

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“…We think that thiol-containing drugs or reinforcing agents with antioxidant properties can be used to prevent the side effects of MTX. Glutathione and N-acetyl cysteine are frequently preferred in many diseases due to their antioxidant and hydrophilic properties (31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Histological changes in methotrexate hepatotoxicity after boron application and evaluation of serum thiol-disulfide balance

Neşelioğlu

Akcan²,

Nakkas³

et al. 2021

Journal of Health Sciences and Medicine

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Aim: Methotrexate, a folic acid antagonist is a chemotherapeutic drug used in the treatment of various inflammatory diseases as well as some cancer types. The purpose of this study; it is the study of the effects of boric acid against the hepatotoxic side effects of methotrexate. Material and Method: Male Wistar albino rats were divided into five groups and each group consisted of six animals. The rats in group 1 were used as a control group. Methotrexate was administered to the rats in group 2 and boric acid to the rats in group 3. While the rats in group 4 were given first methotrexate and then boric acid, the rats in group 5 were administered boric acid first and then methotrexate. Results: Light microscopic examination revealed sinusoidal dilatation, hepatocyte degeneration, vascular congestionthrombosis, and inflammatory infiltration in the livers of rats treated with methotrexate. It was observed that the protective effect of boric acid was more effective than its treatment. In the groups given methotrexate, the level of oxidative stressrelated parameters such as lipid hydroperoxide, MPO and disulfide increased (p<0.05 for all parameters), whereas the level of antioxidant parameters such as native thiol, total thiol and catalase decreased (p<0.05 for all parameters). Conclusion:In this study, the protective effect of boric acid was found to be higher than the therapeutic effect in liver damage caused by methotrexate. Oxidative hepatotoxicity resulting from methotrexate application disrupted the thiol disulfide balance and caused a shift to the oxidation side.

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N-acetyl cysteine treatment mitigates biomarkers of oxidative stress in different tissues of bile duct ligated rats

Cited by 37 publications

References 88 publications

Ubiquitination and receptor-mediated mitophagy converge to eliminate oxidation-damaged mitochondria during hypoxia

Ubiquitination and receptor-mediated mitophagy converge to eliminate oxidation-damaged mitochondria during hypoxia

Hepatic Encephalopathy-Associated Cerebral Vasculopathy in Acute-on-Chronic Liver Failure: Alterations on Endothelial Factor Release and Influence on Cerebrovascular Function

Histological changes in methotrexate hepatotoxicity after boron application and evaluation of serum thiol-disulfide balance

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