The involvement of sirtuin 1 and heme oxygenase 1 in the hepatoprotective effects of quercetin against carbon tetrachloride-induced sub-chronic liver toxicity in rats

Kemelo, Mighty Kgalalelo; Pierzynová, Aneta; Canová, Nikolina Kutinová; Kučera, Tomáš; Farghali, Hassan

doi:10.1016/j.cbi.2017.03.014

Cited by 26 publications

(24 citation statements)

References 61 publications

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“…Apoptosis occurred in multicellular organisms, the antiapoptotic protein Bcl‐2 and proapoptotic protein Bax are important initiators localized to the mitochondria and further activate the caspase cascade . Caspase‐3 and caspase‐9 are cysteine protease that are involved in mediating cell apoptosis; once activated, they result in cell shrinkage, DNA degradation, and the formation of apoptotic bodies cascade . It has been shown that INH may expedite physiological apoptosis by decreasing the expression of Bcl‐2, elevating Bax, activating caspase‐9 and caspase‐3 in vivo and in vitro .…”

Section: Discussionmentioning

confidence: 99%

“…Quercetin (Que) is a flavonoid compound, ubiquitous in nature, with a variety of biological activities, including antioxidant, scavenging‐free radical, anti‐inflammatory, antitumor, antiapoptosis, and immunosuppressive . Mounting evidence shows that Que could have protective effects on the heart, brain, kidney, liver, and metabolic diseases by targeting the SIRT1 pathway . Besides, research on the regulation of Que on ERK also exists .…”

Section: Introductionmentioning

confidence: 99%

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Quercetin protected against isoniazide‐induced HepG2 cell apoptosis by activating the SIRT1/ERK pathway

Zhang

Tao

et al. 2019

J Biochem & Molecular Tox

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Isoniazid (INH) is one of the most commonly used antituberculosis drugs, but its clinical applications have been limited by severe hepatic toxicity. Quercetin (Que), a natural flavonoid, has been proved to have many medicinal properties. This study aimed to clarify the possible protective effects of Que against INH‐induced hepatotoxicity using HepG2 cells. Our results indicated that Que significantly increased cell viability, superoxide dismutase, and GSH levels, while decreased alanine aminotransferase/aspartate aminotransferase levels. Besides, Que significantly abrogated INH‐induced cell apoptosis by upregulating the expression levels of Bcl‐2 and decreasing the levels of Bax, cleaved caspase‐3, and cleaved caspase‐9. Furthermore, Que obviously reversed the inhibition of INH on Sirtuin 1 (SIRT1) expression and extracellular signal‐regulated kinase (ERK) phosphorylation. Next, the SIRT1 inhibitor EX527 blocked the enhancement of Que upon ERK phosphorylation. Notably, EX527 partially abolished the beneficial effects of Que. In brief, our results provided the first evidence that Que protected against INH‐induced HepG2 cells by regulating the SIRT1/ERK pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quercetin protected against isoniazide‐induced HepG2 cell apoptosis by activating the SIRT1/ERK pathway

Zhang

Tao

et al. 2019

J Biochem & Molecular Tox

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“…Quercetin, an organic flavone, presents no toxic effect at a oral dose up to 2000 mg/kg body weight in rats [25,26]. Moreover, it possesses anticancer effects [27,28], prevents the development of hepatic fibrosis [29,30], and reduces toxicant-induced liver injury [8,11]. However, the limited solubility of quercetin in water and poor bioavailability in liver present a major problem for its administration as a chemopreventer.…”

Section: Discussionmentioning

confidence: 99%

“…Quercetin, a pigment (flavonoid) found in many plants and foods such as wine, apple, onions, green tea, berries and some herbs, has wide bioactivity, 3 including anti-oxidative, anti-fibrotic and anti-inflammatory effects [4,5,6,7]. Its protective effect on liver injury was previously identified [8,9,10,11]. However, quercetin has poor water solubility, so it cannot accumulate well in the liver.…”

Section: Introductionmentioning

confidence: 99%

Protective and Therapeutic Effects of Nanoliposomal Quercetin on Acute Liver Injury in Rats

Liu

Zhang

Liu

et al. 2020

Preprint

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Background Quercetin, a pigment (flavonoid) found in many plants and foods, has good effects on protecting liver function but poor solubility and bioavailability in vivo. A drug delivery system can improve the accumulation and bioavailability of quercetin in liver. Objective In this study, we used liposomal nanoparticles to entrap quercetin and evaluated its protective and therapeutic effects on drug-induced liver injury in rats. Design The nanoliposomal quercetin was prepared by a thin film evaporation-high pressure homogenization method and characterized by morphology, particle size and drug content. Acute liver injury was induced in rats by composite factors, including carbon tetrachloride injection, high-fat corn powder intake and ethanol drinking. After pure quercetin or nanoliposomal quercetin treatment, liver function was evaluated by detecting serum levels of glutamic-pyruvic transaminase (GPT), glutamic-oxal acetic transaminase (GOT) and direct bilirubin (DBIL). Histology of injured liver tissues was evaluated by hematoxylin and eosin staining. Results and discussion On histology, liposomal nanoparticles loading quercetin were evenly distributed spherical particles. The nanoliposomal quercetin showed high bioactivity and bioavailability in rat liver and markedly attenuated the liver index and pathologic changes in injured liver tissue. With nanoliposomal quercetin treatment, the serum levels of GPT, GOT and DBIL were significantly better than treated with pure quercetin. Using liposomal nanoparticles to entrap quercetin might be an effective strategy to reduce hepatic injury and protect hepatocytes against damage. Conclusions Liposomal nanoparticles may improve the solubility and bioavailability of quercetin in liver. Furthermore, nanoliposomal quercetin could effectively protect rats against acute liver injury and may be a new hepatoprotective and therapeutic agent for patients with liver diseases.

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“…Quercetin is a natural flavonoid with well-known antioxidant capacity [20]. Quercetin has been reported to alleviate liver injury induced by various hepatotoxicants, including pyrrolizidine alkaloids, nickel, lipopolysaccharides/D-galactosamine, triptolide, and carbon tetrachloride [21][22][23][24][25][26]. Our previous in vitro study showed that quercetin reversed TSN-induced cytotoxicity in human normal liver L-02 cells [27], indicating the potential detoxification of quercetin against TSN-induced liver injury.…”

Section: Introductionmentioning

confidence: 99%

Quercetin attenuates toosendanin-induced hepatotoxicity through inducing the Nrf2/GCL/GSH antioxidant signaling pathway

Yao

Huang

et al. 2018

Acta Pharmacol Sin

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Toosendanin (TSN) is the main active compound in Toosendan Fructus and Meliae Cortex, two commonly used traditional Chinese medicines. TSN has been reported to induce hepatotoxicity, but its mechanism remains unclear. In this study, we demonstrated the critical role of nuclear factor erythroid 2-related factor 2 (Nrf2) in protecting against TSN-induced hepatotoxicity in mice and human normal liver L-02 cells. In mice, administration of TSN (10 mg/kg)-induced acute liver injury evidenced by increased serum alanine/aspartate aminotransferase (ALT/AST) and alkaline phosphatase (ALP) activities, and total bilirubin (TBiL) content as well as the histological changes. Furthermore, TSN markedly increased liver reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and decreased liver glutathione (GSH) content and Nrf2 expression. In L-02 cells, TSN (2 μM) time-dependently reduced glutamate-cysteine ligase (GCL) activity and cellular expression of the catalytic/modify subunit of GCL (GCLC/GCLM). Moreover, TSN reduced cellular GSH content and the increased ROS formation, and time-dependently decreased Nrf2 expression and increased the expression of the Nrf2 inhibitor protein kelch-like ECH-associated protein-1 (Keap1). Pre-administration of quercetin (40, 80 mg/kg) effectively inhibited TSN-induced liver oxidative injury and reversed the decreased expression of Nrf2 and GCLC/GCLM in vivo and in vitro. In addition, the quercetin-provided protection against TSN-induced hepatotoxicity was diminished in Nrf2 knock-out mice. In conclusion, TSN decreases cellular GSH content by reducing Nrf2-mediated GCLC/GCLM expression via decreasing Nrf2 expression. Quercetin attenuates TSN-induced hepatotoxicity by inducing the Nrf2/GCL/GSH antioxidant signaling pathway. This study implies that inducing Nrf2 activation may be an effective strategy to prevent TSN-induced hepatotoxicity.

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The involvement of sirtuin 1 and heme oxygenase 1 in the hepatoprotective effects of quercetin against carbon tetrachloride-induced sub-chronic liver toxicity in rats

Cited by 26 publications

References 61 publications

Quercetin protected against isoniazide‐induced HepG2 cell apoptosis by activating the SIRT1/ERK pathway

Quercetin protected against isoniazide‐induced HepG2 cell apoptosis by activating the SIRT1/ERK pathway

Protective and Therapeutic Effects of Nanoliposomal Quercetin on Acute Liver Injury in Rats

Quercetin attenuates toosendanin-induced hepatotoxicity through inducing the Nrf2/GCL/GSH antioxidant signaling pathway

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