Protective effect of genistein pre-treatment on paraquat hepatotoxicity in rats

Semeñiuk, María Belén; Ceré, Lucila Inés; Ciriaci, Nadia; Bucci-Muñoz, María; Quiroga, Ariel D.; Luquita, Marcelo G.; Roma, Stella; Catania, Viviana A.; Mottino, Aldo D.; Rigalli, Juan Pablo; Ruiz, María Laura

doi:10.1016/j.taap.2021.115636

Cited by 4 publications

(6 citation statements)

References 55 publications

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“…(Cui et al 2017 ; Chae et al 2019 ; Tuli et al 2019 ; Garbiec et al 2022 ). In relation to liver disease, previous studies have revealed that genistein inhibits EGFR system and has a protective effect during the processes of acute and chronic liver disease (Rodriguez et al 2016 ; Tanjak et al 2018 ; Xin et al 2019 ; Semeniuk et al 2021 ). However, the mechanisms responsible related with the effects of genistein on the expression and phosphorylation of EGFR are not completely understood.…”

Section: Discussionmentioning

confidence: 99%

“…Genistein and CCL 4 were obtained from Sigma Chemical Co., St. Louis, MO. The genistein dose was chosen in accordance with previous results carried out in animals treated with this drug (Semeniuk et al 2021 ). After the treatments, animals were deprived of food, but not of water, for 12 h, and were sacrificed with pentobarbital sodium (150 mg/kg of body weight), i.p.).…”

Section: Methodsmentioning

confidence: 99%

“…Previously, this group have reported that genistein is able to modify liver fibrosis and improves liver function by inhibit EGFR expression in rats with fibrosis induced by chronic administration of carbon tetrachloride (Rodriguez et al 2016 ). Interestingly, several research groups have also described the hepatoprotective role of genistein in acute liver damage induced by chemicals (Kuzu et al 2007 ; Ali et al 2015 ; Semeniuk et al 2021 ). Therefore, the aim of the present study was to investigate the role of genistein on EGFR expression, phosphorylation and signaling pathway in a CCl 4 -induced subacute liver injury model of rats.…”

Section: Introductionmentioning

confidence: 99%

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EGF-receptor phosphorylation and downstream signaling are activated by genistein during subacute liver damage

et al. 2023

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The epidermal growth factor receptor (EGFR) plays an important role on hepatic protection in acute and chronic liver injury. The aim of this study was to investigate the role of genistein on EGFR expression, phosphorylation and signaling pathways in experimental subacute liver damage induced by carbon tetrachloride (CCl4). We used male Wistar rats that were randomly divided into four groups: (1) Control; (2) Genistein 5 mg/kg per oral; (3) Subacute liver damage induced by CCl4 4 mg/kg subcutaneously; and (4) Animals received CCl4 and genistein at the dosage indicated. The effect of genistein on EGFR expression, phosphorylation and signaling pathways were investigated by western blot and densitometric analyses. Histological changes were evaluated on slices stained with Hematoxylin-Eosin and Masson´s trichromic, as well as an immunohistochemical analysis for proliferating cell nuclear antigen (PCNA). Additionally, pro-inflammatory cytokines and liver enzymes were quantified. Our study showed that genistein increased EGFR expression, EGFR-specific tyrosine residues phosphorylation (pY1068-EGFR and pY84-EGFR), signal transducer and activator of transcription phosphorylation (pSTAT5), protein kinase B phosphorylation (pAKT) and PCNA in animals with CCl4-induced subacute liver damage. It was found a significant reduction of pro-inflammatory cytokines in serum from animals with subacute liver damage treated with genistein. Those effects were reflected in an improvement in the architecture and liver function. In conclusion, genistein can induce a transactivation of EGFR leading to downstream cell signaling pathways as early events associated with regeneration and hepatoprotection following subacute liver damage.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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EGF-receptor phosphorylation and downstream signaling are activated by genistein during subacute liver damage

et al. 2023

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“…In liver, genistein induced the expression and activity of the ATP binding cassette transporter P-glycoprotein. e compound activates estrogen receptors α and β due to its structural similarity to 17-β-estradiol [162]. Acute liver injury is normally manifested with alanine aminotransferase (ALT), to be highly elevated at more than three times the baseline level.…”

Section: Discussionmentioning

confidence: 99%

Natural Products for Cancer Therapy: A Review of Their Mechanism of Actions and Toxicity in the Past Decade

Abdalla

Subramaniam

Nyamathulla

et al. 2022

Journal of Tropical Medicine

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The ethnopharmacological information gathered over many centuries and the presence of diverse metabolites have made the medicinal plants as the prime source of drugs. Despite the positive attributes of natural products, there are many questions pertaining to their mechanism of actions and molecular targets that impede their development as therapeutic agents. One of the major challenges in cancer research is the toxicity exerted by investigational agents towards the host. An understanding of their molecular targets, underlying mechanisms can reveal their anticancer efficacy, help in optimal therapeutic dose selection, to mitigate their side effects and toxicity towards the host. The purpose of this review is to collate details on natural products that are recently been investigated extensively in the past decade for their anticancer potential. Besides, critical analysis of their molecular targets and underlying mechanisms on multiple cancer cell lines, an in-depth probe of their toxicological screening on rodent models is outlined as well to observe the prevalence of their toxicity towards host. This review can provide valuable insights for researchers in developing methods, strategies during preclinical and clinical evaluation of anticancer candidates.

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“…Therefore, the liver has been suggested as a major target for PQ poisoning. In experimental animals, histopathological alterations, oxidative stress damage marker expressions (such as GSH depletion and lipidperoxidation production), and apoptosis in the liver were observed after administration of PQ ( El-Boghdady et al, 2017 , Semeniuk et al, 2021 , Shi et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Roles of oxidative stress/JNK/ERK signals in paraquat-triggered hepatic apoptosis

Lee,

Fang,

Kuo

et al. 2024

Current Research in Toxicology

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Protective effect of genistein pre-treatment on paraquat hepatotoxicity in rats

Cited by 4 publications

References 55 publications

EGF-receptor phosphorylation and downstream signaling are activated by genistein during subacute liver damage

EGF-receptor phosphorylation and downstream signaling are activated by genistein during subacute liver damage

Natural Products for Cancer Therapy: A Review of Their Mechanism of Actions and Toxicity in the Past Decade

Roles of oxidative stress/JNK/ERK signals in paraquat-triggered hepatic apoptosis

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