Eucalyptol relieves the toxicity of diisobutyl phthalate in Ctenopharyngodon idellus kidney cells through Keap1/Nrf2/HO-1 pathway: Apoptosis-autophagy crosstalk and immunoregulation

Liu, Huanyi; Sun, Wenying; Zhu, Huijun; Guo, Junyi; Liu, Min; Xu, Shiwen

doi:10.1016/j.fsi.2022.09.056

Cited by 17 publications

(10 citation statements)

References 53 publications

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“…68 The KEAP1/NRF2 complex has been identified as an important way to stimulate the autophagy process in immune cells and in prostate cancer. 68,69 Interestingly, according to Wang, 70 Animal and human studies show that maternal exposure to phthalates influences prostatic disorders in offspring. 21,71,72 The increased risk of developing prostatic diseases has been related to the genetic and epigenetic perturbations 15,21,73 reinforcing the hypothesis that maternal phthalates exposure increase the susceptibility of the offspring to prostate cancer by post-transcriptional and phenotypic alterations.…”

Section: Discussionmentioning

confidence: 99%

“…In prostate cancer, overexpression of P62/keap1/Nrf2 pathways triggers transcriptional blockade of targets associated with reactive oxygen species response, cell proliferation, and invasion 68 . The KEAP1/NRF2 complex has been identified as an important way to stimulate the autophagy process in immune cells and in prostate cancer 68,69 . Interestingly, according to Wang, 70 post‐transcriptional levels of miRNA 141–3p are responsible for controlling KEAP1/NRF2 signaling in patients with prostatitis 70 …”

Section: Discussionmentioning

confidence: 99%

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In silico investigation of the role of miRNAs in a possible developmental origin of prostate cancer in F1 and F2 offspring of mothers exposed to a phthalate mixture

Aquino,

Fioretto,

Alonso‐Costa

et al. 2024

Environmental Toxicology

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A previous study using miRNA sequencing revealed that exposure to a mixture of phthalates during pregnancy and lactation dysregulated rno‐miR‐184 and rno‐miR‐141‐3p in the ventral prostate (VP) of offspring. Here, rno‐miR‐184 and rno‐miR‐141‐3 expressions were obtained by RT‐qPCR in the VP of F1 males as well as in F2 offspring, aiming to establish a relationship with possible oncogenic targets through in silico analyses with multigenerational approach. Additionally, some targets were measured by western blots to highlight a possible relationship between the deregulated miRNAs and some of their targets. VP samples from rats exposed to a mixture of phthalates maternally during pregnancy and lactation (GD10 to PND21‐F1) and VP from offspring (F2) were examined. The phthalate mixture at both concentrations (20 μg and 200 mg/kg/day) increased the expression of both miRNAs in the F1 (PND22 and 120) and F2 (descendants of F1‐treated males) prostate. Target prediction analysis revealed that both microRNAs are responsible for modulating the expression and synthesis of 40 common targets. A phthalate target association analysis and the HPA database showed an interesting relationship among these possible miRNAs modulated targets with prostate adenocarcinoma and other oncogenic processes. Western blots showed alteration in P63, P53, WNT5, and STAT3 expression, which are targeted by the miRNAs, in the VP of F1/F2 males. The data draw attention to the epigenetic modulation in the prostate of descendants exposed to phthalates and adds to one of the few currently found in the literature to point to microRNAs signature as biomarkers of exposure to plasticizers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

In silico investigation of the role of miRNAs in a possible developmental origin of prostate cancer in F1 and F2 offspring of mothers exposed to a phthalate mixture

Aquino,

Fioretto,

Alonso‐Costa

et al. 2024

Environmental Toxicology

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“…Of these, eucalyptol has a potential anti-obesity role as demonstrated by its inhibition of digestive enzymes, specifically α-amylase and pancreatic enzymes [ 51 ]. In addition, the antioxidant activity of eucalyptol has been reported [ 52 ]; however, the specific anti-diabetic effects of other compounds in the extract have not been evaluated. Further studies involving compound isolation and their activity are warranted.…”

Section: Discussionmentioning

confidence: 99%

Methanol extract of Elsholtzia fruticosa promotes 3T3-L1 preadipocyte differentiation

Shrestha,

Kim,

Shrestha

et al. 2024

J Anim Sci Technol

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Elsholtzia fruticosa (EF) is present in tropical regions throughout South Asian countries as well as the Himalayas. Although it has been used as a traditional medicine to treat digestive, respiratory, and inflammatory issues, its effect on preadipocyte differentiation is unknown. In this study, we examined the effects of a methanol extract prepared from EF on the differentiation of 3T3-L1 preadipocytes. Cell differentiation was assessed by microscopic observation and oil-red O staining. The expression of adipogenic and lipogenic genes, including PPARγ and C/EBPα , was measured by western blot analysis and quantitative real-time polymerase chain reaction (qRT–PCR), to provide insight into adipogenesis and lipogenesis mechanisms. The results indicated that EF promotes the differentiation of 3T3-L1 preadipocytes, with elevated lipid accumulation occurring in a concentration-dependent manner without apparent cytotoxicity. EF enhances the expression of adipogenic and lipogenic genes, including PPARγ , FABP4 , adiponectin , and FAS , at the mRNA and protein levels. The effect of EF was more pronounced during the early and middle stages of 3T3-L1 cell differentiation. Treatment with EF decreased C/EBP homologous protein (CHOP) mRNA and protein levels, while increasing C/EBPα and PPARγ expression. Treatment with EF resulted in the upregulation of cyclin E and CDK2 gene expression within 24 h, followed by a decrease at 48 h, demonstrating the early-stage impact of EF. A concomitant increase in cyclin-D1 levels was observed compared with untreated cells, indicating that EF modulates lipogenic and adipogenic genes through intricate mechanisms involving CHOP and cell cycle pathways. In summary, EF induces the differentiation of 3T3-L1 preadipocytes by increasing the expression of adipogenic and lipogenic genes, possibly through CHOP and cell cycle-dependent mechanisms.

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“…30 Eucalyptus (EUC) is an essential oil obtained from eucalyptus leaves, belonging to monoterpene oxides, which has multiple bioactivity, including antioxidant, antibacterial and anti-inflammatory. [31][32][33][34][35][36] Moreover, EUC also has liver protection. 37 Studies have found that EUC can reduce blood lipids and anti-inflammation in hypercholesterolemia zebrafish, can play an antioxidant activity in lipoprotein metabolism in vivo and in vitro, and reduce lipid accumulation in the zebrafish liver.…”

Section: Introductionmentioning

confidence: 99%

“…Eucalyptus (EUC) is an essential oil obtained from eucalyptus leaves, belonging to monoterpene oxides, which has multiple bioactivity, including antioxidant, antibacterial and anti‐inflammatory 31–36 . Moreover, EUC also has liver protection 37 .…”

Section: Introductionmentioning

confidence: 99%

Eucalyptol antagonized the apoptosis and immune dysfunction of grass carp hepatocytes induced by tetrabromobisphenol A by regulating ROS/ASK1/JNK pathway

Sun

Liu

Zhu

et al. 2023

Environmental Toxicology

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Tetrabromobisphenol A (TBBPA) is a common environmental pollutant which has multi‐organ toxicity to mammals. Eucalyptol (EUC) has super antioxidant biological activity. However, in this experimental study, we probed into the mechanism of toxic of TBBPA exposure on Grass carp hepatocytes (L8824 cells) and the antagonistic impact of EUC on TBBPA. We treated L8824 cells with 8 μg/ml TBBPA and/or 20 μM EUC for 24 h in this test research. The experiment results suggested that TBBPA exposure induced elevated levels of reactive oxygen species (ROS), led to oxidative stress, decreased SOD and CAT activities, decreased GSH and T‐AOC contents, exacerbated MDA accumulation, activated ASK1/JNK signaling pathway, and further increased the contents of mitochondrial dependent apoptosis pathway related indicators (Cyt‐C, Bax, Caspase 9, Caspase 3), while Bcl‐2 expression decreased. In addition, TBBPA exposure induced increased expression of TNF‐α, IL‐6, IL‐1β, and decreased expression of IL‐2, IFN‐γ, Hepcidin, β‐defensin, LEAP2. The oxidative stress level, ASK1/JNK signal pathway expression level, apoptosis ratio and cellular immune function of cells exposed to EUC alone did not change significantly. Combined exposure of TBBPA and EUC significantly reduced the proportion of apoptosis and restored cellular immune function. Therefore, these results suggest that EUC can effectively antagonize TBBPA‐induced apoptosis and immune dysfunction of L8824 cells by regulating ROS/ASK1/JNK signaling pathway.

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Eucalyptol relieves the toxicity of diisobutyl phthalate in Ctenopharyngodon idellus kidney cells through Keap1/Nrf2/HO-1 pathway: Apoptosis-autophagy crosstalk and immunoregulation

Cited by 17 publications

References 53 publications

In silico investigation of the role of miRNAs in a possible developmental origin of prostate cancer in F1 and F2 offspring of mothers exposed to a phthalate mixture

In silico investigation of the role of miRNAs in a possible developmental origin of prostate cancer in F1 and F2 offspring of mothers exposed to a phthalate mixture

Methanol extract of Elsholtzia fruticosa promotes 3T3-L1 preadipocyte differentiation

Eucalyptol antagonized the apoptosis and immune dysfunction of grass carp hepatocytes induced by tetrabromobisphenol A by regulating ROS/ASK1/JNK pathway

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