Lycopene abrogates di-(2-ethylhexyl) phthalate induced testicular injury by modulating oxidative, endocrine and inflammatory changes in mice

Bahrami, Nosrat; Mehrzadi, Saeed; Goudarzi, Mehdi; Mansouri, Esrafil; Fatemi, Iman

doi:10.1016/j.lfs.2018.06.009

Cited by 34 publications

(21 citation statements)

References 35 publications

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“…Consistent with this finding, MOe exerted a protective role on antioxidant status in heart muscle and lipid peroxidation in streptozocin-induced diabetic models in rats [ 64 ]. The observed antioxidant effect of MO is comparable to that tested by other antioxidant molecules: alpha lipoic acid, melatonin, lycopene, and silymarin, that have shown a protective effect against oxidative stress induced by DEHP [ 65 , 66 , 67 , 68 ].…”

Section: Discussionsupporting

confidence: 58%

Moringa oleifera Protects SH-SY5YCells from DEHP-Induced Endoplasmic Reticulum Stress and Apoptosis

et al. 2021

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Moringa oleifera (MO) is a medicinal plant that has been shown to possess antioxidant, anticarcinogenic and antibiotic activities. In a rat model, MO extract (MOe) has been shown to have a protective effect against brain damage and memory decline. As an extending study, here, we have examined the protective effect of MOe against oxidative stress and apoptosis caused in human neuroblastome (SH-SY5Y) cells by di-(2-ethylhexyl) phthalate (DEHP), a plasticizer known to induce neurotoxicity. Our data show that MOe prevents oxidative damage by lowering reactive oxygen species (ROS) formation, restoring mitochondrial respiratory chain complex activities, and, in addition, by modulating the expression of vitagenes, i.e., antioxidant proteins Nrf2 and HO-1. Moreover, MOe prevented neuronal damage by partly inhibiting endoplasmic reticulum (ER) stress response, as indicated by decreased expression of CCAAT-enhancer-binding protein homologous protein (CHOP) and Glucose-regulated protein 78 (GRP78) proteins. MOe also protected SH-SY5Y cells from DEHP-induced apoptosis, preserving mitochondrial membrane permeability and caspase-3 activation. Our findings provide insight into understanding of molecular mechanisms involved in neuroprotective effects by MOe against DEHP damage.

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Section: Discussionsupporting

confidence: 58%

Moringa oleifera Protects SH-SY5YCells from DEHP-Induced Endoplasmic Reticulum Stress and Apoptosis

et al. 2021

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“…As an environmental endocrine disruptor, DEHP has toxic effects in vertebrates. Increasing evidence manifested that DEHP can cause oxidative stress, inflammation and dysfunction in different glands (Zhao et al, 2019;Bahrami et al, 2018). Inhibition of oxidative stress and inflammation by regulating their corresponding signaling pathways would be an effective therapeutic treatment assuaging DEHP-induced thyrotoxicity in inflammasomes activation.…”

Section: Discussionmentioning

confidence: 99%

Rosmarinic acid alleviates di-2-ethylhexyl phthalate (DEHP) -induced thyroid dysfunction via multiple inflammasomes activation

Xiaolin

2020

J. Toxicol. Sci.

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DEHP (di-2-ethylhexyl phthalate), an environmental endocrine disruptor, is widely used in industrial products, particularly as plasticizers and softeners which could disrupt the function of the hypothalamic-pituitary-thyroid (HPT) axis. Rosmarinic acid (RA) possesses potential antioxidant and anti-inflammatory capacities in disease models. Nevertheless, evidence on the association between DEHP-induced thyroid dysfunction and inflammation, as well as the molecular mechanism underlying the protective effects of RA-mitigated DEHP-induced thyroid injury remains inconclusive. Male Sprague Dawley (SD) rats were intragastrically administered DEHP (150 mg/kg, 300 mg/kg, 600 mg/kg) once a day for 90 consecutive days. Also, FRTL-5 cells were treated with a wide range of DEHP concentrations (10 -8 , 10 -7 , 10 -6 , 10 -5 , 10 -4 , 10 -3 , 10 -2 M) for 24 hr. Subsequently, RA (50 μM) was administered for 24 hr before 10 -4 M DEHP challenge. We found that DEHP induced thyroid damage and inflammatory infiltration in vivo. In addition, we showed that DEHP triggered inflammatory cell death, which is mediated by multiple inflammasomes. Moreover, RA, pyroptosis inhibitor (Ac-YVAD-cmk) and antioxidant inhibitor (NAC) treatment significantly alleviated DEHP-induced thyrocyte death, suppressing pro-inflammatory cytokine production, inhibiting multiple inflammasomes activation and attenuating thyrocyte death, respectively. Collectively, our results reveal that a critical role of inflammasomes activation in DEHP-induced thyroid injury, and suggest that RA confers protection against DEHP-induced thyroid inflammation, and facilitating control of the effects of DEHP after given pyroptosis inhibitor or antioxidant inhibitor. These results indicate that it should be possible to provide novel insights into toxicologically and pharmacologically targeting this molecule to DEHP-induced inflammation.

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“…DEHP promotes the development of immune responses and subsequent male infertility through increasing the expression of inflammatory mediators (Larsen et al, 2007; Hirai et al, 2015). Recent studies have reported that DEHP increased the production of inflammatory cytokines such as TNF-α and IL-1β in mice testes (Bahrami et al, 2018a,b). In agreement with previous studies, our results showed that DEHP elevated serum TNF-α, IL-1β, and IL-6 levels and increased the mRNA expression of TNF-α, IL-1β, and IL-6 in the testes.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, oxidative stress has been recognized as a critical mechanism underlying DEHP-induced testicular injury. Although many natural antioxidants, such as lycopene, quercetin, and curcumin (Zhang et al, 2014; Abdel-Kawi et al, 2016; Bahrami et al, 2018b), have been used to prevent DEHP-induced testicular toxicity though inhibiting oxidative stress. The exact mechanisms of DEHP-induced reproductive toxicity are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Lactobacillus plantarum TW1-1 Alleviates Diethylhexylphthalate-Induced Testicular Damage in Mice by Modulating Gut Microbiota and Decreasing Inflammation

Tian

Feng

et al. 2019

Front. Cell. Infect. Microbiol.

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Diethylhexylphthalate (DEHP), acting as an endocrine disruptor, disturbed reproductive health. Here, we evaluated the effects of Lactobacillus plantarum TW1-1 ( L. plantarum TW1-1) on DEHP-induced testicular damage in adult male mice. Results showed that oral supplementation of L. plantarum TW1-1 significantly increased the serum testosterone concentration, enhanced the semen quality, and attenuated gonad development defects in DEHP-exposed mice. L. plantarum TW1-1 also alleviated DEHP-induced oxidative stress and inflammatory responses by decreasing the mRNA expression and serum protein concentration of different inflammatory factors [tumor necrosis factor-α, interleukin (IL)-1β and IL-6]. Furthermore, L. plantarum TW1-1 significantly reduced DEHP-induced intestinal hyper-permeability and the increase in the serum lipopolysaccharide level. Gut microbiota diversity analysis revealed that L. plantarum TW1-1 shifted the DEHP-disrupted gut microbiota to that of the control mice. At phylum level, L. plantarum TW1-1 reversed DEHP-induced Bacteroidetes increase and Firmicutes decrease, and restored Deferribacteres in DEHP-exposed mice. Spearman's correlation analysis showed that Bacteroidetes, Deferribacteres , and Firmicutes were associated with DEHP-induced testicular damage. In addition, the ratio of Firmicutes to Bacteroidetes (Firm/Bac ratio) significantly decreased from 0.28 (control group) to 0.13 (DEHP-exposed group), which was restored by L. plantarum TW1-1 treatment. Correlation analysis showed that the Firm/Bac ratio was negatively correlated with testicular damage and inflammation. These findings suggest that L. plantarum TW1-1 prevents DEHP-induced testicular damage via modulating gut microbiota and decreasing inflammation.

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Lycopene abrogates di-(2-ethylhexyl) phthalate induced testicular injury by modulating oxidative, endocrine and inflammatory changes in mice

Cited by 34 publications

References 35 publications

Moringa oleifera Protects SH-SY5YCells from DEHP-Induced Endoplasmic Reticulum Stress and Apoptosis

Moringa oleifera Protects SH-SY5YCells from DEHP-Induced Endoplasmic Reticulum Stress and Apoptosis

Rosmarinic acid alleviates di-2-ethylhexyl phthalate (DEHP) -induced thyroid dysfunction via multiple inflammasomes activation

Lactobacillus plantarum TW1-1 Alleviates Diethylhexylphthalate-Induced Testicular Damage in Mice by Modulating Gut Microbiota and Decreasing Inflammation

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