Partial ameliorative effect of Moringa leaf ethanolic extract on the reproductive toxicity and the expression of steroidogenic genes induced by subchronic cadmium in male rats

Elblehi, Samar S.; Euony, Omnia I. El; El‐Nahas, Abeer F.

doi:10.1007/s11356-019-05607-y

Cited by 23 publications

(10 citation statements)

References 52 publications

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“…MO appears to possess various health-promoting properties. The flavonoids and polyphenols contained in MO confer neuroprotective, antioxidant, antibacterial, and anti-inflammatory properties [ 15 , 16 , 17 ].It has been demonstrated that MO extract (MOe) exerts protective effects on many organs, including liver, reproductive system, and central nervous system [ 18 , 19 , 20 ]. The use of MOe at different concentrations and incubation times makes this compound very versatile and itcan also have antiproliferative/anticancer activity [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…Disturbed gonadal and hormonal functions are also postulated to play a crucial role in the testicular toxicity induced by cadmium. Previous studies have described that several substrates that can regulate steroidogenesis and exert therapeutic effects on cadmium-induced testicular toxicity, such as Feijoa, Shilajit and Moringa leaf ethanolic extracts [ 6 , 28 , 29 ]. The present study was conducted to evaluate the effect of cadmium on steroidogenesis, the quality and quantity of sperm, and the inflammatory response in mice.…”

Section: Discussionmentioning

confidence: 99%

Letrozole protects against cadmium-induced inhibition of spermatogenesis via LHCGR and Hsd3b6 to activate testosterone synthesis in mice

Yao

Wan

Shi

et al. 2022

Reprod Biol Endocrinol

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The heavy metal cadmium is proposed to be one of the environmental endocrine disruptors of spermatogenesis. Cadmium-induced inhibition of spermatogenesis is associated with a hormone secretion disorder. Letrozole is an aromatase inhibitor that increases peripheral androgen levels and stimulates spermatogenesis. However, the potential protective effects of letrozole on cadmium-induced reproductive toxicity remain to be elucidated. In this study, male mice were administered CdCl2 (4 mg/kg BW) orally by gavage alone or in combination with letrozole (0.25 mg/kg BW) for 30 days. Cd exposure caused a significant decreases in body weight, sperm count, motility, vitality, and plasma testosterone levels. Histopathological changes revealed extensive vacuolization and decreased spermatozoa in the lumen. However, in the Cd + letrozole group, letrozole treatment compensated for deficits in sperm parameters (count, motility, and vitality) induced by Cd. Letrozole treatment significantly increased serum testosterone levels, which were reduced by Cd. Histopathological studies revealed a systematic array of all germ cells, a preserved basement membrane and relatively less vacuolization. For a mechanistic examination, RNA-seq was used to profile alterations in gene expression in response to letrozole. Compared with that in the Cd-treated group, RNA-Seq analysis showed that 214 genes were differentially expressed in the presence of letrozole. Gene ontology (GO) enrichment analysis and KEGG signaling pathway analysis showed that steroid biosynthetic processes were the processes most affected by letrozole treatment. Furthermore, we found that the expression of the testosterone synthesis-related genes LHCGR (luteinizing hormone/choriogonadotropin receptor) and Hsd3b6 (3 beta- and steroid delta-isomerase 6) was significantly downregulated in Cd‐treated testes, but these genes maintained similar expression levels in letrozole-treated testes as those in the control group. However, the transcription levels of inflammatory cytokines, such as IL-1β and IL-6, and oxidative stress-related genes (Nrf2, Nqo1, and Ho-1) showed no changes. The present study suggests that the potential protective effect of letrozole on Cd-induced reproductive toxicity might be mediated by the upregulation of LHCGR and Hsd3b6, which would beneficially increase testosterone synthesis to achieve optimum protection of sperm quality and spermatogenesis.

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“…Disturbed gonadal and hormonal functions are also believed to play a crucial role in the testicular toxicity induced by cadmium. Several studies have reported that several substrates that can regulate steroidogenesis can have therapeutic effects on cadmium-induced testicular toxicity, such as Feijoa, Shilajit and Moringa leaf ethanolic extracts [6, 23,24]. The present work was undertaken to evaluate the effect of cadmium on steroidogenesis, the quality and quantity of sperm, and the in ammatory response in mice.…”

Section: Discussionmentioning

confidence: 99%

Letrozole Protects Against Cadmium-induced Inhibition of Spermatogenesis via LHCGR and Hsd3b6 to Activate Testosterone Synthesis in Mice

Yao

Wan

Shi

et al. 2021

Preprint

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The heavy metal cadmium is believed to be one of the environmental endocrine disruptors of spermatogenesis. Cadmium-induced inhibition of spermatogenesis is associated with hormone secretion disorder. Letrozole is an aromatase inhibitor that can raise peripheral androgen levels and stimulate spermatogenesis. However, the potential protective effects of letrozole against cadmium-induced reproductive toxicity remain to be elucidated. In this study, male mice were administered CdCl2 (4 mg/kg BW) orally by gavage alone or in combination with letrozole (0.25 mg/kg BW) for 30 days. Cd exposure caused a significant decrease in body weight, sperm count, motility, vitality and plasma testosterone levels. Histopathological changes revealed extensive vacuolization and decreased spermatozoa in the lumen. However, in the Cd+letrozole group, letrozole treatment compensated for deficits in sperm parameters (count, motility, and vitality) induced by Cd. Letrozole treatment significantly increased serum testosterone levels, which were reduced by Cd. Histopathological studies revealed a systematic array of all germ cells, a preserved basement membrane and relatively less vacuolization. For mechanistic exploration, RNA-seq was used to profile alterations in gene expression in response to letrozole. Compared with that in the Cd-treated group, RNA-Seq analysis showed that 214 genes were differentially expressed in the presence of letrozole. Gene ontology (GO) enrichment analysis and KEGG signaling pathway analysis showed that steroid biosynthetic processes were the processes most affected by letrozole treatment. Furthermore, we found that the expression of the testosterone synthesis-related genes LHCGR (luteinizing hormone/choriogonadotropin receptor) and Hsd3b6 (3 beta- and steroid delta-isomerase 6) was significantly downregulated in Cd‐induced testes, but in letrozole-treated testes, these genes maintained similar expression levels as the control group. However, the transcription levels of inflammatory cytokines, such as IL-1β and IL-6, and oxidative stress-related genes (Nrf2, Nqo1, and Ho-1) showed no changes. The present study suggests that the protective potential of letrozole against Cd-induced reproductive toxicity might be due to upregulation of LHCGR and Hsd3b6, which could beneficially increase testosterone synthesis to achieve optimum protection in sperm quality and spermatogenesis.

show abstract

Partial ameliorative effect of Moringa leaf ethanolic extract on the reproductive toxicity and the expression of steroidogenic genes induced by subchronic cadmium in male rats

Cited by 23 publications

References 52 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

Letrozole protects against cadmium-induced inhibition of spermatogenesis via LHCGR and Hsd3b6 to activate testosterone synthesis in mice

Letrozole Protects Against Cadmium-induced Inhibition of Spermatogenesis via LHCGR and Hsd3b6 to Activate Testosterone Synthesis in Mice

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