A potential mechanism associated with lead-induced testicular toxicity in rats

El-Magd, Mohammed A.; Kahilo, Khaled; Nasr, Nouha; Kamal, Tarek; Shukry, Mustafa; Saleh, Ayman A.

doi:10.1111/and.12750

Cited by 61 publications

(47 citation statements)

References 44 publications

(64 reference statements)

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“…57 Our findings are in agreement with others who reported downregulation of testicular steroidogenic enzymes by Pb exposure. 23,49,58 The reduced levels of these hormones in conjunction with the decreased expression of steroidogenic genes confirm the toxicity of Pb on endocrine and reproductive organs. 13,48 Interestingly, UMB prevented the negative impact of Pb on the pituitary-gonadal axis evidenced by the elevated serum FSH, LH and testosterone levels.…”

Section: Discussionmentioning

confidence: 79%

“…Our findings are in the line with the findings of other investigators who reported disrupted pituitary-gonadal axis by Pb exposure. 46,48,49 LH is an important stimulator for testosterone secretion from testicular Leydig cells and adequate amount of testosterone is essential for the structural and functional integrity of reproductive organs as well as to maintain the structure and function of male accessory glands. FSH secretion is necessary for the normal spermatogenesis as it stimulates the proliferation, maturation, and function of Sertoli cells to produce signals for the initiation and maintenance of germ cells.…”

Section: Discussionmentioning

confidence: 99%

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<p>Umbelliferone Inhibits Spermatogenic Defects and Testicular Injury in Lead-Intoxicated Rats by Suppressing Oxidative Stress and Inflammation, and Improving Nrf2/HO-1 Signaling</p>

Alotaibi¹,

Al-Joufi²,

Seif³

et al. 2020

DDDT

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Introduction: Lead (Pb) is an environmental toxic metal that threatens human health. Umbelliferone (UMB) is a coumarin with known medicinal and protective properties against cytotoxicity. This study explored the ameliorative effect of UMB against Pb-induced testicular toxicity in rats, focusing on steroidogenesis, oxidative stress and inflammation. Materials and Methods: Rats received lead acetate (50 mg/kg) and UMB (25, 50 or 100 mg/kg) via oral gavage for 4 weeks. Results: Pb-intoxicated rats exhibited testicular tissue injury and decreased serum levels of LH, FSH and testosterone. The count, viability, motility and normal morphology of the sperms were decreased accompanied with downregulated steroidogenesis markers in Pbinduced group. UMB prevented testicular injury, increased serum levels of LH, FSH and testosterone, upregulated steroidogenesis markers and improved the semen quality. In addition, UMB attenuated oxidative stress and oxidative DNA damage, downregulated the expression of pro-inflammatory mediators and Bax, boosted antioxidant defenses and Bcl-2, and upregulated Nrf2/HO-1 signaling in Pb-intoxicated rats. Conclusion: UMB prevents Pb-induced testicular injury by suppressing oxidative damage, inflammation and cell death, and boosting antioxidant defenses, Nrf2/HO-1 signaling and pituitary-gonadal axis. Thus, UMB may represent a protective and cost-effective agent against Pb testicular toxicity, pending further investigations to elucidate other underlying mechanisms.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

<p>Umbelliferone Inhibits Spermatogenic Defects and Testicular Injury in Lead-Intoxicated Rats by Suppressing Oxidative Stress and Inflammation, and Improving Nrf2/HO-1 Signaling</p>

Alotaibi¹,

Al-Joufi²,

Seif³

et al. 2020

DDDT

View full text Add to dashboard Cite

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“…The supernatants were used to measure the concentration of the lipid peroxidation biomarker malondialdehyde (MDA) and the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) using commercial kits (Bio-Diagnostics Co, Cairo, Egypt) as previously described. 22 …”

Section: Methodsmentioning

confidence: 99%

Therapeutic Effect of Camel Milk and Its Exosomes on MCF7 Cells In Vitro and In Vivo

Badawy

El-Magd

AlSadrah³

2018

Integr Cancer Ther

117

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Background/Objectives: In the Middle East, people consume camel milk regularly as it is believed to improve immunity against diseases and decrease the risk for cancer. Recently, it was noted that most of the beneficial effects of milk come from their nanoparticles, especially exosomes. Herein, we evaluated the anticancer potential of camel milk and its exosomes on MCF7 breast cancer cells (in vitro and in vivo) and investigated the possible underlying molecular mechanism of action. Methods/Results: Administration of camel milk (orally) and its exosomes (orally and by local injection) decreased breast tumor progression as evident by (a) higher apoptosis (indicated by higher DNA fragmentation, caspase-3 activity, Bax gene expression, and lower Bcl2 gene expression), (b) remarkable inhibition of oxidative stress (decrease in MDA levels and iNOS gene expression); (c) induction of antioxidant status (increased activities of SOD, CAT, and GPX), (d) notable reduction in expression of inflammation-(IL1b, NFκB), angiogenesis-(VEGF) and metastasis-(MMP9, ICAM1) related genes; and (e) higher immune response (high number of CD+4, CD+8, NK1.1 T cells in spleen). Conclusions: Overall, administration of camel milk–derived exosomes showed better anticancer effect, but less immune response, than treatment by camel milk. Moreover, local injection of exosomes led to better improvement than oral administration. These findings suggest that camel milk and its exosomes have anticancer effect possibly through induction of apoptosis and inhibition of oxidative stress, inflammation, angiogenesis and metastasis in the tumor microenvironment. Thus, camel milk and its exosomes could be used as an anticancer agent for cancer treatment.

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“…Liver tissues were homogenized using cold PBS, followed by centrifugation at 5000 g for 15 min at 4°C. The supernatants were used to measure the concentration of the lipid peroxidation biomarker MDA and the activity of antioxidant enzymes SOD, CAT, and GPX using commercial kits (Biodiagnostics Co., Cairo, Egypt, and Randox Laboratories Ltd., Crumlin, UK) and as previously described [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

Potential Effect of Exosomes Derived from Cancer Stem Cells and MSCs on Progression of DEN-Induced HCC in Rats

Alzahrani

El-Magd

Abdelfattah‐Hassan

et al. 2018

Stem Cells International

128

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Cross talk, mediated by exosomes, between normal stem cells and cancer stem cells (CSCs) in the tumor microenvironment has been given less attention so far. In addition, no publications are available in the literature that address the in vivo impact of exosomes derived from CSCs and mesenchymal stem cells (MSCs) on progression of long-term hepatocellular carcinoma (HCC). Herein, we hypothesized that transfer of exosomes among the cells in the HCC microenvironment could either induce or inhibit tumor growth and metastasis depending on their source. To check this hypothesis, we investigated the effect of exosomes coming from two different stem cell populations, hepatic CSCs and bone marrow (BM) MSCs, on progression of long-term DEN-induced HCC in rats and the involved underlying mechanisms. CSCs-exosomes induced a significant increase in liver relative weight and serum levels of cancer markers (AFP and GGT) and liver enzymes (ALT, AST, and ALP), intensive immunostaining for the HCC marker GST-P, and an increased number and area of tumor nodules as compared to HCC rats injected by PBS. CSCs-exosomes also decreased apoptosis (marked by downregulation of Bax and p53 and upregulation of Bcl2, and increased immunostaining of PCNA), increased angiogenetic activity (revealed by upregulation of VEGF), enhanced metastasis and invasiveness (indicated by upregulation of P13K and ERK proteins and their downstream target MMP9 and downregulation of TIMP1), and induced epithelial mesenchymal transition (marked by increased serum and hepatic level of TGFβ1 mRNA and protein). Notably, CSCs-exosomes also elevated HCC exosomal microRNA (miR) 21, exosomal long noncoding (lnc) RNA Tuc339, lncHEIH, and the HCC lncHOTAIR and decreased liver miR122 and HCC miRs (miR148a, miR16, and miR125b). All these cellular, functional, and molecular changes were reversed following injection of BM-MSCs-exosomes. However, both CSCs- and MSCs-exosomes failed to change the elevated oxidative stress or the inhibited antioxidant activities induced by HCC. Collectively, our results revealed a tumor stimulatory effect (induction of tumor growth, progression, and metastasis) for exosomes derived from CSCs and an inhibitory effect for exosomes derived from MSCs. These results provide valuable insight on the effect of CSCs- and MSCs-exosomes on HCC growth and progression in vivo, which may be helpful to understand the mechanism of HCC development.

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A potential mechanism associated with lead-induced testicular toxicity in rats

Cited by 61 publications

References 44 publications

<p>Umbelliferone Inhibits Spermatogenic Defects and Testicular Injury in Lead-Intoxicated Rats by Suppressing Oxidative Stress and Inflammation, and Improving Nrf2/HO-1 Signaling</p>

<p>Umbelliferone Inhibits Spermatogenic Defects and Testicular Injury in Lead-Intoxicated Rats by Suppressing Oxidative Stress and Inflammation, and Improving Nrf2/HO-1 Signaling</p>

Therapeutic Effect of Camel Milk and Its Exosomes on MCF7 Cells In Vitro and In Vivo

Potential Effect of Exosomes Derived from Cancer Stem Cells and MSCs on Progression of DEN-Induced HCC in Rats

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