Effects of ivermectin and its combination with alpha lipoic acid on expression of IGFBP-3 and HSPA1 genes and male rat fertility

El-Maddawy, Zeynab Kh.; Naby, Walaa S.H. Abd El

doi:10.1111/and.12891

Cited by 13 publications

(13 citation statements)

References 46 publications

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“…Indeed, previous studies indicated that ivermectin exhibited adverse effects on male reproduction. [33][34][35] Ivermectin treatment caused a reversible reduction of testicular volume and seminiferous tubular diameter, and disturbed the spermatogenesis in rats, all while not affecting the production of testosterone. 34 Ivermectin injection induced a reduction of sperm number, sperm motility as well as serum testosterone level in rats.…”

Section: Discussionmentioning

confidence: 98%

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Synergistic effects of EP‐1 and ivermectin mixture (iEP‐1) to control rodents and their ectoparasites

Liu

Ren

Wan

et al. 2022

Pest Management Science

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BACKGROUND: Ectoparasites of rodents play significant roles in disease transmission to humans. Conventional poisoning potentially reduces the population densities of rodents, however, they may increase the ectoparasite loads on the surviving hosts. EP-1 has been shown to have anti-fertility effects on many rodent species, while ivermectin is effective in controlling ectoparasites. In this study, we examined the combined effects of EP-1 and ivermectin mixture (iEP-1) baits on rodents and their corresponding flea/tick loads. RESULTS: In males, the weight of testis, epididymis, and seminiferous vesicle were reduced to less than 33%, 25%, and 17%, respectively, compared to the control group following administration of iEP-1 for 7 days. The weight of the uterus increased by approximately 75%. After 5 days of iEP-1 intake, all ticks were killed, whereas 94% of fleas on mice died after 3 days of bait intake. In the field test near Beijing, the flea index was reduced by more than 90% after 7 days of iEP-1 bait delivery. In a field test in Inner Mongolia, the weights of testis, epididymis, and seminiferous vesicle were significantly reduced by 27%, 32%, and 57%, respectively, 2 weeks after iEP-1 bait delivery. Approximately 36% rodents exhibited obvious uterine oedema accompanied by a weight increase of about 150%. The flea index was reduced by over 90%. CONCLUSION: Our results indicated that iEP-1 is a promising treatment for reducing the abundance of both small rodents and their ectoparasites; this will be effective for managing rodent damage and transmission of rodent-borne diseases associated with fleas and ticks.

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Section: Discussionmentioning

confidence: 98%

“…[33][34][35] Injection of ivermectin in rats significantly decreased the testosterone level, sperm number and motility, and testes weight. 33,35 Ivermectin injection significantly suppressed spermatogenesis of rats. 34 Thus, it is likely that ivermectin would facilitate the anti-fertility effect with EP-1 in sterilizing rodents.…”

Section: Introductionmentioning

confidence: 97%

Synergistic effects of EP‐1 and ivermectin mixture (iEP‐1) to control rodents and their ectoparasites

Liu

Ren

Wan

et al. 2022

Pest Management Science

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“…It has been shown previously that ALA mediates its beneficial effects by activating the HSR. However, these investigations were focused on a limited set of HSPs; namely HSP25, HSP60, HSP72, HSF1 and GRP75 27,33,34 . Our previous in vivo and in vitro investigations confirmed a novel role of DNAJB3 in reducing metabolic stress, improving insulin signaling and promoting glucose uptake 29,30 .…”

Section: Resultsmentioning

confidence: 99%

Alpha lipoic acid attenuates ER stress and improves glucose uptake through DNAJB3 cochaperone

Diané

Mahmoud

Bensmail

et al. 2020

Sci Rep

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Persistent ER stress, mitochondrial dysfunction and failure of the heat shock response (HSR) are fundamental hallmarks of insulin resistance (IR); one of the early core metabolic aberrations that leads to type 2 diabetes (T2D). The antioxidant α-lipoic acid (ALA) has been shown to attenuate metabolic stress and improve insulin sensitivity in part through activation of the heat shock response (HSR). However, these studies have been focused on a subset of heat shock proteins (HSPs). In the current investigation, we assessed whether ALA has an effect on modulating the expression of DNAJB3/HSP40 cochaperone; a potential therapeutic target with a novel role in mitigating metabolic stress and promoting insulin signaling. Treatment of C2C12 cells with 0.3 mM of ALA triggers a significant increase in the expression of DNAJB3 mRNA and protein. A similar increase in DNAJB3 mRNA was also observed in HepG2 cells. We next investigated the significance of such activation on endoplasmic reticulum (ER) stress and glucose uptake. ALA pre-treatment significantly reduced the expression of ER stress markers namely, GRP78, XBP1, sXBP1 and ATF4 in response to tunicamycin. In functional assays, ALA treatment abrogated significantly the tunicamycin-mediated transcriptional activation of ATF6 while it enhanced the insulin-stimulated glucose uptake and Glut4 translocation. Silencing the expression of DNAJB3 but not HSP72 abolished the protective effect of ALA on tunicamycin-induced ER stress, suggesting thus that DNAJB3 is a key mediator of ALA-alleviated tunicamycin-induced ER stress. Furthermore, the effect of ALA on insulin-stimulated glucose uptake is significantly reduced in C2C12 and HepG2 cells transfected with DNAJB3 siRNA. In summary, our results are supportive of an essential role of DNAJB3 as a molecular target through which ALA alleviates ER stress and improves glucose uptake.

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“…Although the study identified a decrease in sperm parameters including sperm motility and count, it possessed serious limitations, including a lack of control group. Some other studies have shown ivermectin to be gonadotoxic in animal models 61 , but there have been no definitive findings to suggest that ivermectin is associated with male infertility in humans. Attention should be brought to the consequences that future medications used for COVID-19 treatment may have on fertility.…”

Section: Covid-19 Medical Interventionsmentioning

confidence: 96%

Impact of COVID-19 on Male Fertility

Collins¹,

Zhao²,

Zhu³

et al. 2022

Urology

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COVID-19, the clinical condition caused by the SARS-CoV-2 virus, has been associated with massive cytokine storm and damage to multiple organ systems. Although evidence for the detection of SARS-CoV-2 virus in the testis remains scarce, testicular damage and dysregulation of gonadotropins associated with inflammation has been reported. Additionally, as a result of the rapidly evolving pandemic, frequently updated medical interventions and public policies leading to delays of care can play a role in fertility. This narrative review aims to summarize the current literature on how COVID-19 may influence male fertility.

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Effects of ivermectin and its combination with alpha lipoic acid on expression of IGFBP-3 and HSPA1 genes and male rat fertility

Cited by 13 publications

References 46 publications

Synergistic effects of EP‐1 and ivermectin mixture (iEP‐1) to control rodents and their ectoparasites

Synergistic effects of EP‐1 and ivermectin mixture (iEP‐1) to control rodents and their ectoparasites

Alpha lipoic acid attenuates ER stress and improves glucose uptake through DNAJB3 cochaperone

Impact of COVID-19 on Male Fertility

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