Pentoxifylline promotes spermatogenesis via upregulation of the Nrf2-ARE signalling pathway in a mouse model of germ-cell apoptosis induced by testicular torsion–detorsion

Akanji, Omotosho Dhulqarnain; Hassanzadeh, Gholamreza; Malekzadeh, Mehrnoush; Khanmohammadi, Nasrin; Khanezad, Maryam; Sadeghiani, Ghazaleh; Rastegar, Tayebeh

doi:10.1071/rd22168

Cited by 2 publications

References 44 publications

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Effects of Lupeol On Experimental Testicular Ischemia/Reperfusion Damage in Rats

Azzam,

Karabulut,

Kaya

et al. 2024

Preprint

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Objective Infertility and organ loss are possible outcomes of testicular torsion, a urological emergency. We sought to demonstrate the impact of lupeol on testicular ischemia reperfusion damage in this investigation.Methods 30 adult male Spraque Dawley rats were randomized and divided as Control(C), Lupeol(L), Ischemia(I), Treatment 1(T1) and Treatment 2(T2) groups. In the study groups, detorsion was applied to the left testicles by creating 720 degree testicular torsion for 2 hours. While 100 mg/kg Lupeol was injected intraperitoneally in the T1 and T2 groups 30 min. before and immediately after testicular detorsion. At the sixth hour, samples of blood and testicular tissue were obtained from every rat. Measurements were taken of serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) tissue glutathione (GSH), malondialdehyde (MDA), and caspase 3. Histopathological analysis was used to evaluate the Johnsen Tubular Biopsy Score (JTBS).Results It was observed that Caspase 3, MDA, IL-6 and TNF-ɑ values, which increased in Group I compared to the Group C, decreased more significantly in both treatment groups and especially in the GroupT1 group (p = 0.001, only p = 0.768 for TNF-ɑ). GSH levels was decreased in Group I, increased more significantly in both treatment groups and especially in the GroupT1 group. JTBS improvement was observed in both treatment groups (p = 0.001).Conclusion In this study, where Lupeol was used for the first time in an experimental testicular torsion model, its antioxidant, anti-inflammatory and anti-apoptotic effects, as well as its histopathological damage-reducing and protective effects, were demonstrated.

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Effects of Lupeol On Experimental Testicular Ischemia/Reperfusion Damage in Rats

Azzam,

Karabulut,

Kaya

et al. 2024

Preprint

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Bioactive Compounds Protect Mammalian Reproductive Cells from Xenobiotics and Heat Stress-Induced Oxidative Distress via Nrf2 Signaling Activation: A Narrative Review

Khan,

Huang

et al. 2024

Antioxidants

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Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body’s antioxidant defenses. It poses a significant threat to the physiological function of reproductive cells. Factors such as xenobiotics and heat can worsen this stress, leading to cellular damage and apoptosis, ultimately decreasing reproductive efficiency. The nuclear factor erythroid 2–related factor 2 (Nrf2) signaling pathway plays a crucial role in defending against oxidative stress and protecting reproductive cells via enhancing antioxidant responses. Dysregulation of Nrf2 signaling has been associated with infertility and suboptimal reproductive performance in mammals. Recent advancements in therapeutic interventions have underscored the critical role of Nrf2 in mitigating oxidative damage and restoring the functional integrity of reproductive cells. In this narrative review, we delineate the harmful effects of heat and xenobiotic-induced oxidative stress on reproductive cells and explain how Nrf2 signaling provides protection against these challenges. Recent studies have shown that activating the Nrf2 signaling pathway using various bioactive compounds can ameliorate heat stress and xenobiotic-induced oxidative distress and apoptosis in mammalian reproductive cells. By comprehensively analyzing the existing literature, we propose Nrf2 as a key therapeutic target for mitigating oxidative damage and apoptosis in reproductive cells caused by exposure to xenobiotic exposure and heat stress. Additionally, based on the synthesis of these findings, we discuss the potential of therapies focused on the Nrf2 signaling pathway to improve mammalian reproductive efficiency.

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Pentoxifylline promotes spermatogenesis via upregulation of the Nrf2-ARE signalling pathway in a mouse model of germ-cell apoptosis induced by testicular torsion–detorsion

Cited by 2 publications

References 44 publications

Effects of Lupeol On Experimental Testicular Ischemia/Reperfusion Damage in Rats

Effects of Lupeol On Experimental Testicular Ischemia/Reperfusion Damage in Rats

Bioactive Compounds Protect Mammalian Reproductive Cells from Xenobiotics and Heat Stress-Induced Oxidative Distress via Nrf2 Signaling Activation: A Narrative Review

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