Protection of Pentoxifylline against Testis Injury Induced by Intermittent Hypobaric Hypoxia

Yao, Chen; Li, Gang; Qian, Yongmei; Cai, Ming; Yin, Hong; Xiao, Li; Tang, Wei; Shi, Bingyi

doi:10.1155/2016/3406802

Cited by 22 publications

(20 citation statements)

References 47 publications

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“…Ferroptosis is a non-apoptotic form of regulated cell death triggered by inactivation of the lipid repair enzyme GPX4 and subsequent lipid peroxidation (4,37,39,40). Lipid peroxidation has routinely been described as a key factor that may lead to spermatogenesis disturbance by damaging Sertoli cells in testicular I/R injury (16,56). Iron-dependent lipid ROS-mediated I/R-induced renal cell ferroptosis and ROS generation-mediated OGd/R-induced Sertoli cell dysfunction have also been reported (4,16,17,(22)(23)(24)28,57).…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis is associated with oxygen-glucose deprivation/reoxygenation-induced Sertoli cell death

Zhao

et al. 2018

Int J Mol Med

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Sertoli cell death contributes to spermatogenesis impairment, which is associated with male infertility. Testicular ischemia‑reperfusion (I/R) injury induces the cell death of germ cells and Sertoli cells, whereas inhibition of cell death ameliorates acute testicular I/R damage. The aim of the present study was to investigate the mechanism of I/R stress-induced cell death in TM4 cells. Oxygen‑glucose deprivation and reoxygenation (OGD/R) was demonstrated to induce I/R injury and cell death in TM4 cells. Cell death was blocked by the reactive oxygen species (ROS) inhibitor N‑acetylcysteine, as well as lipid peroxidation inhibitors Liproxstatin‑1 and iron chelator deferoxamine; however, inhibitors of apoptosis, necrosis or autophagy had no effect. It was also demonstrated that iron and lipid ROS levels were elevated in I/R injury and that mitochondria decreased in size and increased in membrane density, which is indicative of ferroptosis. Furthermore, the generation of lipid ROS suggests iron accumulation and glutathione (GSH) depletion. The expression of ferroportin (Fpn) protein and mRNA was decreased in TM4 cells. Notably, overexpression of Fpn inhibited ferroptosis, lipid ROS generation and iron accumulation. In addition, GSH‑dependent peroxidase 4 (GPX4) was inactivated via GSH depletion following I/R injury, whereas GPX4 activation blocked I/R‑induced ferroptosis by reducing lipid ROS levels. The mitogen‑activated protein kinase (MAPK) pathway was also investigated in the present study; it was observed that I/R‑induced ferroptosis was blocked by inhibiting p38 MAPK activation. The results of the present study demonstrate that ferroptosis is a pervasive and dynamic type of cell death induced by OGD/R injury in Sertoli cells. This may provide a novel insight into the application of cytoprotection in testicular I/R damage‑induced cell loss.

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Section: Discussionmentioning

confidence: 99%

Ferroptosis is associated with oxygen-glucose deprivation/reoxygenation-induced Sertoli cell death

Zhao

et al. 2018

Int J Mol Med

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“…In another study, Chen et al. demonstrated that oral administration of pentoxifylline prevented pathological damage to the testes by suppressing oxidative stress [ 29 ]. Also, Yao et al.…”

Section: Introductionmentioning

confidence: 99%

“…Also, Yao et al. (2016) showed that PTX prevented against intermittent hypobaric hypoxia induced-oxidative stress in testicular tissue by maintaining redox homeostasis [ 29 ]. Furthermore, Salahshoor et al reported that pentoxifylline protected rats against Dimethyl nitrosamine (DMN) induced testicular damage and improved sperm motility and viability [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

Pentoxifylline improves the survival of spermatogenic cells via oxidative stress suppression and upregulation of PI3K/AKT pathway in mouse model of testicular torsion-detorsion

Dhulqarnain

Takzaree

Hassanzadeh

et al. 2021

Heliyon

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Testicular torsion-detorsion results in enhanced formation of free radicals which contribute to the pathophysiology of testicular tissue damage. Recent reports have identified protective role of pentoxifylline (PTX) against free radicals. Thus, we determined the protective effect of pentoxifylline against testicular damage in mouse model of testicular torsion-detorsion. Twenty (6 weeks old) male mice were divided into 4 groups of 5 animals each namely: Control (sham operated group), T1 (Torsion-detosion + single dose 100 mg/kg PTX, T2 (torsion-detorsion + 20 mg/kg PTX for 2 weeks and T/D (torsion-detorsion only). Animals in T1, T2 and T/D groups underwent 2 h of testicular torsion with the left testes rotated 720° (clockwisely) followed by 30 min of detorsion. After detorsion, drug administration was done intraperitoneally. The left testes of all the animals were excised on the 35th day after torsion-detortion for histopathological and biochemical assay. Histomorphological analysis of the seminiferous tubules showed that there were significant increase (P < 0.01 or 0.05) in the mean seminiferous tubule diameter, Johnson score and germ cells of animals in Control and T1 compared to T2 and T/D with no significant difference (P > 0.05) in testes weight, sertoli, leydig and myoid cells in all groups. IHC results showed significant increase (P < 0.01 or 0.05) in id4 and scp3 protein markers in Control, T1 and T2 compared to T/D. Oxidative stress analysis revealed that Pentoxifylline significantly increased (P < 0.01 or 0.05) the level of SOD, catalase, mRNA expression of akt and pi3k genes but significantly suppress (P < 0.01 or 0.05) MDA and Caspase-3 level in Control, T1 and T2 compared to T/D. Pentoxifylline could be used as an adjunct therapy to surgery in the treatment of torsion-detorsion related testicular injury, However, Further studies are needed to evaluate the effects of pentoxifylline on testicular torsion.

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“…Recent evidence showed that PTX inhibits ROS generation and improves capillary circulation and tissue oxygenation in various organs. For instance, Yao et al (2016) showed that PTX could prevent intermittent hypobaric hypoxia induced-oxidative stress in testicular tissue by maintaining redox homeostasis [ 17 ]. Zhang et al (2005) reported that PTX might be beneficial in reducing hydrogen peroxide induced embryo injury and improve in vitro fertilization (IVF) outcome [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Pentoxifylline Attenuates Arsenic Trioxide‐Induced Cardiac Oxidative Damage in Mice

Gholami

Ataei

Ahmadimoghaddam

et al. 2021

Oxidative Medicine and Cellular Longevity

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This study was undertaken to evaluate the therapeutic potential effect of pentoxifylline (PTX) against arsenic trioxide (ATO)-induced cardiac oxidative damage in mice. Thirty-six male albino mice were divided into six groups and treated intraperitoneally with normal saline (group 1), ATO (5 mg/kg; group 2), PTX (100 mg/kg; group 3), and different doses of PTX (25, 50, and 100 mg/kg; groups 4, 5, and 6, respectively) with ATO. After four weeks, the blood sample was collected for biochemical experiments. In addition, cardiac tissue was removed for assessment of oxidative stress markers and histopathological changes (such as hemorrhage, necrosis, infiltration of inflammatory cells, and myocardial degeneration). The findings showed that ATO caused a significant raise in serum biochemical markers such as lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and troponin-I (cTnI), glucose, total cholesterol (TC), and triglyceride (TG) levels. In addition to histopathological changes in cardiac tissue, ATO led to the significant increase in cardiac lipid peroxidation (LPO) and nitric oxide (NO); remarkable decrease in the activity of cardiac antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx); and the depletion of the total antioxidant capacity (TAC) and total thiol groups (TTGs). PTX was able to reduce the increased levels of serum cardiac markers (LDH, CPK, cTnI, TC, and TG), cardiac LPO, and improve antioxidant markers (TAC, TTGs, CAT, SOD, and GPx) alongside histopathologic changes. However, no significant changes were observed in elevated serum glucose and cardiac NO levels. In conclusion, the current study showed the potential therapeutic effect of PTX in the prevention of ATO-induced cardiotoxicity via reversing the oxidative stress.

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Protection of Pentoxifylline against Testis Injury Induced by Intermittent Hypobaric Hypoxia

Cited by 22 publications

References 47 publications

Ferroptosis is associated with oxygen-glucose deprivation/reoxygenation-induced Sertoli cell death

Ferroptosis is associated with oxygen-glucose deprivation/reoxygenation-induced Sertoli cell death

Pentoxifylline improves the survival of spermatogenic cells via oxidative stress suppression and upregulation of PI3K/AKT pathway in mouse model of testicular torsion-detorsion

Pentoxifylline Attenuates Arsenic Trioxide‐Induced Cardiac Oxidative Damage in Mice

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