Testicular Oxidative Damage Research Articles

PTD-FNK Alleviated LPS-Induced Oxidative Stress of Boar Testicular Sertoli Cells via Keap1-Nrf2 Pathway

PTD-FNK, a synthetic anti-apoptotic protein, has been shown to potently alleviate cellular injuries. However, the effects of PTD-FNK on oxidative defense in boar testicular Sertoli cells (SCs) against oxidative injury has not been explored. In this study, we show that exposure of SCs to 100 mg/L lipopolysaccharide (LPS) for 12 h leads to decreased survival rate, superoxide dismutase (SOD) activity, and increased malondialdehyde (MDA). Treatment with 0.01 nmol/L PTD-FNK for 4 h significantly enhanced the activity of SOD, catalase (CAT), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) in SCs. Concurrently, PTD-FNK treatment effectively reduced the production of reactive oxygen species (ROS) and the levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) in SCs. Moreover, using His pull-down and LC-MS techniques, we identified PTD-FNK-interacting proteins and confirmed that this protective effect may be mediated by the regulation of the Keap1-Nrf2 signaling pathway by PTD-FNK. Therefore, PTD-FNK alleviates LPS-induced oxidative stress via the Keap1/Nrf2 pathway, providing novel insights for the development of therapeutic agents targeting testicular oxidative damage.

Testicular oxidative DNA damage induced by cyclophosphamide and the impact role of pumpkin seed extract: Descriptive histopathological, ultrastructural, and immunohistochemical analysis

Testicular oxidative DNA damage induced by cyclophosphamide and the impact role of pumpkin seed extract: Descriptive histopathological, ultrastructural, and immunohistochemical analysis

Protective Effects of Syringic Acid Against Oxidative Damage, Apoptosis, Autophagy, Inflammation, Testicular Histopathologic Disorders, and Impaired Sperm Quality in the Testicular Tissue of Rats Induced by Mercuric Chloride.

Mercury (Hg) is one of the most toxic heavy metals that damage testicular tissue. Mercury chloride (HgCl2) is one of the most toxic forms of mercury that can easily cross biological membranes. Syringic acid (SA) is a natural flavonoid found in many vegetables and fruits. In this study, the effects of SA against HgCl2-induced testicular damage in rats were determined by biochemical, histopathological, and spermatological analyses. For this study, a total of 35 Spraque Dawley rats were used. Rats were divided into five groups as control, HgCl2, SA 50, HgCl2 + SA 25, and HgCl2 + SA 50. HgCl2 was administered intraperitoneal (IP) at a dose of 1.23 mg/kg/bw, while SA was administered by oral gavage at doses of 25 and 50 mg/kg/bw. The rats were then sacrificed, and testicular tissues were removed. HgCl2 caused an increase in MDA level and a decrease in SOD, CAT, and GPx activity and GSH level in the testicular tissue of rats. HgCl2 is involved in the increase of eIF2-α, PERK, ATF-4, ATF-6, CHOP, NF-κB, TNF-α, IL-1β, Apaf-1, Bax, and Caspase-3 mRNA expression. HgCl2 caused a decrease in sperm motility, an increase in the rate of abnormal sperm and sperm DNA fragmentation in rats. However, SA oral administration dose-dependently inhibited endoplasmic reticulum stress, oxidative stress, inflammation, and apoptosis and preserved epididymal sperm quality and testicular histoarchitectures. In conclusion, SA had protective effects against HgCl2-induced testicular oxidative damage, inflammation, endoplasmic reticulum stress, and apoptosis.

Ameliorative effects of sinapic acid against vancomycin-induced testicular oxidative damage, apoptosis, inflammation, testicular histopathologic disorders and decreased epididymal sperm quality

In this study, it was aimed to determine the effect of sinapic acid (SNP), a polyphenol with antioxidant, anti-inflammatory and antibacterial properties, on testicular damage caused by vancomycin (VCM), a widely used antibiotic against gram positive bacteria. A total of 35 male Sprague Dawley rats were used in the study, divided into five groups: control, VCM, SNP, VCM + SNP 10, and VCM + SNP 20. Following a week of oral administration, the rats were euthanized under sevoflurane anesthesia. While the VCM group had a significant increase in MDA levels, the SNP administration inhibited the increase in MDA levels. VCM led to a significant decrease in GSH levels, SOD, CAT, and GPx activity in the testicular tissue of rats, while SNP administration increased these antioxidant levels. SNP administration decreased the mRNA expression levels of VCM induced Nrf-2, HO-1, and NQO1 in testicular tissue while increasing the levels of MAPK14, MAPK15, JNK, P53, Apaf-1, Caspase-3, Caspase-6, Caspase-9, and Beclin-1 mRNA transcript levels. The VCM group showed a significant increase in Bax and NF-κB levels in testicular tissue, while Bcl-2 levels decreased. VCM significantly decreased sperm motility and increased the percentage of damaged sperm in rats. Histopathological results revealed that VCM caused disruption of basement membranes and disorganization of seminiferous tubules, but SNP administration preserved testicular histology. As a result, VCM increased oxidative stress, apoptosis, and autophagy in the testicular tissue of rats, altered testicular histopathology, and decreased sperm quality, while SNP decreased these effects.

Effects of empagliflozin on gonadal functions of hyperglycemic male wistar rats.

Empagliflozin (EMPA) showed antiapoptotic, oxidative and anti-inflammatory potential effect. EMPA attenuates the inflammation and oxidative stress biomarkers in patients with heart failure while significantly decreases the malondialdehyde (a lipid peroxidation marker) levels in the plasma of diabetic patients. The present study examined the effects of moderate hyperglycemia on reproductive function. Sixty male Wister rats ‎ were divided and randomly allocated into four groups of 15 animals each‎‎. Diabetes was induced by a single intraperitoneal injection of a prepared solution containing STZ diluted in 0.1 M sodium citrate buffer (pH 4.5) at a dosage of 40 mg/kg body weight in selected in groups II and III for seven days before starting the treatment with EMPA. The current study revealed that EMPA for eight weeks prevented testicular high glucose-induced oxidative stress markers such as penile nitric oxide (NO), glutathione peroxidase (GPX) and total anti-oxidant capacity (TAC) in STZ-induced hyperglycemia in a rat model. In addition, EMPA ameliorated the high levels of endogenous Interleukin-6 (IL-6) present in gonads in response to an acute inflammatory found in the hyperglycemic STZ-induced rats. The present study further suggested the protective effects of EMPA and how it has a beneficial role and can effectively attenuate hyperglycemia-induced testicular oxidative damage and inflammatory markers as well as androgen dependent testicular enzymes activity as a protective role against the consequences of hyperglycemia and male sub-infertility.

3-(4-methoxyphenyl) acrylic acid halts redox imbalance and modulate purinergic enzyme activity in iron-induced testicular injury

Abstract Various derivatives of cinnamic acid have been reported to possess significant activities such as antioxidant and hepatoprotective, and neuroprotective activities. Interestingly, testicular toxicity has been linked to several causes, with oxidative damage being one of the pathophysiological mechanisms. 3-(4-methoxyphenyl) acrylic acid (1), a derivative of cinnamic acid, was synthesized and then investigated for its effects on iron-induced testicular injury and oxidative stress via ex vivo and in silico studies, respectively. Evaluations were done on KAD-1’s FRAP, DPPH free radical scavenging activity, and iron chelating potential. Through the ex vivo incubation of tissue supernatant and 0.1 mM FeSO4 for 30 min at 37 °C with different concentration of 1, oxidative testicular damage treatments were induced. The scavenging property of 1 increases significantly (p < 0.05) as the concentration increases when compared with the standard quercetin. The MDA, CAT, ATPase, and ENTPDase activities were reduced when testicular damage was induced (p < 0.05). The group treated with 30 mg/mL had the highest level of MDA. A significant rise in GSH level and activity of SOD were observed. The result obtained indicated that 1 has the potential to prevent oxidative testicular toxicity, as evidenced by its capacity to control nucleotide hydrolysis and reduce oxidative stress. Overall, the results of this experimental study point to some possible uses of 3-(4-methoxyphenyl) acrylic acid (1) in the prevention of oxidative testicular dysfunction. Therefore, 3-(4-methoxyphenyl) acrylic acid (1) would be a good product in developing a medication to alleviate male infertility.

Chlorocholine chloride exposure induced spermatogenic dysfunction via iron overload caused by AhR/PERK axis-dependent ferritinophagy activation

Chlorocholine chloride (CCC) is a plant growth regulator used worldwide that is detectable in cereals, fruits and animal products. The health effects of CCC exposure have raised public concern. Our previous research showed that CCC exposure decreased testosterone synthesis in pubertal rats. However, little is known about whether and how pubertal CCC exposure impacts spermatogenesis. In this study, we used BALB/c mice and spermatogonia-derived GC-1 cells to examine CCC-induced spermatogenic dysfunction. In vivo, pubertal CCC exposure led to decreased testicular weight, decreased testicular germ cells and poor sperm quality. This effect worsened after cessation of CCC exposure for the next 30 days. RNA-seq and western blot analysis revealed that CCC induced aryl hydrocarbon receptor (AhR) signaling, endoplasmic reticulum stress (ERS) and ferritinophagy. Increased iron content and lipid peroxidation levels were also observed in CCC-treated testes. In vitro, it was identified that iron overload mediated by enhanced ferritinophagy occurred in CCC-treated GC-1 cells, which might be attributed to the PERK pathway in ERS. Further, for the first time, our study elucidated the involvement of AhR in CCC-induced iron overload, which aggravated testicular oxidative damage via lipid peroxidation. Considering the adverse impact of CCC exposure on rodents, supportive evidence from GC-1 cells, and the critical importance of spermatogenesis on male development, the effects of CCC on the male reproduction warrant increased attention.

Melatonin alleviates oxidative stress damage in mouse testes induced by bisphenol A.

We investigated the effect of melatonin on bisphenol A (BPA)-induced oxidative stress damage in testicular tissue and Leydig cells. Mice were gavaged with 50mg/kg BPA for 30days, and concurrently, were injected with melatonin (10mg/kg and 20mg/kg). Leydig cells were treated with 10μmol/L of BPA and melatonin. The morphology and organ index of the testis and epididymis were observed and calculated. The sperm viability and density were determined. The expressions of melatonin receptor 1A and luteinizing hormone receptor, and the levels of malonaldehyde, antioxidant enzymes, glutathione, steroid hormone synthases, aromatase, luteinizing hormone, testosterone, and estradiol were measured. TUNEL assay was utilized to detect testicular cell apoptosis. The administration of melatonin at 20mg/kg significantly improved the testicular index and epididymis index in mice treated with BPA. Additionally, melatonin promoted the development of seminiferous tubules in the testes. Furthermore, the treatment with 20mg/kg melatonin significantly increased sperm viability and sperm density in mice, while also promoting the expressions of melatonin receptor 1A and luteinizing hormone receptor in Leydig cells of BPA-treated mice. Significantly, melatonin reduced the level of malonaldehyde in testicular tissue and increased the expression of antioxidant enzymes (superoxide dismutase 1, superoxide dismutase 2, and catalase) as well as the content of glutathione. Moreover, melatonin also reduced the number of apoptotic Leydig cells and spermatogonia, aromatase expression, and estradiol level, while increasing the expression of steroid hormone synthases (steroidogenic acute regulatory protein, cytochrome P450 family 17a1, cytochrome P450 17α-hydroxylase/20-lyase, and, 17β-hydroxysteroid dehydrogenase) and the level of testosterone. Melatonin exhibited significant potential in alleviating testicular oxidative stress damage caused by BPA. These beneficial effects may be attributed to melatonin's ability to enhance the antioxidant capacity of testicular tissue, promote testosterone synthesis, and reduce testicular cell apoptosis.

Ameliorative effects of rutin and rutin-loaded chitosan nanoparticles on testicular oxidative stress and histological damage induced by cyclophosphamide in male rats

Cyclophosphamide (CP) is broadly used to kill various tumor cells; however, its repeated uses have been reported to cause reproductive dysfunction and infertility. Natural flavonoid, rutin (RUT), possesses strong antioxidant and antiapoptotic activity that is attributed to ameliorate the reproductive dysfunction induced by CP. Many previous studies proved that the formulation of flavonoids in nanoemulsion has a promising perspective in mitigating the side effects of chemotherapy. Therefore, the main objective of this study was to investigate the ameliorative effects of RUT and RUT-loaded chitosan nanoparticles (RUT-CH NPs) against CP-induced reproductive dysfunction in male rats. For this aim, thirty-six male albino rats were randomly allocated into six groups as follows: control, RUT, RUT-CH NPs, CP, CP + RUT, and CP + RUT-CH NPs. In the CP groups, a single intraperitoneal injection of CP (150 mg/kg bwt) was administered on the first day of the experiment. RUT and RUT-CH NPs were orally administered either alone or with CP injection at a dose of 10 mg/kg bwt per day for 60 days. The results revealed that CP administration caused significant testicular oxidative stress damage through increasing the nitric oxide and malondialdehyde levels as well as decreasing the total antioxidant capacity and reduced glutathione contents. It also impaired spermatogenesis and steroidogenesis via altering the transcription levels of CYP11A1, HSD-3b, StAR, Bax, bcl-2, and Nrf-2 genes. Otherwise, the oral intake of either RUT or RUT-CH NPs with CP injection effectively attenuated these alterations and significantly improved the microscopic appearance of testicular tissue. In conclusion, this study highlights the potential of RUT either free or NPs in mitigating CP-induced testicular dysfunction via its antioxidant and anti-apoptotic properties.

Diosmin protects the testicles from doxorubicin-induced damage by increasing steroidogenesis and suppressing oxido-inflammation and apoptotic mediators.

Cancer chemotherapy with doxorubicin (DOX) has been linked to serious testicular damage and spermatotoxicity due to the induction of oxidative stress, inflammation, and apoptosis. Thus, the current study was carried out to assess the potential ameliorative impact of diosmin, an antioxidant drug, against DOX-mediated spermatoxicity and testicular injury in rats. In the experimental protocol, rats were grouped into 4: Group 1 received vehicle and saline for 8 weeks while group 2 received diosmin and saline concomitantly for 8 weeks. Group 3 was given 3 mg/kg intraperitoneal DOX once every 7 days for 8 weeks. Group 4 was given 40 mg/kg of diosmin orally for 56 days followed by DOX diosmin administration after one hour. After 56 days of treatment, sperm quality, hormonal testing, biochemical parameters, and histological alterations in the testes were evaluated. DOX-induced reduce spermatogenic function, testicular 3- and 17β-Hydroxysteroid dehydrogenases, and serum follicle stimulating hormone, luteinizing hormone, and testosterone. It also enhanced inflammation, testicular oxidative damage, and apoptosis. The histopathologic examinations corroborated the biochemical results obtained. Significantly, diosmin treatment reduced DOX-induced injury, as evidenced by restored testicular architecture, increased steroidogenesis, preservation of spermatogenesis, suppression of oxide-inflammatory response, and apoptosis. It was found that through diosmin antioxidant, anti-apoptotic, and anti-oxido-inflammatory it presents a possible therapeutic alternative for protecting testicular tissue against DOX's harmful effects.

Effect of Spirulina maxima microcapsules to mitigate testicular toxicity induced by cadmium in rats: Optimization of in vitro release behavior in the milk beverage

The research investigates the effects of freeze-dried Spirulina maxima microcapsules in reducing testicular toxicity in rats and optimizing the in vitro release behavior of milk beverages using response surface methodology (RSM). Particle size, polydispersity index and zeta-potential were impacting microcapsules’ stability and bioactivity. Thirty-six male Sprague-Dawley rats were utilized; eighteen of them received cadmium orally at a dose of 0.5 mg/mL/rat/d. The nutritional and biochemical parameters were evaluated. Non-encapsulated and Spirulina maxima microcapsules exhibited no significant adverse consequences in vitro experiment. Spirulina maxima microcapsules defended rats against both the inflammatory and apoptotic consequences triggered by cadmium. Incorporating Spirulina maxima microcapsules into the milk beverage at 3 % optimized in vitro release behavior of antioxidants and phenolics due to the increasing importance of these compounds' biological activity. Spirulina maxima microcapsules guide as a viable approach for providing nutritional enrichment in the food industry; moreover, protecting against cadmium-induced oxidative testicular damage in rats.

Cytoprotective potency of naringin against di-n-butylphthalate (DBP)-induced oxidative testicular damage in male rats

The present study aimed to investigate the protective potential of naringin (NG) against di-n-butyl phthalate (DBP)- induced testicular damage and impairment of spermatogenesis in rats. Forty-two male Wistar albino rats were divided into six equal groups, and treated orally, 3 times weekly for 8 successive weeks. Control vehicle group was administrated olive oil, naringin-treated group was administered NG (80 mg/kg), DBP 250- and DBP 500- intoxicated groups received DBP (250 mg/kg) and (500 mg/kg), respectively, NG + DBP 250 and NG + DBP 500 groups received NG, an hour prior to DBP 250 and 500 administration. The results revealed that DBP induced dose-dependent male reproductive dysfunctions, included a significant decrease in the serum testosterone level concomitantly with significant decreases in the sperm count, viability, and total motility. Meanwhile, DBP significantly increased the testicular malondialdehyde level with significant reductions of glutathione content and catalase activity. Histopathologically, DBP provoked absence of spermatozoa, degenerative changes in the cell layers of seminiferous tubules and a significant decrease in the thickness of the seminiferous tubules epithelium. Conversely, the concomitant treatment with NG, one hour before DBP 250 or 500- intoxication mitigated the dose-dependent reproductive dysfunctions induced by DBP, evidenced by significant increases of serum testosterone level, sperm motility, count and viability along with marked improvement of the oxidant/antioxidant status and testicular histoarchitecture. In conclusion, the findings recorded herein proved that NG could mitigate DBP-induced testicular damage and impairment of spermatogenesis, suggesting the perspective of using NG as a natural protective and therapeutic agent for alleviating the reproductive dysfunctions and improving reproductive performance, mainly via its potent antioxidant activity.

Garden Cress Seed Oil Abrogates Testicular Oxidative Injury and NF-kB-Mediated Inflammation in Diabetic Mice.

Diabetes mellitus is a metabolic disorder associated with various complications encompassing male reproductive dysfunction. The present study aimed to investigate the therapeutic potential of biologically active Lepidium sativum seed oil (LSO) against the testicular dysfunction associated with streptozotocin (STZ)-induced diabetes. Male adults (n = 24) were divided into four groups: control, LSO-administered, diabetic (D), and LSO-treated diabetic (D+LSO) groups. LSO was extracted from L. sativum seeds, and its chemical composition was determined using GC-MS. Serum testosterone levels, testicular enzymatic antioxidants (catalase (CAT) and superoxide dismutase (SOD)), an oxidative stress (OS) biomarker, malondialdehyde (MDA), pro-inflammatory markers (NF-kB, IL-1, IL-6, and TNF-α), and the expression level of NF-kB were assessed. In addition, histopathological changes were evaluated in testicular tissues. The results obtained showed that the chemical composition of LSO indicated its enrichment mainly with γ-tocopherol (62.1%), followed by 2-methylhexacosane (8.12%), butylated hydroxytoluene (8.04%), 10-Methylnonadecane (4.81%), and δ-tocopherol (3.91%). Moreover, LSO administration in the D+LSO mice significantly increased testosterone levels and ameliorated the observed testicular oxidative damage, inflammatory response, and reduced NF-kB expression compared to the diabetic mice. Biochemical and molecular analyses confirmed the histological results. In conclusion, LSO may prevent the progression of diabetes-induced impairment in the testes through inhibition of the OS- and NF-kB-mediated inflammatory response.

Melatonin or vitamin C attenuates lead acetate-induced testicular oxidative and inflammatory damage in mice by inhibiting oxidative stress mediated NF-κB signaling

Lead (Pb) acts as an environmental endocrine disruptor and has negative effects in animals; excessive accumulation of lead causes reproductive dysfunction in male animals. Oxidative stress plays a vital role in Pb-induced injury. However, the mechanisms underlying chronic testicular toxicity of Pb remain unclear. In this study, we aimed to determine the effects of lead acetate on reproductive function in male mice, identify the underlying mechanisms, and test counter measures to alleviate the toxic effects. Male mice were dosed with lead acetate (500 mg/L) in free drinking water for 12 weeks, and administered melatonin (5 mg/kg) or vitamin C (500 mg/kg) by intraperitoneal injection. Blood from the eyeball, testicles, and sperm from the caudal epididymis were collected after 12 weeks and analyzed. Pb exposure reduced sperm count and motility, increased sperm malformation (P < 0.01), disrupted testicular morphology and structure, and decreased the expression of steroid hormone synthesis-related enzymes and serum testosterone concentration (P < 0.01). Pb also increased the number of inflammatory cells and the levels of the pro-inflammatory cytokines TNF-α and IL-6 (P < 0.01), and activated NF-κB signaling. Furthermore, the ROS yield and oxidation indicators LPO and MDA were significantly increased (P < 0.01), and the antioxidant indicators T-AOC, SOD, and GSH were significantly reduced (P < 0.01). Treatment with melatonin or vitamin C reversed the effects of lead acetate; vitamin C was more effective in restoring SOD activity (P < 0.01) and enhancing ZO-1 protein levels (P < 0.01). Thus, long-term exposure to lead acetate at low concentrations could adversely affect sperm quality and induce inflammatory damage by oxidative stress mediated NF-κB signaling. Vitamin C could act as a protective agent and improve reproductive dysfunction in male animals after lead accumulation.

In vivo exposure to bisphenol F induces oxidative testicular toxicity: role of Erβ and p53/Bcl-2 signaling pathway.

Bisphenol F (BPF), an alternative to bisphenol A has been implicated as a gonadotoxic substance. BPF has been shown to induce hormonal imbalance and testicular oxidative damage. However, the mechanism associated with BPF-induced testicular toxicity has not been fully explored. This study was designed to explore the role of tumor protein (p53)/ B-cell lymphoma 2 (BCl-2) signaling and oestrogen receptor beta (Erβ) in BPF-induced testicular toxicity. Male Wistar rats were randomized into control (Cntrl), BPF-treated (10, 30, and 50 mg/kg for low dose (BPF-L), medium dose (BPF-M), and high dose (BPF-H) respectively), and BPF-treated recovery (Cntrl-R, BPF-L-R, BPF-M-R, and BPF-H-R). The administration was via gavage and lasted for 28 days and the animals in the recovery groups were allowed 28-days exposure free period for recovery from BPF exposure. BPF resulted in the distortion of the testicular histoarchitecture, which was accompanied by a significant rise in testicular gamma-lutamyl transferase and lactate dehydrogenase activities but a decline in sorbitol dehydrogenase activities. Also, BPF caused a significant reduction in plasma gonadotropin-releasing hormone, luteinising hormone, follicle-stimulating hormone, and testosterone, which was associated with the downregulation of testicular 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase activities. Furthermore, BPF induced testicular inflammation, redox imbalance, and apoptosis, accompanied by distortion in p53/BCl-2 signaling and overexpression of Erβ. Again, the observed toxic effects of BPF were dose-dependent and not completely reversed by BPF cessation. Bisphenol F induced gonadotoxicity by distorting p53/BCl2 signaling and the expression of Erβ. These observed alterations were not completely reversed after the cessation of BPF exposure.

Antioxidant Nanoparticles Restore Cisplatin-Induced Male Fertility Defects by Promoting MDC1-53bp1-Associated Non-Homologous DNA Repair Mechanism and Sperm Intracellular Calcium Influx.

Cisplatin, a commonly used anticancer compound, exhibits severe off-target organ toxicity. Due to its wide application in cancer treatment, the reduction of its damage to normal tissue is an imminent clinical need. Cisplatin-induced testicular oxidative stress and damage lead to male sub- or infertility. Despite earlier studies showing that the natural polyphenol extracts honokiol serve as the free radical scavenger that reduces the accumulation of intracellular free radicals, whether honokiol exhibits direct effects on the testis and sperm is unclear. Thus, the aim of the current study is to investigate the direct effects of honokiol on testicular recovery and sperm physiology. We encapsulated this polyphenol antioxidation compound into liposome-based nanoparticles (nHNK) and gave intraperitoneally to mice at a dosage of 5 mg/kg body mass every other day for consecutive 6 weeks. We showed that nHNK promotes MDC1-53bp1-associated non-homologous DNA double-strand break repair signaling pathway that minimizes cisplatin-induced DNA damage. This positive effect restores spermatogenesis and allows the restructuring of the multi-spermatogenic layers in the testis. By reducing mitochondrial oxidative damage, nHNK also protects sperm mitochondrial structure and maintains both testicular and sperm ATP production. By a yet-to-identify mechanism, nHNK restores sperm calcium influx at the sperm midpiece and tail, which is essential for sperm hypermotility and their interaction with the oocyte. Taken together, the nanoparticulated antioxidant counteracts cisplatin-induced male fertility defects and benefits patients undertaking cisplatin-based chemotherapy. These data may allow the reintroduction of cisplatin for systemic applications in patients at clinics with reduced testicular toxicity.

Protective Effects of Syringic Acid on Ischemia-Reperfusion Injury in Testicular Torsion: An Experimental Study in a Rat Model.

The purpose of this study was to assess the effectiveness of syringic acid in preventing ischemia-reperfusion injury following detorsion in a rat model of induced testicular torsion. In our study, a total of 24 rats, eight in each group, were used. Group 1 served as the control group. Group 2 underwent testicular torsion and detorsion. Group 3 underwent the same procedures as Group 2, but also received 100 mg/kg syringic acid immediately following ischemia. Spectrophotometric analysis was performed on blood samples, and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as the values of malondialdehyde (MDA), were evaluated under direct microscopic examination of the testis to determine tissue injury. The architecture of the seminiferous tubules and spermatogenesis processes were graded using the Johnsen and Cosentino scoring systems. The mean value of MDA was higher in Group 2 compared to the other groups (p < 0.001). Group 3 demonstrated a decline in the concentrations of proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta, as indicated by biochemical analysis of blood samples, when compared to Group 2 (p-values: 0.045, 0.001, and <0.001, respectively). In addition, the improvement in Johnsen and Cosentino scores was significantly higher in Group 3 compared to Group 2 (p = 0.028 and p = 0.001, respectively). These findings suggest that syringic acid has a protective effect against testicular oxidative damage.

The Effect of Carvacrol Plus Treadmill Exercise on Testis Structure and Oxidative Stress in Streptozotocin-Induced Diabetic Rats

Objectives: This study aimed to evaluate the effect of carvacrol and treadmill exercise on oxidative stress and testis structure in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: In this experimental study, the diabetes was induced using a single intraperitoneal (IP) injection of STZ (50 mg/kg). The rats were assigned to five groups, namely a control group, a diabetic control group, a diabetic group receiving daily carvacrol at a dose of 75 mg/kg, diabetic groups performing treadmill exercise, and a diabetic group performing daily treadmill exercise and receiving carvacrol. After covering the treatment period, all rats were anesthetized and their blood sample were taken. Then the serum levels of oxidative stress markers were measured, the testicles and epididymis were removed, and the sperm parameters were assessed. Results: The treatment of diabetic rats with carvacrol and treadmill exercise effectively improved testis tissue damage, sperm parameters, glucose, and insulin plasma levels (P=0.001). In diabetic rats, the level of malondialdehyde (MDA) increased while the activity of superoxide dismutase (SOD) and catalase (CAT) enzymes decreased in the testes tissue (P=0.001). However, when carvacrol administration (75 mg/kg) was combined with treadmill exercise, these parameters were significantly rectified (P&lt;0.05). Conclusion: In sum, administering carvacrol and performing treadmill exercise were effective in improving the sperm parameters and testicular oxidative damage caused by diabetes.

Fenofibrate and Diosmetin in a rat model of testicular toxicity: New insight on their protective mechanism through PPAR-α/NRF-2/HO-1 signaling pathway

One of the most significant chemotherapeutic side effects of cisplatin (Cis) that limits its use and efficacy is testicular toxicity. Thus, the objective of the present study was to investigate the possible ameliorative effect of Fenofibrate (Fen), Diosmetin (D), and their combination against cis-mediated testicular damage. Fifty-four adult male albino rats were randomly allocated into nine groups (6 rats each): Control group, Fen (100 mg/kg), D20 (20 mg/kg), D40 (40 mg/kg), Cis group (7 mg/kg), Cis +Fen group (7 mg/kg+100 mg/kg), Cis+D20 group (7 mg/kg+20 mg/kg), Cis+D40 group (7 mg/kg+40 mg/kg), Cis+Fen+D40 treated group (7 mg/kg+100 mg/kg+40 mg/kg). Relative testicular weight, epididymal sperm count and viability, serum testosterone level, testicular oxidative stress indices, mRNA expression of peroxisome proliferator-activated receptor alpha (PPAR-α), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), histopathological, and immunohistochemical alterations were assessed. Our results revealed that cis administration induced testicular oxidative and inflammatory damage as indicated by a substantial reduction in relative testicular weight, sperm parameters, serum testosterone levels, the antioxidant enzyme activity of catalase, and Johnson's histopathological score, PPAR-α/NRF-2/HO-1 and proliferating cell nuclear antigen (PCNA) immunoexpression with marked increment in malondialdehyde (MDA), Cosentino's score, nuclear factor kappa B (NF-κβ p65), interleukin (IL)− 1β and caspase 3 in testicular tissue. Interestingly, Fen and D diminished the harmful effects of cis on testes via upregulation of the antioxidant activities and downregulation of lipid peroxidation, apoptosis, and inflammation. Moreover, the combination therapy Fen/D40 also exhibited a more pronounced enhancement of previous markers than either treatment alone. In conclusion, because of their antioxidant, anti-inflammatory, and anti-apoptotic properties, cotreatment with Fen or D or their combination could be beneficial in reducing the harmful impacts of cis on testicular tissue, particularly in patients that receive cis chemotherapy.

Beet leaf (beta vulgaris L.) extract attenuates iron-induced testicular toxicity: Experimental and computational approach

The purpose of this study was to investigate the protective effect of Beta vulgaris leaf extract (BVLE) on Fe2+-induced oxidative testicular damage via experimental and computational models. Oxidative testicular damage was induced via incubation of testicular tissue supernatant with 0.1 mM FeSO4 for 30 min at 37 °C. Treatment was achieved by incubating the testicular tissues with BVLE under the same conditions. The catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) levels, acetylcholinesterase (AChE), sodium-potassium adenosine triphosphatase (Na+/K + ATPase), ecto-nucleoside triphosphate diphosphohydrolase (ENTPDase), glucose-6-phosphatase (G6Pase), and fructose-1,6-bisphosphatase (F-1,6-BPase) were all measured in the tissues. We identified the bioactive compounds present using high-performance liquid chromatography (HPLC). Molecular docking and dynamic simulations were done on all identified compounds using a computational approach. The induction of testicular damage (p < 0.05) decreased the activities of GSH, SOD, CAT, and ENTPDase. In contrast, induction of testicular damage also resulted in a significant increase in MDA and NO levels and an increase in ATPase, G6Pase, and F-1,6-BPase activities. BVLE treatment (p < 0.05) reduced these levels and activities compared to control levels. An HPLC investigation revealed fifteen compounds in BVLE, with quercetin being the most abundant. The molecular docking and MDS analysis of the present study suggest that schaftoside may be an effective allosteric inhibitor of fructose 1,6-bisphosphatase based on the interacting residues and the subsequent effect on the dynamic loop conformation. These findings indicate that B. vulgaris can protect against Fe2+-induced testicular injury by suppressing oxidative stress, acetylcholinesterase, and purinergic activities while regulating carbohydrate dysmetabolism.