Tadalafil alleviates cisplatin-induced reproductive toxicity through the activation of the Nrf2/HO-1 pathway and the inhibition of oxidative stress and apoptosis in male rats

Depression and anxiety are recognized as public health problems. Epidemiological studies have shown that depression and anxiety often occur during reproductive ages between 20 and 60 years of age in males. Trazodone is one of the most frequently prescribed drugs in the treatment of depression and anxiety. Drugs used in repeated doses also play a role in the etiology of infertility. In our study, it was aimed to identify the possible toxic effects of trazodone on male rats and elucidate the underlying mechanisms. Vehicle or trazodone (5, 10, and 20 mg/kg/day) was administered to rats for 28 consecutive days (n=8 per group). At the end of that period, sperm concentration, motility, morphology, and DNA damage were determined and testicular morphology was assessed histopathologically in rats. Additionally, we investigated hormonal status by determining serum testosterone, FSH, and LH levels and oxidative stress by determining glutathione and malondialdehyde levels in testicular tissue to elucidate mechanisms of possible reproductive toxicity. According to our results, sperm concentration, sperm motility, and normal sperm morphology were decreased; sperm DNA damage was increased in trazodone-administered groups. Degenerative findings on the testicular structure were observed after trazodone administration in rats. Additionally, serum FSH, LH, and testosterone levels were elevated in the trazodone-administered groups. Increased MDA levels were the signs of enhanced oxidative stress after trazodone administration in testis tissues. Thus, we concluded that trazodone induced reproductive toxicity in male rats; this reproductive toxicity was accompanied by oxidative stress and hormonal changes, which are considered as important causes of reproductive disorders.

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Melatonin Alleviated Potassium Dichromate-Induced Oxidative Stress and Reprotoxicity in Male Rats

BioMed Research International ◽

10.1155/2021/3565360 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Samir A. E. Bashandy ◽

Hossam Ebaid ◽

Jameel Al-Tamimi ◽

Omar A.-H. Ahmed-Farid ◽

Enayat A. Omara ◽

...

Keyword(s):

Oxidative Stress ◽

Superoxide Dismutase ◽

Sperm Count ◽

Potassium Dichromate ◽

Reproductive Toxicity ◽

Male Rats ◽

Control Group ◽

Necrosis Factor Alpha ◽

Melatonin Administration ◽

Factor Alpha

Melatonin (ML) is a potent antioxidant that reduces oxidative stress. This study was designed to examine the protective effect of melatonin on potassium dichromate- (PDC-) induced male reproductive toxicity. Forty rats were divided into five groups: the control group, rats administered PDC orally (10 mg/kg body weight) for eight weeks, rats administered ML intraperitoneally at doses of either 2.5 or 5 mg/kg followed by the administration of PDC, and rats administered 5 mg/kg ML only. The treatment of rats with PDC led to a decrease in the levels of plasma sex hormones, glutathione, superoxide dismutase, catalase, carnitine, sperm count, and motility. Testicular malondialdehyde levels, nitric oxide concentrations, and abnormalities increased significantly in the PDC group. Melatonin administration to the PDC-treated rats reduced the increase of malondialdehyde and restored the activity of antioxidant enzymes (superoxide dismutase and catalase), glutathione, and sex hormone levels. Moreover, ML attenuated PDC-induced increase in levels of tumor necrosis factor-alpha or interleukin-6. ML alleviated histopathological changes and an increase of p53-positive immune reaction due to PDC. Furthermore, ML inhibited PDC-induced decrease in the DNA content of spermatogenic cells. This study proposed that melatonin may be useful in mitigating oxidative stress-induced testicular damage due to potassium dichromate toxicity.

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Chitosan/Selenium Nanoparticles Attenuate Diclofenac Sodium-Induced Testicular Toxicity in Male Rats

Crystals ◽

10.3390/cryst11121477 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1477

Author(s):

Samy M. El-Megharbel ◽

Fawziah A. Al-Salmi ◽

Sarah Al-Harthi ◽

Khadeejah Alsolami ◽

Reham Z. Hamza

Keyword(s):

Oxidative Stress ◽

Diclofenac Sodium ◽

Chitosan Nanoparticles ◽

Reproductive Toxicity ◽

Male Reproduction ◽

Male Rats ◽

Antioxidant Enzyme Activities ◽

Testicular Function ◽

Wide Range ◽

The Impact

The detrimental effect of diclofenac sodium (Diclo-Na) on male reproductive organs is reported upon in this paper. Chitosan is a polysaccharide composed of various amounts of glucosamine. Chitosan nanoparticles (CH-NPs) have attracted much attention owing to their biomedical activity. Selenium (Se) has a vital role in nutrition, plays an important role in enhancing male reproduction, and has a wide range of free radical scavenging activities. However, the study of the impact of chitosan nanoparticles in combination with Se (IV) (CH-NPs/Se) on male reproductive toxicity associated with Diclo-Na administration is lacking in recent literature. The current study assessed the ameliorative effects of complexes of CH-NPs/Se (IV) on Diclo-Na and the ways in which they alter reproductive toxicity in male rats. Male rats were treated for 30 days successively, either with Diclo-Na (10 mg/kg) or co-treated with a CH-NPs/Se complex (280 mg/kg). Sperm characteristics, marker enzymes of testicular function, LH, FSH, and testosterone were evaluated in addition to oxidative stress markers and histological alterations. CH-NPs/Se significantly alleviated Diclo-Na-induced decline in sperm count and motility, testicular function enzymes, and levels of LH and testosterone in serum. Additionally, CH-NPs/Se co-administration at 280 mg/Kg, inhibited the Diclo-Na-induced decline of antioxidant enzyme activities and elevated oxidative stress indices and reactive free radicals in testicular homogenates of male rats. CH-NPs/Se (280 mg/kg) alone improved Diclo-Na and ameliorated histological damages in exposed rats. In conclusion, chitosan improved testicular function in Diclo-Na-treated rats by enhancing the testosterone hormone levels, ameliorating testicular tissue, and inhibiting markers of oxidative stress in male rats.

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Di(2-ethylhexyl)phthalate induces reproductive toxicity via JAZF1/TR4 pathway and oxidative stress in pubertal male rats

Toxicology and Industrial Health ◽

10.1177/0748233718824911 ◽

2019 ◽

Vol 35 (3) ◽

pp. 228-238 ◽

Cited By ~ 2

Author(s):

Yu-Qin Shi ◽

Guo-Qing Fu ◽

Jing Zhao ◽

Shen-Zhou Cheng ◽

You Li ◽

...

Keyword(s):

Oxidative Stress ◽

Morphological Changes ◽

Reproductive Toxicity ◽

Male Reproduction ◽

Male Rats ◽

Terminal Deoxynucleotidyl Transferase ◽

Cyclin A1 ◽

Ethylhexyl Phthalate ◽

Dehp Exposure ◽

And Oxidative Stress

Di(2-ethylhexyl)phthalate (DEHP) is a typical endocrine-disrupting chemical and reproductive toxicant. Although previous studies have attempted to describe the mechanism by which DEHP exposure results in reproductive dysfunction, few studies focused on puberty, a critical period of reproductive development, and the increased susceptibility to injury in adolescents. To elucidate the mechanism underpinning the testicular effects of DEHP in puberty, we sought to investigate the JAZF1/TR4 pathway in the testes of pubertal rats. Specifically, we focused on the role of the JAZF1/TR4 pathway in male reproduction, including the genes JAZF1, TR4, Sperm 1, and Cyclin A1. In the present study, rats were exposed to increasing concentrations of DEHP (0, 250, 500, and 1000 mg/kg/day) by oral gavages for 30 days. Then we assayed testicular zinc and oxidative stress levels. Our results indicated that DEHP exposure could lead to oxidative stress and decrease the contents of testicular zinc. Additionally, significant morphological changes and cell apoptosis were observed in testes exposed to DEHP, as identified by hematoxylin and eosin staining and the terminal deoxynucleotidyl transferase-mediated nick and labeling assay. By measuring the expression levels of the above relevant genes by qPCR, we found the DEHP-induced increased expression of JAZF1 and decreased expression of TR4, Sperm 1, and Cyclin A1. Therefore, we have demonstrated that in vivo exposure to DEHP might induce reproductive toxicity in pubertal male rats through the JAZF1/TR4 pathway and oxidative stress.

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Reproductive toxicity after levetiracetam administration in male rats: Evidence for role of hormonal status and oxidative stress

PLoS ONE ◽

10.1371/journal.pone.0175990 ◽

2017 ◽

Vol 12 (4) ◽

pp. e0175990 ◽

Cited By ~ 13

Author(s):

Merve Baysal ◽

Sinem Ilgin ◽

Gozde Kilic ◽

Volkan Kilic ◽

Seyda Ucarcan ◽

...

Keyword(s):

Oxidative Stress ◽

Reproductive Toxicity ◽

Male Rats ◽

Hormonal Status ◽

And Oxidative Stress

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Olanzapine induced reproductive toxicity in male rats

Scientific Reports ◽

10.1038/s41598-021-84235-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Cankız Mina Ardıç ◽

Sinem Ilgın ◽

Merve Baysal ◽

A. Burak Karaduman ◽

Volkan Kılıç ◽

...

Keyword(s):

Oxidative Stress ◽

Histopathological Examination ◽

Reproductive Toxicity ◽

Sperm Concentration ◽

Toxic Effects ◽

Male Rats ◽

Control Group ◽

Oxidative Stress Biomarkers ◽

Serum Lh ◽

Testis Tissue

AbstractAlthough it is reported that olanzapine (OLZ), which is an atypical antipsychotic drug, causes sexual dysfunction in men, it is noteworthy that there is not any study evaluating the toxic effects of OLZ on the male reproductive system. In the scope of this research, it was aimed to assess the reproductive toxic effects of OLZ by oral administration of 2.5, 5, or 10 mg/kg of it to male rats for 28 days. For this purpose, sperm concentration, motility and morphology, and DNA damage were determined, and histopathological examination of testis tissue was carried out in rats. Also, the levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone, which play roles in the regulation of reproductive functions, and the levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) which play roles in reproductive pathologies as oxidative stress biomarkers, were determined. According to the results, normal sperm morphology was decreased in 5 ve 10 mg/kg OLZ-administered groups, and pathological findings were evident in the testicular structure of the OLZ-administered group when compared with the control group. It was determined that serum LH, FSH, and testosterone levels were decreased in the OLZ-administered group. Also, decreases of GSH levels in testis tissue were determined and evaluated as the markers of the oxidative stress induced by OLZ in the testis. In conclusion, it was determined that reproductive toxic effects were induced in rats by OLZ administration. This pathology was accompanied by alterations of the hormone levels and testicular oxidative stress.

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