Diabetes mellitus with the subsequent generation of reactive oxygen species represents a major risk factor for testicular dysfunction (TD). We investigate whether administration of antioxidants edaravone and taurine could prevent type 1 diabetes-induced TD in the rat. Six-week-old male Wistar rats were divided into four groups. Group A was treated with citrate-phosphate buffer plus normal saline, whereas in the other three groups, diabetes was induced by streptozotocin (50 mg/kg intraperitoneally). Subsequently, the diabetic rats were treated for 4 weeks either with normal saline (group B), edaravone (10 mg/Kg/day, intraperitoneally; group C), or taurine (500 mg/Kg/day, intraperitoneally; group D). Body, testicular, and epididymal weight, serum glucose, malondialdehyde levels, 8-Hydroxy-2'-deoxyguanosine(8-OH-dG) levels, testicular catalase activity, and serum testosterone levels were determined. Histological examination and the Johnsen score were used to observe and evaluate, respectively, the morphological changes in the testes. TUNEL assay was used to examine DNA fragmentation. Mating studies were performed in order to evaluate the fertility potential of male rats in each group. Edaravone or taurine treatment prevented significantly the decreased body, testicular, and epididymal weight induced by diabetes. Moreover, edaravone or taurine significantly decreased the diabetes-induced malondialdehyde levels, 8-OHdG levels, the morphological damage, and the number of apoptotic cells. Taurine, but not edaravone, increased significantly the testicular catalase activity. The antioxidant treatment had no effect on the fertility potential of the diabetic rats. The morphological damage, increased lipid peroxidation, and apoptosis in testicular tissue can be significantly relieved by edaravone or taurine treatment through suppressing the increased oxidative stress in the rat testis.
"Our study results and the findings in the literature show that MFMTPs are effective antioxidant agents in the prevention of I/R-associated oxidative damage. However, as discussed above, there are also studies in which antioxidant therapy in diabetic rats has not been shown to have a positive effect on reproductive functions (22). Melatonin can be used for the stimulation of follicular development in animals, to improve oocyte quality, or against damage caused by oxidative stress during pregnancy (54). "
[Show abstract][Hide abstract] ABSTRACT: Objective(s):
This study investigated the effects of melatonin, famotidine, mirtazapine, and thiamine pyrophosphate on ischemia/reperfusion (I/R) injury in diabetic rats and evaluated oxidant and antioxidant marker measurement results. It also examined the effects of the drugs aimed at preventing infertility that may result from I/R injury.
Materials and Methods:
Diabetic rats were divided into a control group (IRC) to be exposed to I/R, an ovarian I/R + 2.2 mg/kg melatonin (IRML) group, an ovarian I/R + famotidine (IRFA) group, an ovarian I/R + 20 mg/kg mirtazapine (IRMR) group, an ovarian I/R + 20 mg/kg thiamine pyrophosphate (IRTP) group, and a sham operation (SO) group.
In the control group exposed to I/R, the levels of the oxidant parameters Malondialdehyde (MDA) and Myeloperoxidase (MPO) were significantly higher compared with the SO group, while the levels of the antioxidant parameters glutathione (GSH), Glutathione peroxidase (GPO), Glutathione reductase (GSHRd), Glutathione S - transferase (GST), and Superoxide dismutase (SOD) were significantly lower. Melatonin, famotidine, mirtazapine, and thiamin pyrophosphate prevented a rise in oxidant parameters and a decrease in antioxidants in ovarian tissue exposed to I/R. However, apart from thiamin pyrophosphate, none of the drugs were able to prevent infertility caused by I/R injury.
Prevention of ovarian I/R injury-related infertility in rats with induced diabetes is not through antioxidant activity. Thiamine pyrophosphate prevents infertility through an as yet unknown mechanism. This study suggests that thiamine pyrophosphate may be useful in the prevention of I/R-related infertility in diabetics.
Iranian Journal of Basic Medical Sciences 04/2014; 17(4):294-302. · 1.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: During early development, apoptosis plays a major role in the ontogeny of the germ line as a means of regulating the germ cell:Sertoli cell ratio. In the adult, apoptosis fulfils another function in removing damaged germ cells from the seminiferous epithelium in response to a wide range of physiological and environmental triggers. These include various forms of electromagnetic radiation, chemotherapeutic agents and commonly encountered toxicants such as phthalate esters, bisphenol A and cadmium. This form of apoptosis can lead to spermatogenic arrest and is predominantly mediated by the Fas/FasL system. In addition, senescent mature spermatozoa can undergo a truncated form of apoptosis in order to ensure their efficient phagocytosis within the male and female reproductive tracts. This apoptotic cascade appears to be triggered by oxidative stress and lipid peroxidation, which leads to activation of mitochondrial reactive oxygen species (ROS) generation in a self-perpetuating redox cycle. The electrophilic aldehydes generated as a result of lipid peroxidation also lead to a rapid loss of sperm motility followed some hours later by caspase activation and phosphatidylserine exposure on the sperm surface. The nuclear DNA suffers oxidative damage during this process but there is no immediate DNA cleavage by endonucleases as there is in somatic cells. The reasons for this deviation from the normal pattern of apoptosis involve the unusual physical architecture of spermatozoa and the limited capacity these cells possess for base-excision repair. These findings have practical implications for the approaches that might be used to detect and prevent DNA damage in spermatozoa.
The International journal of developmental biology 06/2013; 57(2-3-4):265-272. DOI:10.1387/ijdb.130146ja · 1.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To investigate diabetes mellitus (DM)-induced oxidative DNA damage, putative involvement of angiotensin (Ang) II, and possible modulatory effects of Ang-(1-7) in rat corpus cavernosum (CC). DESIGN: In vivo study. SETTING: Research laboratory. ANIMAL(S): Adult male Wistar rats. INTERVENTION(S): Streptozotocin-induced diabetic rats received either captopril, losartan (both 300 mg/L in drinking water), or Ang-(1-7) (576 μg/kg/d IP) for a 3-week period immediately before sacrifice at 6 weeks of DM. MAIN OUTCOME MEASURE(S): Histopathological changes in CC were examined in Masson's trichrome-stained tissue sections. Oxidative stress was evaluated by measuring total oxidant status and antioxidant status. The DNA damage was estimated by measuring 8-hydroxy-2'-deoxyguanosine by immunohistochemistry and ELISA. RESULT(S): The CC smooth muscle degeneration was observed in association with an increase in total oxidant status and a decrease in total antioxidant status in rats with DM. Oxidative DNA damage was significantly increased in both cytoplasm and nuclei of CC in DM. Treatment with captopril, losartan, or Ang-(1-7) inhibited these changes in rats with DM. CONCLUSION(S): The data indicate that Ang II signaling is involved in DM-induced structural changes and oxidative DNA damage in the CC and that modulation of the signaling by captopril, losartan, and Ang-(1-7) restores the effects of DM. Thus, Ang-(1-7)/MAS1 axis may be a novel therapeutic target for erectile dysfunction in DM.
Fertility and sterility 03/2013; 100(1). DOI:10.1016/j.fertnstert.2013.02.046 · 4.59 Impact Factor
Eleni Pontiki, Dimitra Hadjipavlou-Litina, Alexandros Patsilinakos, Trang M Tran, Charles M Marson
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