Thymoquinone is a protective agent that reduces the negative effects of doxorubicin in rat testis

2020 ◽  
Vol 39 (10) ◽  
pp. 1364-1373 ◽  
Author(s):  
E Öztürk ◽  
E Kaymak ◽  
AT Akin ◽  
D Karabulut ◽  
H Murat Ünsal ◽  
...  

Background: Doxorubicin (DOX) is used for treatment of many cancer types. Thymoquinone (THQ) is a powerful antioxidant agent used for reducing side effects of several drugs. The aim of this study is to determine possible therapeutic effects of THQ on doxorubicin-induced testicular toxicity in rats. Methods: Rats were divided into five groups ( n = 8): control, THQ, olive oil, DOX (a single dose of 15 mg/kg intraperitoneally (i.p.) on seventh day of the experiment), and DOX + THQ (10 mg/kg THQ per day and 15 mg/kg DOX i.p. on seventh day). Animals were euthanized, and testis tissues were evaluated histopathologically. Caspase 3 and HSP90 immunostaining were performed to determine the expression levels of these proteins among groups. Terminal deoxynucleotidyl transferase 2′-deoxyuridine, 5′-triphosphate nick-end labeling method was used for evaluation of apoptotic index. Moreover, serum testosterone levels and total antioxidant status (TAS) and total oxidant status (TOS) in testicular tissue were measured by ELISA assay. Results: The DOX group had histopathological deterioration compared to the control group. There was an increase in apoptotic index, caspase 3 and HSP90 expressions in the DOX group. While TAS level of the DOX group decreased, TOS level increased when compared with the other groups. Serum testosterone levels in the DOX group decreased compared to the control group. However, there was improvement in testicular tissue in DOX + THQ group compared to the DOX group. There was a decrease in apoptotic index, caspase 3, and HSP90 expressions in DOX + THQ group compared to the DOX group. Testosterone level of DOX + THQ significantly increased compared to the DOX group. Conclusion: We suggest that THQ can be used as a protective agent to reduce the toxic effects of DOX.

2005 ◽  
Vol 21 (9) ◽  
pp. 249-254 ◽  
Author(s):  
Oğuz Aslan Özen ◽  
Nusret Akpolat ◽  
Ahmet Songur ◽  
İlter Kuş ◽  
İsmail Zararsiz ◽  
...  

One parameter which might provide an insight into the underlying mechanism of the effect of formaldehyde (FA) inhalation on testicular tissue, is the assessment of heat shock protein 70 (Hsp70), which increases promptly in cells exposed to stress caused by chemical toxicity. Thus, following subchronic exposure at cytotoxic concentrations, we studied the immunohistochemical effect of FA inhalation on changes in Hsp70 content in testicular tissue. We used 18 albino Wistar rats divided into three groups, exposed to 0 (control), 5 and 10 ppm FA gas for a total of 91 days, 8 h/day, five days a week. Serum testosterone levels were determined using a chemiluminescent enzyme immunoassay. Testicular tissues were stained with Hematoxylin-Eosine and Hsp70 immunohistochemically performed. Diameters of seminiferous tubules and serum testosterone levels in animals inhaling FA were significantly decreased. In seminiferous epithelium stained for Hsp70, compared to those in the control group, the spermatogenetic cells in the experimental groups demonstrated an obvious increase in immunoreaction spermatides in the adluminal region and especially in the cytoplasm of spermatocytes. Immunoreaction of Hsp70 was detected in the spermatogonias of animals exposed to FA inhalation as opposed to those of the control group. Compared to the control, there was a significant increase in the immunoreactions observed not only in the cytoplasm of primary spermatocytes, but also spermatides in the adluminal region of the seminiferous tubules. In conclusion, FA gas may damage spermatogenetic cells and increase Hsp70 synthesis.


2016 ◽  
Vol 36 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Yasemin Yuksel ◽  
Ramazan Yuksel ◽  
Murat Yagmurca ◽  
Hacer Haltas ◽  
Husamettin Erdamar ◽  
...  

Objective: This experimental study was conducted to elucidate the possible protective/therapeutic effects of quercetin against methotrexate (Mtx)-induced kidney toxicity with biochemical and histopathological studies. Methods: Twenty-four adult male rats were randomly divided into four groups, as follows: control group (saline intraperitoneally (i.p.), 9 days), Mtx group (20 mg/kg i.p., single dose), Mtx + quercetin group (50 mg/kg quercetin was orally administered 2 days before and 6 days after Mtx administration) and only quercetin group (50 mg/kg oral, 9 days). Structural changes were evaluated by hematoxylin–eosin and periodic acid–Schiff stainings. Apoptotic changes were investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and caspase-3 antibody. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured in tissue and plasma samples. Results: Mtx compared with the control group, there was significant increase in nephrotoxic tissue damage findings, in addition to apoptotic index (APOI) and caspase-3 expression ( p < 0.05). Mtx + quercetin group revealed significantly lower histopathological damage and APOI and caspase-3 expression decreased when compared to Mtx group. MDA levels were increased in Mtx group compared to others, and by the use of quercetin, this increase was significantly reduced. SOD levels were higher in Mtx group than others. This increase was evaluated as a relative increase arising from oxidative damage caused by Mtx. Conclusion: As a result, Mtx administration may involve oxidative stress by causing structural and functional damage in kidney tissue in rats. Quercetin reduced the Mtx-induced oxidative stress through its antioxidant properties and so quercetin may be promising to alleviate Mtx-induced renal toxicity.


2020 ◽  
Vol 36 (2) ◽  
pp. 84-92
Author(s):  
Ayşe Başardı Gökçe ◽  
Banu Eren ◽  
Dilek Sağir ◽  
Burcu Demirel Yilmaz

In this study, the effects of a potent antioxidant, selenium, on apoptosis induced by acrolein, a cytotoxic and genotoxic environmental pollutant, were investigated by immunohistochemical and electron microscopic methods. One hundred adult male Wistar albino rats were used in the study. The rats were divided into four main groups: control, acrolein, selenium, and acrolein + selenium. The animals in the experimental groups were given 1 mg/kg/day selenium and 4 mg/kg/day acrolein daily for 7 days by gavage. After drug administration, each group was divided into subgroups according to the time they were to be euthanized: 12th hour, 1st, 2nd, 3rd, and 5th day. The rats in each group at the determined time were euthanized and their livers were removed. Routine histological procedures were performed for light and electron microscopy examinations. After applying the Terminal Deoxynucleotidyl Transferase dUTP nick end labeling assay on the liver sections, apoptotic index values were calculated. Comparing the liver sections of the rats in the acrolein group and the control group, acrolein was found to cause a significant increase in the apoptotic index. The apoptotic index values of the acrolein + selenium group decreased compared to the acrolein group. In the electron microscopic examinations, apoptotic findings were observed in the liver tissues of the rats given acrolein, such as chromatin condensation in the nucleus of hepatocytes, dilatations in the perinuclear space, and cytoplasmic vacuolization. These apoptotic findings were not observed in the acrolein + selenium group after the 12th hour. These findings show that selenium may potentially be useful as a protective agent for people exposed to acrolein.


2021 ◽  
Author(s):  
arzu gezer ◽  
Ebru KARADAĞ SARI

Abstract Roflumilast (ROF) (3-cyclo-propylmethoxy-4-difuorome-thoxy-N-[3,5-di-chloropyrid-4-yl] benzamide) is a second generation and forcible phosphodiesterase-4 (PDE4) inhibitor. This study aims to investigate the effects of chronic Roflumilast in different doses on testicular tissue and testosterone levels in healthy Sprague-Dawley rats. During the research, the 6 weeks old (180–200 gr), 36 male rats were divided into 4 groups. Roflumilast (ROF) was administered as 0.5 mg/kg and 1 mg/kg by oral gavage for four weeks, once each day. Hematoxylin-Eosin (H&E) staining for histopathological examinations in testicular tissue, immunohistochemical and immunofluorescence examinations for Caspase-3, Apoptosis Inducing Factor (AIF) and Light Chain 3β (LC3B) expression levels, and ELISA method used to determine serum testosterone levels. Data were analyzed using SPSS v.22 with Kruskal-Wallis, Mann Whitney-U, and Wilcoxon tests. Roflumilast group lost weight compared to the control and sham. Shedding in the seminiferous epithelium, degenerations in the interstitial area, separation between cells, desquamation, interstitial edema and degenerative changes in the testicular tissue was observed. While apoptosis and autophagy determined by Caspase-3, AIF and LC3B were close and statistically insignificant in control and sham, there was significantly increased apoptotic and autophagic changes and immunopositivity in the ROF groups. The 1 mg/kg Roflumilast group’s serum testosterone level was lower than control, sham and 0.5 mg/kg Roflumilast groups. When the research data was evaluated, it was determined that the chronic use of the active ingredient Roflumilast, which has a broad-spectrum area such as COPD, arthritis, neurodegenerative diseases, liver and dermatology, had negative effects on the testicular tissue and testosterone level of rats.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Tarik Emre Sener ◽  
Beste Melek Atasoy ◽  
Ozge Cevik ◽  
Ozlem Tugce Cilingir Kaya ◽  
Sule Cetinel ◽  
...  

AbstractObjectivesTo investigate the possible protective effects of resveratrol against oxidative testicular damage due to scattered radiation during pelvic ionizing radiation exposure in rats.MethodsRats were divided into 5 groups; control, radiation, and radiation + resveratrol therapy in early and late periods. Under anesthesia, 20 Gy ionizing radiation was applied to prostatic region. Resveratrol was administered (10 mg/kg/day) orally before ionizing radiation exposure. Animals were decapitated at the end of 1st and 10th weeks. Biochemical markers of oxidative stress; caspase-3 and sirtuin-1 protein expressions; testosterone levels were evaluated, histological examinations were performed.ResultsSignificant increases in malondialdehyde, 8-hydroxy-deoxyguanosine levels, myeloperoxidase, and caspase-3 activities were observed after ionizing radiation exposure, also superoxide dismutase and glutathione activities were significantly decreased. Radiotherapy increased caspase-3 and decreased sirtuin-1 protein expressions. Resveratrol treatment significantly reversed these parameters and also reversed the decrease in testosterone levels back to control levels in late period.ConclusionResveratrol showed antioxidant and sirtuin-activating properties against oxidative damage caused by scattered radiation to testis and provided hormonal protection. These results suggest that resveratrol may be an alternative protective agent on testicular tissues against the effects of scattered pelvic radiation.


2016 ◽  
Vol 40 (3-4) ◽  
pp. 621-632 ◽  
Author(s):  
Qing Zhao ◽  
Jianyong Yin ◽  
Zeyuan Lu ◽  
Yiwei Kong ◽  
Guangyuan Zhang ◽  
...  

Background: Sulodexide is a powerful antithrombin agent with reno-protective property. However, whether it has beneficial effects on Contrast-Induced Nephropathy (CIN) remained elusive. In the current study, we evaluated the therapeutic effects of Sulodexide on CIN and investigated the potential mechanisms. Methods: CIN model was induced by intravenous injection of indomethacin, followed by Ioversol and L-NAME. Sprague-Dawley rats were divided into 4 groups: control group, CIN group, CIN+vehicle group (CIN rats pretreated with vehicle) and CIN+ Sulodexide (CIN rats pretreated with Sulodexide). Sulodexide or an equivalent volume of vehicle was intravenously delivered 30 min before the induction of CIN. All the animals were sacrificed at 24h after CIN and tissues were harvested to evaluate renal injury, kidney oxidative stress and apoptosis levels. Plasma antithrombin III (ATIII) activities were also measured. Results: Compared to the untreated CIN group, improved renal function, reduced tubular injury, decreased levels of oxidative stress and apoptosis were observed in CIN rats receiving Sulodexide injection. In addition, we also found that ATIII activity was significantly higher in Sulodexide-administered group than that in vehicle-injected CIN rats. For in vitro studies, HK2 cells were exposed to Ioversol and the cyto-protective effects of Sulodexide were also determined. Sulodexide pretreatment protected HK2 cells against the cytotoxicity of Ioversol via inhibiting caspase-3 activity. Preincubation with Sulodexide could also attenuate H2O2-induced increases in ROS, apoptosis and caspase-3 levels. Conclusions: Taken together, Sulodexide could protect against CIN through activating ATIII, and inhibiting oxidative stress, inflammation and apoptosis.


2016 ◽  
Vol 10 (1) ◽  
pp. 12-16
Author(s):  
Duygu Cam ◽  
Ali Osman Saatci ◽  
Serap Cilaker Micili ◽  
Bekir Ugur Ergur ◽  
Revan Yildirim Karabag ◽  
...  

Purpose: To evaluate the effect of intravitreal azithromycin on the retina in a newborn rabbit model. Methods: Twelve, two-week old New Zealand albino rabbits were divided into two groups (six in each). The right eyes of six rabbits received 0.75 mg (0.05 mL) azithromycin and the right eyes of the remaining six rabbits 1.5 mg (0.1 mL) azithromycin intravitreally. Left eyes were served as the control and received the same volume of saline. All eyes were enucleated at the third postinjection week. Retinal histology was examined by light microscopy. Apoptosis of the retinal cells was further evaluated by immunohistochemical staining for caspase-3 and in situ terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) of DNA fragments. Results: Light microscopy demonstrated no retinal abnormalities in all eyes. However, retinal nuclear DNA fragmentation was evident in both study groups (33.6% with 1.5 mg and 21.4% with 0.75 mg azithromycin) with the TUNEL method. TUNEL staining ratio was statistically higher only in the second group treated with 1.5 mg azithromycin when compared to the control group (p=0.01 Mann Whitney U test). The ratio of caspase-3 positive cells in the two study groups was 21.5% and 20.2%, respectively. Caspase-3 staining ratio was statistically higher in both study groups when compared to the control eyes (p=0.00, p=0.00 respectively). The difference of TUNEL staining ratio between the two study groups was statistically significant (p=0.028), but there were no statistically significant differences in the two study groups by caspase-3 staining (p=0.247). Conclusion: In newborn rabbits, intravitreal azithromycin injection resulted in an apoptotic activity in the photoreceptor, bipolar and ganglion cells. Immunohistochemical analysis suggested that doses of 0.75 mg and 1.5 mg azithromycin, administered intravitreally might be toxic to the newborn rabbit retina.


2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Zhen-Dong Zhang ◽  
Ya-Jun Yang ◽  
Zhe Qin ◽  
Xi-Wang Liu ◽  
Shi-Hong Li ◽  
...  

Aspirin eugenol ester (AEE) is a new pharmaceutical compound esterified by aspirin and eugenol, which has anti-inflammatory, antioxidant, and other pharmacological activities. The aim of this study was to investigate the protective effect of AEE on paraquat- (PQ-) induced cell damage of SH-SY5Y human neuroblastoma cells and its potential molecular mechanism. There was no significant change in cell viability when AEE was used alone. PQ treatment reduced cell viability in a concentration-dependent manner. However, AEE reduced the PQ-induced loss of cell viability. Flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and 4 ′ 6-diamidino-2-phenylindole (DAPI) staining were used to evaluate cell apoptosis. Compared with the PQ group, AEE pretreatment could significantly inhibit PQ-induced cell damage. AEE pretreatment could reduce the cell damage of SH-SY5Y cells induced by PQ via reducing superoxide anion, intracellular reactive oxygen species (ROS), and mitochondrial ROS (mtROS) and increasing the levels of mitochondrial membrane potential ( Δ Ψ m ). At the same time, AEE could increase the activity of glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) and decrease the activity of malondialdehyde (MDA). The results showed that compared with the control group, the expression of p-PI3K, p-Akt, and Bcl-2 was significantly decreased, while the expression of caspase-3 and Bax was significantly increased in the PQ group. In the AEE group, AEE pretreatment could upregulate the expression of p-PI3K, p-Akt, and Bcl-2 and downregulate the expression of caspase-3 and Bax in SH-SY5Y cells. PI3K inhibitor LY294002 and the silencing of PI3K by shRNA could weaken the protective effect of AEE on PQ-induced SH-SY5Y cells. Therefore, AEE has a protective effect on PQ-induced SH-SY5Y cells by regulating the PI3K/Akt signal pathway to inhibit oxidative stress.


Author(s):  
Davoud Kianifard ◽  
Seyyed Maysam Mousavi Shoar ◽  
Morteza Fallah Karkan ◽  
Ahmed Aly

Background: Quinine (QU) as an anti-malarial drug induces alterations in testicular tissue. Toxic effects of monosodium glutamate (MSG) on the male reproductive system have been recognized. Objective: To investigate the impact of MSG administration on the intensity of gonadotoxicity of QU. Materials and Methods: Sixty eight-wk old Wistar rats weighing 180-200 gr were divided into six groups (n = 10/each): the first group as a control; the second and third groups received low and high doses of MSG (2 & 4 gr/kg i.p.), respectively, for 28 days; the fourth group received QU for seven days (25 mg/kg); and in the fifth and sixth groups, QU was gavaged following the MSG administration (MSG + QU) from day 22 to day 28. Serum testosterone and malondialdehyde (MDA) levels were measured. Testes samples were prepared for tissue MDA levels, histomorphometry, and immunohistochemistry of p53. Sperm analysis was performed on cauda epididymis. Results: Serum and tissue MDA levels were increased in treated groups compared to the control group. This increment was higher in the MSG + QU groups. The testosterone levels were reduced significantly (p < 0.0001) in all treated groups. In addition, histomorphometric indices and tubular epithelium population were reduced significantly (p < 0.0001) in QU, MSG + QU, and consequently in high-dose MSG, QU, MSG + QU groups. All spermatogenic indices were reduced in the treated groups, particularly in the MSG + QU groups. Sperm motility and viability indices were reduced significantly (p = 0.003) in the MSG + QU groups. Finally, the overexpression of p53 was observed in the MSG + QU groups. Conclusion: The administration of MSG before and during QU therapy may intensify testicular tissue alterations. Key words: Male reproductive system, Monosodium glutamate, Quinine hydrochloride, Rat.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16153-e16153
Author(s):  
E. C. Nepomuceno ◽  
F. Quintiliano ◽  
F. S. Lima ◽  
E. Café ◽  
P. Boente

e16153 Background: Surgical castration is the gold standard for hormonal deprivation in metastatic prostate cancer, nevertheless this simple procedure may involve on psychological consequences. According to many studies, it's possible to achieve ischemic lesion in liver tissue beyond sclerosants agents (like alcohol or glycerol), however there are very few reports about the effects of such agents in testicles. These study objectives evaluating histological and morphological characteristics of rat testicles submitted to percutaneous administration of sclerosants agents and also, to compare serum testosterone levels between rats submitted to a surgical orchiectomy or percutaneous injection. Methods: Twenty four rats have been shared in four groups with eight animals each. In group O, rats were submitted to bilateral orchiectomy. In the other groups, rats were submitted to percutaneous administration of a sclerosant agent and orquiectomy after thirty days as follows: Group A, Alcohol injection; Group G - Glycerol; Group S - Saline solution (control group). Serum testosterone level was measured after 15 and 30 days in each animal. Results: There is no complication or death in this series. Rats of groups A and G comparing to control group (group S) had smaller testicular weight (0,8±0,1g; 1±0,2g versus 3,15±0,1g p<0,0000001) and smaller testicular volume (0,16±0,05mL; 0,23±0,11mL versus 2,38±0,05mL p<0,0000001). Testosterone serum levels were as similar in groups A and G (sclerosis) as in group O (orchiectomy). After 15 days testosterone levels were A=2,9±0,74 ng\dL; G=2,8±0,39 ng\dL versus O=2,91±1,46ng\dL p=0,99; and after 30 days were A=2,58±0,4ng\mL, G=2,78±0,3ng\mL versus O=2,7±0,95ng\mL p=0,895). Histological findings show extensive necrosis beyond macrophagic infiltration and no Leydig cells visualized.There is no significantly statistical difference between Alcohol and Glycerol groups. Conclusions: Percutaneous administration of alcohol or glycerol in rats testicles causes atrophy and reduces testosterone serum levels like it occurs after surgical castration. More studies are necessary to evaluate if this minimally invasive procedure may be an alternative to surgical orchiectomy in advanced prostate cancer. No significant financial relationships to disclose.


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