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- ArticleAçık Erişim2026Investigation of the Protective Effect of Centella asiatica Against Doxorubicin-Induced Testicular Damage in Rats
Bedir, Fevzi; Suleyman, Zeynep; Kocaturk, Huseyin; Altay, Mehmet Sefa; Keskin Cimen, Ferda; Altuner, Durdu; Babayeva, Mansura; Suleyman, Halis
Doxorubicin (DOX) is an antineoplastic agent commonly used in cancer therapy that is known for its testicular toxicity. DOX-induced testicular injury involves inflammation, reactive oxygen species, and oxidative stress. Centella asiatica exhibits anti-inflammatory and antioxidant properties. The present experimental study aimed to determine the potential protective efficacy of Centella asiatica in a rat model of doxorubicin-induced testicular toxicity. Rats were randomly assigned to four groups: healthy control (HC), CA, DOX, and CA + DOX (CADX). An oral dose of 200 mg/kg Centella asiatica was administered to the CA and CADX groups. The HC and DOX groups received saline. One hour later, DOX (7.5 mg/kg) was intraperitoneally injected into the DOX and CADX groups on days 1, 4, and 7. Centella asiatica markedly attenuated the DOX-induced increase in malondialdehyde, nitric oxide, and pro-inflammatory cytokine levels, while preventing the decrease in superoxide dismutase activity in testicular tissue (p < 0.001). Centella asiatica reduced the severity of DOX-induced morphological damage in testicular tissue (p < 0.05). Moreover, it partially restored reproductive hormone function. In conclusion, Centella asiatica demonstrates significant potential in mitigating DOX-induced oxidative damage, attenuating testicular injury and preserving the functional integrity of the male reproductive system.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Protective Effects of Ranolazine in a Rat Model of Ovarian Ischemia/Reperfusion Injury
Admis, Mesut; Sezgin, Esra Tuba; Suleyman, Zeynep; Admis, Ozlem; Ozkaraca, Mustafa; Gungor, Ali; Aliyev, Aydin; Suleyman, Halis
Ovarian ischemia/reperfusion (I/R) injury is a major cause of tissue damage following the surgical detorsion of ovarian torsion and is characterized by excessive oxidative stress, inflammation, and progressive cellular injury. Although ranolazine has been reported to exert antioxidant and anti-inflammatory effects in various experimental models, its potential protective effects against ovarian I/R injury have not yet been investigated. This study aimed to evaluate whether pretreatment with ranolazine protects ovarian tissue against experimental I/R injury in rats. Twenty-four female Wistar albino rats were randomly assigned to four groups: a healthy group (HG), sham-operated group (SOG), ovarian ischemia/reperfusion (OIR) group, and ranolazine-treated ovarian ischemia/reperfusion (ROIR) group. Ovarian ischemia was induced by 1 h of torsion followed by 6 h of reperfusion. Ranolazine (50 mg/kg) was administered 1 h before the induction of ischemia as a preventive pretreatment. Oxidative stress markers (MDA, tGSH, SOD, and CAT), pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), histopathological alterations, and the expression of COX-1, COX-2, IL-1β, and IL-6 were evaluated by double immunofluorescence staining. Ovarian I/R significantly increased MDA and pro-inflammatory cytokine levels while markedly decreasing tGSH levels and SOD and CAT activities (p < 0.001). These biochemical alterations were accompanied by severe follicular degeneration, mononuclear cell infiltration, interstitial edema, decreased COX-1 immunoreactivity, and increased expression of COX-2, IL-1β, and IL-6. Ranolazine treatment significantly attenuated oxidative stress and inflammatory responses, preserved the antioxidant defense system, ameliorated histopathological damage, restored COX-1 immunoreactivity, and inhibited the expression of COX-2, IL-1β, and IL-6. This is the first experimental study evaluating ranolazine in ovarian I/R injury. These findings suggest that preventive pretreatment with ranolazine attenuates experimental ovarian I/R injury through antioxidant and anti-inflammatory mechanisms. Future studies are needed to determine whether similar protective effects can be achieved when ranolazine is administered after ovarian torsion or following surgical detorsion.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026The effect of Hippophae rhamnoides on Hydroxychloroquine-Induced stomatitis in rats
Dilber, Muhammet; Suleyman, Zeynep; Yucel, Nurinisa; Yazici, Gulce Naz; Mammadov, Renad; Cakir, Osman Kagan; Celik, Fatih; Coban, Taha Abdulkadir; Salcan, Ismail; Baykal, Huseyin
Background: Stomatitis is the most common mucosal side effect associated with Hydroxychloroquine (HCQ). Hippophae Rhamnoides (HR) is known to contain several phytonutrients, including anti-inflammatory, and antioxidant properties. This study aimed whether HR can mitigate HCQ-induced oxidative stress and inflammation in rat cheek tissue and to corroborate biochemical findings with macroscopic and histopathological evaluations. Methods: Twenty four rats were used and split into four groups: healthy control group (HG), receiving HR alone, receiving HCQ alone, and receiving both HR and HCQ (HRHQ). The drugs were administered for 10 days, and at the end of the 10th day, the rats were euthanized with high dose of thiopental sodium anesthesia and the inner cheek tissues removed. Results: HR decreased malondialdehyde, and pro-inflammatory cytokine levels, which increased by HCQ, while it increased anti-oxidant levels, which decreased by HCQ. The inner cheek tissue was examined macroscopically for edema, hemorrhagic cracks, hyperemia and gray appearance that developed due to HCQ use, which were alleviated with HR. Histopathologically, epithelial necrosis, muscle degeneration, scar tissue, polymorphonuclear cell (PMNL) infiltration, haemorrhage and edema were observed in the HCQ group. In contrast, in the HRHQ group, epithelial necrosis, and muscle degeneration were normal, haemorrhage was absent, PMNL infiltration persisted in some-areas, and moderate capillary congestion and dilatation were observed. detected. Conclusion: The results indicate that HR may be a potential candidate for preventing and treating stomatitis associated with HCQ use. Translating these findings into clinical practice could support the safe and effective use of HR as a therapeutic agent.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Dose-Dependent Pulmonotoxic Effects of Favipiravir in Rats Biochemical and Histopathological Evaluation
Suleyman, Zeynep; Altuner, Durdu; Suleyman, Halis; Coban, Taha Abdulkadir; Ozkaraca, Mustafa
Background and Objective: Favipiravir is associated with more serious side effects at higher doses. This experimental study proposed to investigate the effect of favipiravir on dose-dependent lung toxicity in rats biochemically and histopathologically. Materials and Methods: The rats were divided into four groups as healthy (HG), 100 mg/kg favipiravir (FAV-100), 200 mg/kg favipiravir (FAV-200) and 400 mg/kg favipiravir (FAV-400). Favipiravir 100, 200 and 400 mg/kg doses were administered by oral gavage to the other groups except HG. To the HG group, only distilled water (0.5 mL) was applied in the same way. This procedure was repeated twice a day for a week. Then, the rats were euthanised with high-dose anaesthesia and lung tissues were removed. Oxidative stress parameters such as malondialdehyde (MDA), Total Glutathione (tGSH), superoxide dismutase (SOD), total oxidant status (TOS) and total antioxidant status (TAS) were examined. After the one-way ANOVA, the Tukey's post hoc test was performed. Results: Favipiravir dose-dependently increased MDA and TOS also decreased tGSH, SOD and TAS in rat lung tissue. As favipiravir was given in increasing doses, it was easier to observe the changes between the different groups. This was also supported by the histopathological data. Histopathologically, interstitial pneumonia and lymphoid hyperplasia were mild in the 100 mg/kg favipiravir group, severe at high doses. Conclusion: As the dose of favipiravir increased, oxidant levels increased and antioxidant levels decreased in the lung tissue. In line with these results, it was observed that favipiravir caused a dose-dependent pulmonotoxic effect in rats.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Protective effect of adenosine triphosphate against cisplatin-induced necrotic and degenerative oral mucositis in rats
Salcan, Ismail; Dilber, Muhammed; Suleyman, Zeynep; Yucel, Nurinisa; Salcan, Sara; Kesan, Sefa; Yazici, Gulce Naz; Celik, Fatih; Koseturk, Merve; Alp, Nurdan Alcan
Inflammation, oxidative damage, and adenosine triphosphate (ATP) depletion play a role in the7 pathogenesis of cisplatin (CIS)-induced oral mucositis. Objective: The purpose of this research is to examine8 the impact of ATP against potential oral mucositis development in cisplatin-treated rats. Methodology All rats9 were randomly assigned to four groups, namely healthy control group (HG), ATP group (ATPG), Cisplatin10 group (CISG), and ATP + Cisplatin group (ATCS). Firstly, ATP 4 mg/kg was administered via intraperitoneal11 injection (IP) to both ATPG and ATCS groups. The same volume of normal saline was injected into HG and12 CISG groups. After 1 h, cisplatin 5 mg/kg was administered via IP to CISG and ATCS groups. The drugs13 were taken 1x1 for 7 d. Later, tongue tissues were collected from all groups. Biochemical, macroscopic,14 and histopathological examinations were performed on all tissues. Results: ATP inhibited cisplatin-induced15 oxidative damage and pro-inflammatory cytokines levels in tongue tissue. In the CIS group, a significant16 number of distinct sulcus formations were found in the apex and corpus, as well as a few ulcer foci in the17 corpus, significant papilla loss, and bleeding. Meanwhile, in the ATP group, a similar appearance to healthy18 tissue was observed. Histopathologically, it was determined that in cisplatin-aggravated tongue tissue19 damage, filiform papillae decreased when ATP was administered, and the arrangement and structures of20 the epithelium, blood capillaries, muscle groups, and adipose cell groups were normal. Conclusions: Oral21 mucositis caused by cisplatin is alleviated by ATP. These findings may be useful for developing new therapeutic22 approaches to prevent or treat mucositis, a side effect so severe that can lead to treatment discontinuation.23 24.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025Effect of adenosine triphosphate on methylphenidate-induced oxidative and inflammatory kidney damage in rats
Yeter, Bahtinur; Suleyman, Zeynep; Bulut, Seval; Cicek, Betul; Coban, Taha Abdulkadir; Demir, Ozlem; Suleyman, Halis
The purpose of this trial was to assess the effects of methylphenidate on the kidney tissues and to investigate the protective effect of adenosine triphosphate (ATP) against possible methylphenidate nephrotoxicity in rats. The rats were separated into; healthy control (HG), methylphenidate (MPHG), ATP (ATPG), and ATP+ methylphenidate (AMPG). The ATPG and AMPG groups were administered ATP 4 mg/kg bw/d, and the HG and MPHG groups received distilled water intraperitoneally. One hour from, ATP and distilled water administration, methylphenidate 10 mg/kg bw/d was applied via oral gavage to the AMPG and MPHG groups once daily for 30 d (1 × 1). Animals were euthanized after 30 d and tissues were collected. The levels of certain oxidant/antioxidant parameters, pro-inflammatory cytokines, and Blood urea nitrogen (BUN) and creatinine levels were measured. Kidneys were also examined histopathologically. ATP inhibited the increase in oxidant and decrease antioxidant levels induced by methylphenidate. The amounts of pro-inflammatory cytokines were increased in methylphenidate-treated kidney tissue compared with the HG and AMPG groups. However, ATP increased oxidative damage markers and cytokines levels close to the healthy group. Serum BUN and creatinine levels increased with methylphenidate but ATP prevented BUN and creatinine from rising in the ATPG and MPHG groups. ATP also reduced the histopathological damage increased by methylphenidate. The potential efficacy of ATP in treating kidney damage induced by methylphenidate use.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Association of Tramadol-Induced Ovarian Damage and Reproductive Dysfunction with Adenosine Triphosphate and the Protective Role of Exogenous ATP Treatment
Gumusburun, Neset; Delibasi, Ilhan Bahri; Bulut, Seval; Suleyman, Halis; Kalkan Yilmaz, Betul; Coban, Taha Abdulkadir; Mendil, Ali Sefa; Suleyman, Zeynep
Background: Tramadol, a weak opioid analgesic agent, is known to induce ovarian damage. Previous studies have held oxidative stress responsible for the adverse effects of tramadol on female reproduction. This study examined the protective effects of ATP against tramadol-induced ovarian damage and reproductive dysfunction in rats. Methods: Rats were divided into four groups (n = 12); healthy (HG), only ATP (ATPG), only tramadol (TMDG), and ATP + tramadol (ATMG). ATP was injected intraperitoneally at 25 mg/kg. Tramadol at 50 mg/kg was initiated one hour after ATP. The treatment was administered once a day for 14 days. Six rats from each group were euthanized. For two months, the remaining rats were paired with male rats. Rats that failed to give birth during this period were considered infertile. A maternity period was calculated for the rats that were delivered. Results: Tramadol caused an increase in malondialdehyde and interleukin-6, and decreased total glutathione, superoxide dismutase, and catalase levels in the ovarian tissue. Furthermore, tramadol disrupted the histological structure of the ovaries, and immunohistochemical staining revealed severe immunopositivity. Tramadol again caused infertility and delayed pregnancy in fertile women. By suppressing biochemical changes, ATP significantly reduced tramadol-induced ovarian damage. Both histopathologically and immunohistochemically, ATP treatment regressed ovarian damage. Additionally, ATP significantly reduced tramadol-induced infertility and maternal delay. Conclusions: The results indicate that tramadol-induced oxidative and inflammatory ovarian injury, infertility, and caspase 3 were suppressed by ATP, as demonstrated by our experimental findings.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Effects of Short- and Long-Term Vortioxetine Administration on Reproductive Function in Female Rats
Bingul, Eda; Hizal, Elif; Keles, Ozgecan; Yucel, Nurinisa; Suleyman, Zeynep; Gunay, Murat; Yasar, Hasan; Suleyman, Halis
Background/Objectives: Vortioxetine is a multimodal antidepressant that modulates serotonergic, noradrenergic, and dopaminergic systems, yet its effects on female reproductive physiology remain incompletely defined. This study investigated how short- and long-term vortioxetine exposure influences reproductive function in female rats, integrating measurements of oxidative-stress biomarkers, catecholamines, and endocrine endpoints (prolactin and corticosterone). Methods: Forty-two female Wistar albino rats were randomized into seven groups (n = 6): healthy control; short-term vortioxetine; long-term vortioxetine; and the same two regimens each combined with metyrosine or metyrapone. Metyrosine and metyrapone (50 mg/kg, oral gavage) were given 1 h before vortioxetine (10 mg/kg). Treatments lasted one week (short-term) or four weeks (long-term). Serum MDA, tGSH, SOD, CAT, adrenaline, noradrenaline, dopamine, serotonin, prolactin, and corticosterone were measured. Fertility outcomes were assessed by co-housing females with males for one month. Results: Vortioxetine increased MDA, catecholamines, and serotonin and decreased antioxidant markers and prolactin versus controls (p < 0.001). Long-term vortioxetine produced a marked rise in corticosterone that coincided with infertility and delayed parturition. Metyrosine lowered oxidative stress and catecholamines but did not reverse infertility. In contrast, metyrapone blunted corticosterone elevation and preserved reproductive capacity. Conclusions: Long-term vortioxetine induced infertility in female rats, likely mediated by corticosterone elevation consistent with hypothalamic–pituitary–adrenal axis dysregulation. These findings suggest the need to monitor reproductive risk when considering vortioxetine in women of reproductive age and warrant further mechanistic and translational studies.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Protective effect of adenosine triphosphate against hydroxychloroquine ototoxicity in rats
Erhan, Ertugrul; Suleyman, Zeynep; Altuner, Durdu; Demir, Ozlem; Gulaboglu, Mine; Suleyman, Halis
One of the side effects of hydroxychloroquine is ototoxicity. This study examined the effect of adenosine triphosphate (ATP) on ototoxicity in rats treated with hydroxychloroquine (HCQ). In this study, 24 rats (male, albino Wistar) were used. The animals were divided into four groups: healthy control group (HG), ATP alone group (ATPG), HCQ alone group (HCQG), and ATP + HCQ (AHQG) group. The ATPG and AHQG groups were injected with ATP intraperitoneally (IP) at a dose of 4 mg/kg/day. The HG and HCQG groups were treated with the same volume of saline as the solvent by IP route. The AHQG group was administered HCQ orally at a dose of 120 mg/kg/day 1 h after the ATP and saline administration. This procedure was repeated daily for 10 days. The rats were euthanized (50 mg/kg thiopental sodium, IP) and after, vestibulocochlear nerve tissues were removed and the tissue oxidant and antioxidant parameters were studied. The tissues were also subjected histopathological examination. ATP significantly (p < 0.001) suppressed the increase in malondialdehyde associated with HCQ in vestibulocochlear nerve tissues as well as the decrease in total glutathione, superoxide dismutase, and catalase levels. ATP also reduced the severity of oedema, vascular congestion, dilatation, and collagen deposition in degenerated myelinated nerve fibers associated with HCQ. ATP is effective against oxidative damage associated with HCQ in vestibulocochlear nerve tissue.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Effect of Rutin on Pulmonary Injury in Everolimus-Administered Rats Biochemical and Histopathological Evaluation
Demir, Omer Faruk; Suleyman, Zeynep; Suleyman, Halis; Coban, Taha Abdulkadir; Mokhtare, Behzad
Background and Objective: Everolimus is an anticancer agent that inhibits the Mammalian Target of Rapamycin (mTOR). It causes side effect such as pneumonia. This study aimed to evaluate rutin's effect on potential pulmonary injury in everolimus-administered rats biochemically and histopathologically. Materials and Methods: All rats were split into: Healthy (HG), everolimus-treated (EVR) (2 mg/kg) and rutin (50 mg/kg)+everolimus-treated (REV). Rutin was administered to the REV group and physiological saline was given orally tothe EVR and HG groups. As 1 hr later, everolimus 2 mg/kg was administered to REV and EVR groups. The process was repeated daily, 4 times weekly. Then, high dose anaesthesia was used to kill the rats and lung tissue samples were extracted. Oxidative stress and pro-inflammatory cytokine markers were examined and ANOVA test was applied. Results: Oxidative and inflammatory lung damage developed in the everolimus-treated rats. Rutin attenuated this oxidative and pro-inflammatory lung damage induced by everolimus. Rats administered with everolimus developed severe interstitial pneumonia, lymphoid hyperplasia and desquamation in lung tissues. This severe damage was reduced to mild level by administering rutin. Conclusion: The adding rutin to the treatment regimen for pulmonary damage associated with everolimus may have a preventive impact.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Effect of thiamine pyrophosphate on oxidative damage in the brain and heart of rats with experimentally induced occlusion of the common carotid artery.; [Efecto del pirofosfato de tiamina sobre el daño oxidativo en el cerebro y el corazón de ratas con oclusión inducida experimentalmente de la arteria carótida común.]
Emir, Izzet; Suleyman, Zeynep; Suleyman, Halis
It is known that a sudden increase in cerebral blood flow (hyperper-fusion) with carotid revascularisation may disrupt and damage the blood-brain barrier. This study aimed to explore thiamine pyrophosphate’s (TPP) protective effects against potential brain and heart damage resulting from carotid cross-clamping and unclamping in rats. The animals were divided into common carotid cross-clamping and unclamping (CCU), TPP+common carotid cross-clamping and unclamping (TCCU), and sham operation (SG) groups. The TCCU group received an intraperitoneal injection (IP) of 20 mg/kg TPP one hour before anesthesia. The CCU and SG groups received distilled water as a solvent. Ischemia was induced by maintaining the clips closed for 10 min. For the SG group, only a subcutaneous incision was made. Afterward, the clips were removed, the incisions were stitched, and reperfusion was continued for six hours. Subsequently, the rats were euthanized with high-dosage general anesthesia, and heart and brain tissues were removed. TPP significantly suppressed the I/R-induced malondialdehyde (MDA) increase and decreased total glutathione (tGSH) levels in brain and heart tissues. TPP prevented the increase of tumor necrosis factor-alpha (TNF-α), interleukin-1 β (IL-1β), and interleukin-6 (IL-6) levels in both brain and heart tissues. In blood serum, TPP suppressed I/R-induced increase in troponin I (TP I) and creatine kinase-MB (CK-MB) in the blood. TPP was shown to protect the brain and distant cardiac tissues against oxidative and inflammatory damage induced by cerebral I/R.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Adverse effects of metamizole on heart, lung, liver, kidney, and stomach in rats
Ciftel, Sedat; Suleyman, Bahadir; Mammadov, Renad; Coskun, Resit; Coban, Taha A.; Mokhtare, Behzad; Suleyman, Halis; Cerrah, Serkan; Cicek, Betul; Suleyman, Zeynep
Background: Metamizole is banned in some countries because of its toxicity, although it is widely used in some European countries. In addition, there is limited information on its safety profile, and it is still debated whether it is toxic to the heart, lungs, liver, kidneys, and stomach. Aims: Our study investigated the effects of metamizole on the heart, lung, liver, kidney, and stomach tissues of rats. Methods: Eighteen rats were divided into three groups, wassix healthy (HG), 500 mg/kg metamizole (MT-500), and 1000 mg/kg metamizole (MT-1000). Metamizole was administered orally twice daily for 14 days. Meanwhile, the HG group received pure water orally. Biochemical, histopathologic, and macroscopic examinations were performed on blood samples and tissues. Results: Malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) in the lung and gastric tissues of MT-500 and MT-1000 groups were almost the same as those of the HG (p > 0.05). However, MDA levels in the heart and liver tissues of MT-500 and MT-1000 groups were higher (p < 0.05) compared to the HG, while tGSH levels and SOD, and CAT activities were lower (p < 0.05). MDA levels of MT-500 and MT-1000 groups in the kidney tissue increased the most (p < 0.001), and tGSH levels and SOD and CAT activities decreased the most (p < 0.001) compared to HG. Metamizole did not cause oxidative damage in the lung and gastric tissue. While metamizole did not change troponin levels, it significantly increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels compared to HG. Histopathologically, mild damage was detected in heart tissue, moderate damage in liver tissue, and severe damage in renal tissue. However, no histopathologic damage was found in any groups’ lung and gastric tissues. Conclusion: Metamizole should be used under strict control in patients with cardiac and liver diseases and it would be more appropriate not to use it in patients with renal disease.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024The hormonal mechanism of the effects of meperidine, sertraline, tianeptine, and their combinations on reproductive functions in female rats
Yilmaz, Betul Kalkan; Suleyman, Zeynep; Suleyman, Bahadır; Mammadov, Renad; Bulut, Seval; Altuner, Durdu; Alptekin, Okay; Coban, Taha Abdulkadir; Suleyman, Halis
Background: Infertility caused by drugs that inhibit serotonin reuptake has been attributed to serotonin toxicity. Serotonin has been linked to cause a rise in prolactin and cortisol. This study examined the effects of meperidine, sertraline, tianeptine and combinations on female rat reproductive function. Methods: Female rats were split into 8 groups (n=7): healthy control (HG), meperidine (MG), sertraline (SG), tianeptine (TG), meperidine+sertraline (MSG), meperidine+tianeptine (MTG), sertraline+tianeptine (STG), meperidine+sertraline+tianeptine (MSTG). Meperidine (20 mg/kg, 2×1) was injected intramuscularly. Sertraline (30 mg/kg, 1×1) and tianeptine (5 mg/kg, 1×1) were given orally. The HG received distilled water as solvent. Treatments continued for 20 days. Then, adult males were added to the rat groups and drug treatment continued for another five days. Blood samples were collected on day 26 for biochemical tests. Results: Total oxidant status (TOS) and total antioxidant status (TAS) were not statistically significant between groups (p>0.05). Meperidine (p<0.001) and sertraline (p<0.001) alone increased prolactin levels in comparison to HG and tianeptine inhibited the increase (p<0.001). While meperidine increased corticosterone levels versus HG (p<0.001), sertraline and tianeptine were close to HG (p>0.05). Number of infertile animals was 6 for meperidine, 3 for sertraline, and none for tianeptine. While the duration of pregnancy in MG (15 days) and SG (15 days) was longer compared to HG (2.86 days), no change was observed in TG (2.5 days). Conclusion: Tianeptine and other serotonin re-uptake stimulants may be useful in the treatment of reproductive dysfunction and infertility due to serotonin re-uptake inhibitor treatment.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2024Effect of Sertraline and Vortioxetine on Stress-Induced Brain Injury in Rats: Biochemical and Histopathological Evaluations
Cim, Emine Fusun Akyuz; Suleyman, Zeynep; Suleyman, Halis; Yazici, Gulce Naz; Coban, Taha Abdulkadir
Objectives: Our aim was to evaluate the comparative effects of sertraline and vortioxetine against stress-induced brain injury in rats. Methods: The rats were assigned to a nonstress group (NSG), stress-treated control (StC), sertraline + stress (SSt), and vortioxetine + stress (VSt) groups. Sertraline and vortioxetine (10 mg/kg) were given orally by gavage to the SSt and VSt groups. One hour later, all animals (except NSG) underwent forced immobilization to establish a stress model (2 hours). The drugs were given once a day for 30 days. The animals were killed with ketamine 150 mg/kg, and tissues were removed from the cerebral cortex. One-way analysis of variance and Fisher post hoc least significant difference were conducted for the analysis. Results: The malondialdehyde (nmol/mL) level was 2.58 ± 0.48 in the NSG, 8.09 ± 0.57 in the StC, 3.84 ± 0.53 in the SSt, and 2.84 ± 0.20 in the VSt group (P < 0.0002). The total glutathione (mmol/g) was 7.15 ± 0.59 in the NSG, 2.41 ± 0.43 in the StC, 4.58 ± 0.26 in the SSt, and 5.98 ± 0.13 in the VSt (P < 0.0002). The total oxidant status (mmol H2O2Eq/L) level was 3.56 ± 0.20 in the NSG, 9.99 ± 0.74 in the StC, 4.97 ± 0.39 in the SSt, and 3.81 ± 0.31 in the VSt (P < 0.0002). The total antioxidant status (mmolTroloxEq/L) level was 8.65 ± 0.37 in the NSG, 3.04 ± 0.22 in the StC, 6.29 ± 0.34 in the SSt, and 7.61 ± 0.40 in the VSt (P < 0.0002). Sertraline reduced pericellular edema in astrocytes and oligodendrocytes and decreased perivascular edema, dilatation, and congestion of blood vessels, whereas these were not seen with vortioxetine. Conclusions: Compared with sertraline, vortioxetine is a neuroprotective antidepressant with higher antioxidant activity and can more effectively prevent stress-induced brain tissue injury.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2023Effect of Thiamine Pyrophosphate upon Possible Metamizole-Induced Liver Injury in Rats
Bedir, Zehra; Erdem, Kezban Tuna Ozkaloglu; Can, Abdullah; Cicek, Betul; Gulaboglu, Mine; Suleyman, Zeynep; Gursul, Cebrail; Mokhtare, Behzad; Ozcicek, Fatih; Suleyman, Halis
Background and Objective: Metamizole is a non-selective cyclooxygenase (COX) inhibitor NSAID with a strong analgesic and spasmolytic effects. It is the most common analgesic in the world. Thiamine pyrophosphate (TPP) protects the liver tissue against oxidative damage. The aim of our study was to analyze the effect of TPP against possible liver injury and dysfunction of metamizole in rats biochemically and histopathologically. Materials and Methods: The animals were grouped as healthy (HG), 500 mg kg(-1) metamizole (MT-500), 1000 mg kgG1 metamizole (MT-1000), 25 mg kg(-1) TPP+500 mg kg(-1) metamizole (TMT-500), 25 mg kg(-1) TPP+1000 mg kg(-1) metamizole (TMT-1000) groups. The TMT-500 and TMT-1000 groups of animals were injected intraperitoneally (ip) at the dose of 25 mg kg(-1) of TPP. Distilled water as the solvent was injected ip to the HG, MT-500 and MT-100 groups. One hour after injecting TPP and distilled water, metamizole 500 and 1000 mg kg(-1) doses were administered orally to the TMT-500 and TMT-1000 groups. The TPP was administered once and metamizole twice a day for 14 days. The animals were euthanized with high-dose anesthesia. The liver tissues excised from the animals were analyzed biochemically and histopathologically. Results: In both doses metamizole significantly increased MDA, ALT and AST levels and decreased tGSH, SOD and CAT levels compared to the healthy group. TPP significantly prevented the decrease of tGSH, SOD and CAT levels and the increase of MDA, ALT and AST levels with metamizole. There was no statistical difference in all of the levels between the TMT-500 and TMT-1000 groups. The histopathological findings indicated TPP significantly suppressed the damage induced by metamizole. Conclusion: The metamizole was possible to cause moderate damage to liver tissue. Therefore, it was considered that the use of TTP to reduce liver toxicity could be clinically beneficial.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Effect of Lercanidipine, Carvacrol and Their Combination on Ischemia and Reperfusion-induced Distant Organ (Heart) Damage in Rats
Emir, Izzet; Altuner, Durdu; Suleyman, Bahadir; Mammadov, Renad; Suleyman, Zeynep; Coskun, Resit; Coban, Taha Abdulkadir; Suleyman, Halis
Background and Objective: Ischemia/reperfusion (I/R) damage has still been a reason for high morbidity and mortality for patients. Systemic damage is also observed in addition to local damage in lower extremity I/R event. It was purposed to research the protective effect of lercanidipine, carvacrol and lercanidipine, carvacrol their combination (LCC) against cardiac damage possible to develop after the I/R procedure administered to the lower extremities in rats. Materials and Methods: All rats were assigned into five groups, as sham operation (SG), only performed ischemia/reperfusion (I/R) to the lower extremity (IRG), lercanidipine+I/R (LIR), carvacrol+I/R (CIR) and lercanidipine, carvacrol combination+I/R (LCIR), randomly. One hour prior to anesthesia, 10 mg kg(-1) of lercanidipine was given to the LIR group. Carvacrol (50 mg kg(-1)) was injected to the CIR group. Lercanidipine (10 mg kg(-1)) was administered and carvacrol (50 mg kg(-1)) to the LCIR group. In IRG, LIR, CIR and LCIR groups, the ischemia was induced-occluding the femoral-artery for 4 hrs, reperfusion was for 24 hrs. Results: It was observed that malondialdehyde (MDA), troponin I (TPI), Creatine Kinase (CK-MB) and Interleukin 6 (IL-6) levels were lower in the heart tissue applied to LCC and total glutathione, superoxide dismutase and catalase levels were higher than the ones in the groups treated with lercanidipine and carvacrol. Conclusion: Current study suggested that lercanidipine and carvacrol were efficient in the treatment of heart injury, but LCC provided a more efficient treatment. These findings indicated that LCC alone was possible to be better than lercanidipine and carvacrol in reducing the severity of I/R-induced heart damage that occurred in any part of the body.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023The role of Hippophae rhamnoides L. on 5-fluorouracil-ınduced oral mucositis in rats
Dilber, Muhammet; Suleyman, Bahadir; Mammadov, Renad; Suleyman, Zeynep; Yavuzer, Bulent; Gulaboglu, Mine; Erhan, Ertugrul; Salcan, Ismail; Suleyman, Halis
Current study aimed to research the effect of Hippophae rhamnoides (HRE) on potantial oral oxidative and inflammatory damage of 5-FU in rats. The rats were assigned to three groups; healthy (HG), 5-FU 100mg/kg (FUG) and HRE 50mg/kg +5-FU 100mg/kg (HRFU). The 5-FU was injected in the FUG group intraperitoneally. The HRFU was injected 5-FU at 100mg/kg IP one hour after the 50mg/kg HRE was given orally. Olive oil was used as a solvent for the HG. HRE was given to the rats three times a day for ten days. 5-FU was given one dose on the 1st, 3rd and 5th days. On the 10th day, the tissues removed from the animals were euthanized with high-dose anaesthesia and were macroscopically examined. The levels of the oxidant, antioxidant and proinflammatory cytokines were investigated.It was seen that HRE alleviated the symptoms of severe mucositis by antagonizing the effects of 5-FU on oxidant, antioxidant and proinflammatory cytokines such as malondialdehyde, total glutathione, superoxide dismutase, catalase, nuclear factor kappa-B and interleukin-6 in inner cheek and tongue tissue. These results recommend that HRE may be benefical in the cure of 5-FU-associated oral mucositis.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023The effect of carvacrol on the proinflammatory cytokines, histology, and fertility outcome of cisplatin-related ovarian change in a rat model
Dinc, Kemal; Ozyurt, Ramazan; Coban, Taha Abdulkadir; Yazici, Gulce Naz; Suleyman, Zeynep; Yavuzer, Bulent; Suleyman, Halis
Objective: In women, agents used in chemotherapy treatment have side effects such as accelerating follicular depletion and early menopause. Thus, cytotoxic treatments may cause various effects ranging from partial damage to the ovary to premature ovarian failure (POI) and infertility. This study aimed to investigate the protective effect of carvacrol on cisplatin (CIS)-induced reproductive toxicity in female rats. Materials and methods: The animals were divided to four groups; a healthy group (HG), administered only cisplatin 2.5 mg/kg (CIS); cisplatin 2.5 mg/kg + carvacrol mg/kg (CC-50), and cisplatin 2.5 mg/kg + carvacrol 100 mg/kg (CC-100). In this study, the CC-50 and CC-100 groups were injected with carvacrol at 50 and 100 mg/kg intraperitoneally (IP). The CIS and HG groupswere administered normal saline as a solvent in the same way. One hour afterwardthe CC-50 and CC-100 groups were injected with cisplatin at 2.5 mg/kg IP. This procedure was continued once a day for 14 days. At the end of this period, six rats from each group were euthanized with high-dose anaesthesia. Biochemical (oxidant-antioxidant and proinflammatory cytokines) and histopathological examinations were performed on the right ovarian tissue removed from the dead rats. The remaining (n = 6 in each group) animals were kept in the laboratory with mature male rats for two months for breeding. Rats that didn't give birth within two months were considered infertile. A one-way ANOVA test was used for the biochemical analysis, the a Kruskal Wallis test was used for the histopathological analysis. Results: It has been observed that cisplatine causes oxidative stress and inflammatory damage in the ovarian tissue of animals and ultimately causes infertility due to this oxidative stress. While carvacrol significantly suppressed cisplatin-related oxidative stress in ovarian tissue at the 50 and 100 mg/kg doses, it could suppress proinflammatory cytokine increase only at thecytokine increase only at the 100 mg/kg dose. In addition, carvacrol significantly reduced the development of cisplatin-related infertility (from 0 to 83.3%) at a dose of 100 mg/kg. Conclusion: These findings suggest that carvacrol at high doses can reduce the harmful effects of cisplatin on the ovary and improve ovarian reserve in rats.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Protective Effect of Adenosine Triphosphate against 5-Fluorouracil-Induced Oxidative Ovarian Damage in vivo
Ozer, Mehmet; Ince, Sefa; Altuner, Durdu; Suleyman, Zeynep; Cicek, Betul; Gulaboglu, Mine; Mokhtare, Behzad; Gursul, Cebrail; Suleyman, Halis
Objective: The aim of our study was to analyze the effect of ATP on possible ovarian damage of 5-FU in rats. Methods: The animals were divided to three groups; healthy group (HG), 5-FU alone group (FUG) and ATP+5-FU administered group (AFU). The ATP 4 mg/kg was injected intraperitoneally (IP) into the AFU group. The same volume of saline (0.9% NaCl) as the solvent was administered intraperitoneally to the HG and FUG groups. One hour after administering ATP and solvent, 5-FU 100 mg/kg was injected intraperitoneally to the animals in the AFU and FUG groups. ATP was administered to the animals once a day for 10 days. On the 1st, 3rd and 5th days of 5-FU, one dose (total of 3 doses) was administered. On day 10, the animals were euthanasia with high-dose anaesthesia and ovarian tissues were removed. The removed ovaries were analyzed biochemically andhistopathological. Result: ATP significantly suppressed both the increase in MDA and IL-6 levels, and the decrease in tGSH, SOD and CAT levels. Treatment with ATP significantly suppressed the severe vacuolization and primordial follicle degeneration induced by 5-FU in our study. Conclusion: ATP was possible to be useful for the treatment of 5-FU-induced ovarian damage.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2023Stress-associated ovarian damage, infertility, and delay in achieving pregnancy and treatment options; [Daño ovárico, infertilidad y retraso en la concepción relacionados con el estrés y opciones de tratamiento]
Aynaoglu Yildiz, Gulsah; Yapca, Omer Erkan; Dinc, Kemal; Gursul, Cebrail; Gundogdu, Betul; Aktas, Mehmet; Suleyman, Zeynep; Bulut, Seval; Suleyman, Halis
Many types of stress, including psychological stress, negatively affect reproductive health. This study aimed to investigate the effects of sertraline (a selective serotonin reuptake inhibitor), cerebrolysin (neuroprotective/neurotrophic), and a combination of both against stress-induced ovarian damage, infertility and pregnancy delay in female rats. The rats were divided into five groups (n=14/each group) as healthy (HG), stress control (StC), stress+sertraline (SS), stress+cerebrolysin (SC), and stress+sertraline+cerebrolysin (SSC). To induce stress, animals (except the HG) were kept in a supine position with their forelimbs and hindlimbs (FIM) tied for one hour. Then, sertraline (20mg/kg) was given orally to the SS. Cerebrolysin (2.5ml/kg) was injected into the SC subcutaneously. Sertraline+cerebrolysin was administered to SSC with the same methods and doses. FIM and drug administration continued for 30 days. Six rats from each group were euthanized with high-dose anesthesia, right and left ovarian tissues were removed, and tissues were examined biochemically and histopathologically. The remaining rats were taken for breeding. Exposure to stress in rats caused an increase in malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) levels and a decrease in total glutathione (tGSH). Stress was related to histopathological damage, infertility, and delayed birth. The sertraline and cerebrolysin combination was the most effective in preventing these changes, with sertraline and cerebrolysin alone in second and third places, respectively. Regarding efficacy, selective serotonin reuptake inhibitors (SSRIs) and related drugs may be beneficial in treating stress-related ovarian damage, infertility, and delay in pregnancy.
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