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- ArticleAçık Erişim2026Effects of adenosine triphosphate and reduced glutathione on biochemical, histopathological and immunofluorescence alterations associated with atezolizumab-induced cardiac tissue injury
Yasar, Yesim Kaya; Sezgin, Esra Tuba; Suleyman, Bahadir; Mammadov, Renad; Ozkaraca, Mustafa; Gungor, Ali; Coban, Taha Abdulkadir; Suleyman, Halis
Background – In this study, the potential protective effects of adenosine triphosphate (ATP) and glutathione (GSH) against atezolizumab-induced cardiac injury in rat heart tissue were investigated. Methods – A total of 24 male albino Wistar rats were used in the experiment. The animals were divided into four groups: healthy group adenosine triphosphate + atezolizumab (ATAZ), GSH + atezolizumab (GHAZ), and atezolizumab alone (ATZ). ATP was administered intraperitoneally at a dose of 4 mg/kg, while GSH was administered orally at a dose of 200 mg/kg for 7 days. Atezolizumab was administered intraperitoneally to the experimental groups at a dose of 10 mg/kg twice weekly. At the end of the experiment, malondialdehyde total glutathione (tGSH), superoxide dismutase catalase, interleukin-1β (IL-1β), and interleukin-6 (IL-6) levels in heart tissues were measured using biochemical methods. In addition, histopathological and immunofluorescence examinations were performed. Results – The results showed that oxidative stress and inflammation markers increased, whereas antioxidant parameters decreased in the atezolizumab-treated group. ATP and GSH administration significantly attenuated these changes and exerted protective effects on cardiac tissue. Conclusion – Overall, ATP and GSH ameliorated the biochemical, histopathological, and immunofluorescence changes associated with atezolizumab-induced cardiac injury in this experimental model.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Pathophysiology of sildenafil-induced ocular toxicity in rats and treatment
Cicek, Ibrahim; Caliskan, Busra; Yavuzer, Bulent; Altuner, Durdu; Tastan, Tugba Bal; Coban, Taha Abdulkadir; Karatas, Ezgi; Suleyman, Halis
RESULTS: Sildenafil increased oxidant (malondialdehyde) levels and decreased antioxidant levels (total glutathione, superoxide dismutase, catalase) in rat ocular tissues and caused severe oxidative stress. In addition, sildenafil has been shown histopathologically to cause oxidative damage in retinal layers. ATP treatment suppressed oxidative stress and attenuated histopathological damage in the retinal layers. CONCLUSION: ATP protects retinal tissue against sildenafil-induced ocular oxidative damage in rats and may contribute to the development of novel approaches to prevent or treat this damage.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Comparative Protective Effects of ATP and TPP Against Olaparib-Induced Ovarian Injury in Rats: Insights from Biochemical Parameters, Histopathology, and IRE1α, Cleaved Caspase-3, LC3B, and NF-κB p65 Double Immunofluorescence
Paltaci, Seyma Ilayda; Yilmaz, Nesrin; Kozali Uzun, Sukran; Yavuzer, Bulent; Coban, Taha Abdulkadir; Ozkaraca, Mustafa; Gungor, Ali; Yaqubov, Kamandar; Suleyman, Halis
Background: Olaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor used to treat several malignancies. Previous studies have reported that olaparib may induce ovarian injury by elevating reactive oxygen species and impairing cellular energy homeostasis. ATP is a central regulator of intracellular energy balance and antioxidant defense, whereas thiamine pyrophosphate (TPP), the active form of vitamin B1, supports ATP biosynthesis and possesses antioxidant and anti-inflammatory properties. This study compared the protective effects of ATP and TPP against olaparib-induced ovarian injury in rats. Methods: Twenty-four female Wistar albino rats were randomly assigned to four groups (n=6 each): healthy control (HG), olaparib-only (OLP), ATP plus olaparib (ATOL), and TPP plus olaparib (TPOL). Olaparib (100 mg/kg, orally, twice daily), ATP (5 mg/kg, intraperitoneally, once daily), and TPP (25 mg/kg, intraperitoneally, once daily) were administered for 14 consecutive days. Ovarian tissue levels of oxidant (MDA), antioxidants (tGSH, SOD, CAT), and pro-inflammatory cytokine (IL-6) were determined. Tissue specimens underwent histopathological (follicular and parenchymal degeneration) and double immunofluorescence analyses (IRE1α, cleaved Caspase-3, LC3B, and NF-κB p65 immunopositivity). Results: Olaparib significantly increased oxidant and pro-inflammatory cytokine levels and decreased antioxidant levels. Histopathology revealed severe follicular and parenchymal degeneration, and immunofluorescence analysis showed significantly increased IRE1α, cleaved Caspase-3, LC3B, and NF-κB p65 immunopositivity. Both ATP and TPP pre-treatment significantly attenuated olaparib-induced oxidative stress, inflammatory responses, histopathological injury, and cellular stress marker immunopositivity. ATP demonstrated a more pronounced protective effect than TPP, particularly regarding follicular degeneration suppression and LC3B and NF-κB p65 immunopositivity. Conclusion: Olaparib induced ovarian injury accompanied by oxidative stress, cytokine-mediated inflammation, IRE1α-related endoplasmic reticulum stress, cleaved Caspase-3-related apoptosis, LC3B-related autophagy, and NF-κB-related inflammatory signaling. Both ATP and TPP attenuated olaparib-associated injury, with greater effects for ATP. These findings suggest that maintenance of cellular energy homeostasis may represent a promising strategy for attenuating PARP inhibitor-induced ovarian injury.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2026The role of adenosine triphosphate in the treatment of linezolid-induced ovarian damage and reproductive dysfunction in rats: An investigation into the pathogenesis
Delibasi, Ilhan Bahri; Yavuzer, Bulent; Suleyman, Bahadir; Gumusburun, Neset; Coban, Taha Abdulkadir; Mendil, Ali Sefa; Uyar, Elif Esra; Yucel, Nurinisa; Suleyman, Halis
Linezolid is an oxazolidinone-derived antibacterial agent that inhibits bacterial protein synthesis by binding to the peptidyl transferase center of the 50S ribosomal subunit. This study investigated whether exogenously administered adenosine triphosphate (ATP) mitigates ovarian damage and reproductive dysfunction induced by linezolid in rats. Forty-eight female albino Wistar rats were randomly assigned to four groups (n = 12 each): healthy control (HG), ATP-only (ATPG), linezolid-only (LZDG), and ATP plus linezolid (ATLDG). ATPG and ATLDG received intraperitoneal ATP (4 mg/kg), whereas HG and LZDG received saline (0.9 % NaCl). One hour later, linezolid (125 mg/kg) was administered orally to LZDG and ATLDG, and the regimen was repeated twice daily for 28 consecutive days. At study end, six rats per group were euthanized for ovarian biochemical, histopathological, and immunohistochemical evaluations; prior to euthanasia (i.p. thiopental sodium, 50 mg/kg), blood was collected for serum prolactin and anti-Müllerian hormone (AMH) analysis. For fertility assessment, the remaining six females per group were co-housed with two proven fertile males for seven days and then monitored for pregnancy for one month. Linezolid exposure increased oxidative stress, caused ovarian tissue injury, decreased AMH, elevated prolactin, and resulted in a 66.7 % infertility rate. ATP co-treatment attenuated these alterations and reduced infertility to 33.3 %. These findings suggest that ATP may provide a protective therapeutic approach against linezolid-induced ovarian toxicity and reproductive dysfunction.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Comparative Protective Effects of Anakinra and Tocilizumab in Experimental Ocular Ischemic Syndrome
Karimov, Shavkatbek; Sezgin, Esra Tuba; Mammadov, Renad; Suleyman, Bahadir; Yaqudov, Kamandar; Yazici, Gulce Naz; Coban, Taha Abdulkadir; Suleyman, Halis; Bayrakceken, Kemal
Ocular ischemic syndrome (OIS) is a vision-threatening disorder characterized by retinal ischemia, oxidative stress, and inflammation. In this study, the protective effects of anakinra, an interleukin-1 receptor antagonist, were investigated and compared with those of tocilizumab, an interleukin-6 receptor antagonist. Twenty-four male Wistar rats were randomly assigned to four groups (n = 6 per group): sham-operated (SG), carotid artery clamping/unclamping (CUG), anakinra-treated carotid artery clamping/unclamping (ACUG), and tocilizumab-treated carotid artery clamping/unclamping (TCUG). An experimental ocular ischemic injury model induced by transient bilateral common carotid artery occlusion was established by transient bilateral common carotid artery clamping followed by reperfusion. Retinal tissues were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) levels, and histopathological examinations were performed. OIS markedly increased MDA, TNF-α, IL-1β, and IL-6 levels while significantly decreasing tGSH, SOD, and CAT activities. Both anakinra and tocilizumab attenuated oxidative stress and inflammatory responses; however, anakinra produced notably greater improvements in MDA, tGSH, SOD, and CAT levels. Histopathological evaluation demonstrated that both treatments reduced retinal injury, edema, vascular congestion, and inflammatory cell infiltration. Although retinal architecture appeared slightly better preserved in the anakinra-treated group, histopathological scores were comparable between the treatment groups. These findings suggest that anakinra may attenuate oxidative and inflammatory retinal damage in this experimental ocular ischemic injury model and may provide greater biochemical protection than tocilizumab, whereas histopathological protection was comparable between treatments. Nevertheless, further experimental and clinical studies are required to confirm these findings.
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 Erişim2026Experimental Investigation of Fentanyl Analgesic Potency and Its Relationship with Endogenous Adrenaline Levels in Rats
Ates, Irem; Isik, Bahar; Sezgin, Esra Tuba; Altuner, Durdu; Coban, Taha Abdulkadir; Suleyman, Halis
Purpose: Fentanyl is a synthetic opioid analgesic widely used in perioperative medicine due to its high analgesic potency and short duration of action. Previous studies suggest that the analgesic and anesthetic effects of fentanyl may be associated with endogenous catecholamine levels. This study aimed to evaluate the relationship between fentanyl’s analgesic potency and anesthesia duration and endogenous levels of adrenaline (ADR) and noradrenaline (NDR) in rats, as well as changes in oxidative stress and inflammation markers including malondialdehyde (MDA), total glutathione (tGSH), and interleukin-6 (IL-6). Patients and Methods: Three groups of six rats each were formed: an intact group receiving fentanyl, an intact group treated with metyrosine, and an adrenalectomized group receiving fentanyl. Fentanyl was administered at doses of 2, 15, 30, and 75 µg/kg, and anesthesia duration was recorded following intraperitoneal injection. Analgesic activity was assessed by measuring pain threshold using the paw pressure method, and immobility in the supine position was evaluated as an observational parameter. ADR, NDR, MDA, tGSH, and IL-6 levels were biochemically measured in blood and tissue samples. Results: Fentanyl produced analgesic effects in all experimental groups. However, no distinct anesthetic effect sufficient for surgical procedures was observed. Although the durations of immobility in the supine position were recorded, these observations were not evaluated as a direct measure of anesthetic duration. Different doses of fentanyl did not lead to significant alterations in oxidative stress parameters, antioxidant capacity, or anti-inflammatory cytokine levels across the groups. Conclusion: In conclusion, although the analgesic effect of fentanyl increased in a dose-dependent manner, it was found to be independent of serum ADR and NDR levels. High-dose fentanyl (75 µg/kg) did not induce anesthesia and did not significantly affect oxidative stress markers (MDA, tGSH) or IL-6 levels. The increase in MDA and the decrease in tGSH observed in the absence of adrenal hormones support their indirect antioxidant role. Overall, the findings indicate that fentanyl modulates catecholamine responses depending on dose and hormonal status, while its analgesic effect appears to be primarily mediated through µ-opioid receptor activation.
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 Erişim2025Potential effects of adenosine triphosphate and melatonin on oxidative and inflammatory optic nerve damage in rats caused by 5-fluorouracil
Somuncu, Ahmet Mehmet; Somuncu, Busra Parlak; Ozbay, Ahmet Duhan; Cicek, Ibrahim; Suleyman, Bahadir; Mammadov, Renad; Bulut, Seval; Tastan, Tugba Bal; Coban, Taha Abdulkadir; Suleyman, Halis
• AIM: To investigate the effects of adenosine triphosphate (ATP) and melatonin, which have antioxidant and anti-inflammatory activities, on potential 5-fluorouracil (5-FU)-induced optic nerve damage in rats. • METHODS: Twenty-four rats were categorized into four groups of six rats: healthy (HG), 5-FU (FUG), ATP+5-FU (AFU), and melatonin+5-FU (MFU). ATP (4 mg/kg) and melatonin (10 mg/kg) were administered intraperitoneally and orally, respectively. One hour after ATP and melatonin administration, rats in the AFU, MFU, and FUG were intraperitoneally injected with 5-FU (100 mg/kg). ATP and melatonin were administered once daily for 10d. 5-FU was administered at a single dose on days 1, 3, and 5 of the experiment. After 10d, the rats were euthanized and optic nerve tissues were extracted. Optic nerve tissues were biochemically and histopathologically examined. • RESULTS: ATP and melatonin treatments inhibited the increase in malondialdehyde (MDA) and interleukin-6 (IL-6) levels, which were elevated in the FUG. The treatments also prevented the decrease in total glutathione (tGSH) levels and the superoxide dismutase (SOD) and catalase (CAT) activities (P<0.001). This inhibition was higher in the ATP group than in the melatonin group (P<0.001). ATP prevented histopathological damage better than melatonin (P<0.05). • CONCLUSION: ATP and melatonin have the potential to be used in alleviating 5-FU-induced optic nerve damage. In addition, ATP treatment shows better protective effects than melatonin.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025The effect of methylphenidate on the reproductive function of female rats
Cim, Numan; Cim, Bunyamin; Akyuz Cim, Emine Fusun; Bulut, Seval; Mammadov, Renad; Suleyman, Bahadır; Yucel, Nurinisa; Mendil, Ali Sefa; Coban, Taha Abdulkadir; Suleyman, Halis
Aim: Research on the effects of methylphenidate on female fertility is limited. This study evaluated the effects of methylphenidate on reproductive function, oxidants, antioxidants, proinflammatory cytokines, prolactin, and cortisol in female rats. Methods: Forty-eight albino Wistar female rats were divided into four groups consisting of 12 rats, which were given pure water orally once daily for 7 days (HG-1), 10 mg/kg methylphenidate orally once daily for 7 days (MP-1), pure water orally once daily for 30 days (HG-2), and 10 mg/kg methylphenidate orally once daily for 30 days (MP-2). At the end of the treatment periods, tail vein blood was collected from six rats per group for prolactin and cortisol determination. Subsequently, euthanasia was performed and the ovaries were removed. Ovaries were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α), and immunohistochemically. For breeding, the remaining six rats were mated with male rats for 1 month. Rats that failed to give birth were classed as infertile. Results: A comparison of MP-1 and MP-2 groups to healthy controls revealed an elevation in MDA and corticosterone levels, and a decline in tGSH, SOD, and CAT levels (p < 0.001). Methylphenidate did not affect prolactin, IL-1β, and TNF-α levels (p > 0.05). MP-1 and MP-2 exhibited immunopositivity for 8-hydroxy-2'-deoxyguanosine (8-OHDG). MP-2 rats developed 66.7% infertility while MP-1, HG-1, and HG-2 rats did not. Conclusion: In ovaries, methylphenidate caused oxidative stress, but did not induce inflammation. Long-term use of methylphenidate caused increased cortisol levels and infertility.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Sunitinib’s Effect on Bilateral Optic Nerve Damage in Rats Following the Unilateral Clamping and Unclamping of the Common Carotid Artery
Cicek, Ibrahim; Esenulku, Cenap Mahmut; Somuncu, Ahmet Mehmet; Bulut, Seval; Yucel, Nurinisa; Bal Tastan, Tugba; Coban, Taha Abdulkadir; Suleyman, Halis
Background/objectives: Common carotid artery occlusion can cause oxidant and inflammatory damage to the optic nerve. In this study, the effect of sunitinib was investigated, the antioxidant and anti-inflammatory properties of which have been previously reported and shown to be protective in I/R injury and in preventing bilateral optic nerve ischemia–reperfusion (I/R) injuries after unilateral common carotid artery ligation in rats. Methods: In this study, 18 Albino Wistar male rats were divided into SG (sham-operated), CCU (clamping and unclamping), and SCCU (sunitinib + clamping and unclamping) groups. One hour before the surgical procedures, sunitinib (25 mg/kg, oral) was given to SCCU rats. Anesthesia was induced with ketamine (60 mg/kg, ip) and sevoflurane. The right common carotid arteries of all rats were accessed under anesthesia. While the skin opened in SG rats was closed with sutures, the right common carotid arteries of CCU and SCCU rats were clipped, and an ischemia period was created for 10 min. Then, reperfusion (6 h) was achieved by unclipping. After euthanasia with ketamine (120 mg/kg, intraperitoneally), the right and left optic nerves of the rats were removed and examined biochemically and histopathologically. Results: Malondialdehyde, tumor necrosis factor α, interleukin-1β, and interleukin-6 were increased, and total glutathione levels had decreased in both ipsilateral and contralateral optic nerves (p < 0.05). These changes were more prominent on the ipsilateral side. Similarly, histopathological damage was observed to be more on the ipsilateral side (p < 0.05). Biochemical and histopathological changes were significantly suppressed in rats receiving sunitinib treatment (p < 0.05). Conclusions: Sunitinib may protect optic nerve tissue against I/R injury by reducing oxidative stress and inflammation.
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 Erişim2025Protective Role of Thiamine Pyrophosphate Against Erlotinib-Induced Oxidative and Inflammatory Damage in Rat Optic Nerve
Karatas, Ezgi; Yavuzer, Bulent; Demir, Ozlem; Sezgin, Esra Tuba; Hendem, Engin; Cinici, Emine; Coban, Taha Abdulkadir; Suleyman, Halis
Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib are widely used in non-small-cell lung cancer treatment, and accumulating evidence indicates they can markedly increase ocular toxicity. Nonetheless, whether erlotinib causes optic nerve injury has not been investigated before and remains a subject worth investigating. This study aimed to examine the impact of erlotinib on oxidative stress, inflammation, and histopathological changes in rat optic nerve tissue and evaluate the potential neuroprotective role of thiamine pyrophosphate (TPP). Methods: Twenty-four male Wistar rats were randomly assigned to four groups: healthy control, TPP alone, erlotinib alone, and erlotinib + TPP. Erlotinib (10 mg/kg, orally, on alternate days) and TPP (20 mg/kg, intraperitoneally, daily) were administered for two consecutive weeks. Optic nerve samples were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), followed by histopathological examination. Results: Erlotinib treatment significantly increased MDA, IL-1β, and TNF-α levels while reducing tGSH, SOD, and CAT activity, demonstrating oxidative stress and an inflammatory response. Co-administration of TPP ameliorated these changes by lowering reactive oxygen species, restoring antioxidant capacity, and attenuating inflammation. Histopathological alterations, including astrocyte degeneration, edema, and vascular congestion, were evident after erlotinib exposure but were significantly alleviated when TPP was administered concurrently. Conclusions: Erlotinib induces oxidative and inflammatory optic nerve injury, while TPP co-treatment offers significant neuroprotection. These findings support TPP as a potential adjunct to reduce EGFR-TKI-related ocular toxicity and highlight importance of redox modulation in limiting treatment-associated side effects.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025The relationship between rheumatoid arthritis and epicardial fat thickness, and serum levels of chemerin, adropin, and betatrophin
Ekinci, Bilge; Mertoglu, Cuma; Coskun, Resit; Arslan, Yusuf Kemal; Coban, Taha Abdulkadir; Ozcicek, Fatih
Background. Cardiovascular diseases (CVDs) are highly prevalent among patients with rheumatoid arthritis (RA). Epicardial adipose tissue, serum betatrophin, chemerin, and adropin levels are factors associated with atherosclerosis and cardiovascular involvement. Objectives. This study aimed to investigate the relationship between RA and epicardial fat thickness (EFT), as well as serum betatrophin, chemerin and adropin levels. Materials and methods. This cross-sectional study included 80 patients (62 women and 18 men) diagnosed with RA according to the American College of Rheumatology/The European Alliance of Associations for Rheumatology (ACR/EULAR) 2010 RA classification criteria and 80 healthy controls (64 women and 16 men). Exclusion criteria comprised other autoimmune diseases, CVDs, diabetes mellitus, other endocrine disorders, acute or chronic pancreatic disorders, malignancy, pregnancy, breastfeeding, or antihyperlipidemic drug usage. Serum betatrophin, chemerin and adropin concentrations were measured. Epicardial fat thickness was evaluated with transthoracic echocardiography. Results. Adropin levels were significantly lower in the RA group compared to the control group (p < 0.001). Chemerin levels and EFT were significantly higher in the RA group than in the control group (p = 0.016, p < 0.001, respectively). When assessing the relationship between biomarkers and EFT in RA patients, a strong positive correlation was observed between chemerin and EFT (r = 0.73, p = 0.046) in patients with high disease activity. Conclusions. Epicardial fat thickness, as an indicator of cardiovascular involvement, is higher in patients with RA. Moreover, high chemerin levels and low adropin levels in these patients may be indicative of cardiovascular involvement. Copyright by Author(s)
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025The Relationship Between Tramadol-Induced Oxidative Testis Injury and Reproductive Function Disorder and Adenosine Triphosphate
Bedir, Fevzi; Kocatürk, Hüseyin; Altay, Mehmet Sefa; Mammadov, Renad; Süleyman, Bahadır; Coban, Taha Abdulkadir; Yazici, Gülce Naz; Bulut, Seval; Süleyman, Halis
Tramadol, a central analgesic drug, is used to treat moderate to severe pain but can cause reproductive disorders. The pathogenesis of tramadol-induced reproductive damage may involve increased oxidative stress, pro-inflammatory cytokines, ATP depletion, and reduced antioxidant levels. In this study, subjects were divided into four groups: healthy control (HC), tramadol only (TM), ATP only (ATP), and ATP + tramadol (ATM). ATP was administered intraperitoneally at 4 mg/kg, and tramadol was administered orally at 50 mg/kg. Distilled water was given to the HC group. This regimen was repeated for three weeks. At the end of the treatment, testicular tissues from six rats in each group were analyzed biochemically and histopathologically after euthanasia. The remaining rats’ reproductive functions were evaluated. Long-term tramadol exposure resulted in oxidative stress, inflammation in testicular tissue, and reduced male reproductive capacity. Thinning of seminiferous tubule walls and thickening of basement membrane, irregularity in germ cells, increase in interstitial connective tissue, congestion in vessels, increase in Leyding cells and hyperplasia were found in the TM group. ATP treatment significantly reduced tramadol-induced increases in oxidants and pro-inflammatory cytokines, reversed the decline in antioxidants, and mitigated infertility in testicular tissue. Furthermore, ATP preserved the morphology of the testicular tissue. These findings suggest that ATP may offer therapeutic potential for tramadol-induced infertility.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025The molecular mechanism of the protective effect of tianeptine against ovarian ischemia-reperfusion injury
Kalkan, Betul; Yavuzer, Bulent; Aliyev, Aydin; Cakir, Osman Kagan; Gozen, Fusun; Mendil, Ali Sefa; Coban, Taha Abdulkadir; Suleyman, Halis
Torsion of the ovary is a gynecologic emergency that occurs when the ovary and fallopian tube rotate around the infundibulopelvic ligament, causing ischemic changes in the adnexa. Tianeptine is an atypical antidepressant that has been shown to be effective in treatment-resistant depression and has fewer side effects than other antidepressants. In this study, the protective effect of tianeptine on ovarian ischemia-reperfusion (I/R) injury in female rats was evaluated. Four groups were created from twenty-four female albino Wistar rats before surgery (n = 6/each group): TPG (5 mg/kg/orally tianeptine-only), SG (sham operation), OIR (ovarian I/R), and TOIR (5 mg/kg/orally tianeptine + I/R). One hour before surgery procedures, the TPG and TOIR applied tianeptine. Tianeptine administration procedure was repeated once daily for six days. Under 60 mg/kg intraperitoneal (IP) ketamine and sevoflurane (inhaler) anesthesia, the right ovaries, fallopian tubes, and vessels in the OIR and TOIR groups were clamped by torsion. After 3 h of ischemia, a 6-day reperfusion period was started. Tianeptine administration procedure was repeated once daily for six days. In the SG group, the abdominal cavity was opened and closed with sutures without any intervention on the ovaries. On the seventh day, rats were sacrificed (120 mg/kg ketamine, IP), and ovaries were extracted. Levels of oxidants (malondialdehyde), antioxidants (total glutathione, superoxide dismutase, and catalase), and pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1β, interleukin-6) were measured in excised ovarian tissue. Ovarian tissues also examined histopathologically and immunohistochemically. I/R increased the levels of oxidants and pro-inflammatory cytokines and decreased the levels of antioxidants in rat ovaries. In parallel, histopathologic and immunohistochemical examination of the ovarian tissue revealed the presence of severe (grade 3) oxidative damage. Tianeptine significantly suppressed oxidative stress and pro-inflammatory cytokine increases related with I/R in the ovarian tissue, while also alleviating histopathological damage and oxidative DNA damage. Our experimental results suggest that tianeptine treatment may be effective against I/R-induced ovarian injury.
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 Erişim2024Comparative Investigation of the Effects of Adenosine Triphosphate and Agomelatine Against Acrolein-Induced Oxidative and Inflammatory Lung Injury in Rats
Unver, Edhem; Suleyman, Bahadir; Mammadov, Renad; Bulut, Seval; Altuner, Durdu; Coban, Taha Abdulkadir; Suleyman, Halis
Background and Objective: Acrolein-induced tissue damage has been attributed to oxidative stress and inflammation.This study aimed to determine the effects of adenosine triphosphate (ATP) and agomelatine, two substances known to have antioxidant and antiinflammatory effects, separately and in combination, on possible acrolein-induced lung damage in rats. Materials and Methods: There were 30 albino Wistar rats divided into five groups of six: Healthy (HG), acrolein (AC), ATP+acrolein (ATAC), agomelatine+acrolein (AGAC) and ATP+agomelatine+acrolein (AAAC). The dose of ATP administered intraperitoneally was 4 mg/kg and the dose of agomelatine administered orally was 25 mg/kg. An oral dose of acrolein 3 mg/kg was given 1 hr following the administration of ATP and agomelatine. For 30 days, the treatment protocol was followed once a day. Afterwards, the rats were euthanized and their lungs were removed. Oxidants, antioxidants and pro-inflammatory cytokines were measured in lung tissues. Results: In lung tissues, acrolein increased malondialdehyde, nuclear factor kappa, tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 levels and decreased total glutathione, superoxide dismutase and catalase levels (p<0.001). The ATP+agomelatine, ATP and agomelatine treatments were the most effective at preventing these biochemical changes, respectively (p<0.001). As a result, the biochemical data of the HG and AAAC groups were similar (p>0.05). Conclusion: It could be suggested that both ATP and agomelatine might be effective against the pneumotoxic effects of acrolein, though a combination therapy would be more effective.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Protective Effect of Ramipril Against Oxidant and Proinflammatory Cytokine Damage Induced by Ischemia-Reperfusion in Ovarian Tissue in Rats
Ulug, Pasa; Nayki, Umit; Mammadov, Renad; Bulut, Seval; Tastan, Tugba Bal; Coban, Taha Abdulkadir; Suleyman, Halis
Background: It is known that the increase in oxidants and proinflammatory cytokines, as well as the decrease in antioxidants, play a role in ovarian ischemia-reperfusion (I/R) injury. The antioxidant and anti-inflammatory properties of ramipril have been studied in various diseases. This study aims to investigate the effect of ramipril on I/R-induced ovarian damage in rats. Methods: Rats were divided into healthy (HG), sham (SG), ovary I/R (OIR), and ramipril + ovary I/R (ROIR) groups (n = 6/each group). One hour before the surgical procedures, ROIR was given 2 mg/kg ramipril. The lower abdomen of the SG, OIR, and ROIR was surgically opened. Right ovarian tissues of OIR and ROIR were subjected to 2 hours of ischemia and 6 hours of reperfusion. Then, all animals were euthanized, and their right ovaries were removed. Ovarian tissues were examined for oxidants (malondialdehyde), antioxidants (total glutathione, superoxide dismutase, and catalase), and proinflammatory cytokines (nuclear factor kappa-B, tumor necrosis factor-alpha, interleukin 1 beta, and interleukin-6) analysis was performed. Tissues were examined histopathologically. Results: The ovarian tissue of the OIR, which underwent the I/R procedure, exhibited a significant increase in oxidant and proinflammatory cytokine levels, along with a decrease in antioxidant levels (P < .001). Ramipril suppressed the I/R-induced increase in oxidants and pro-inflammatory cytokines and the decrease in antioxidants (P < .001). Ramipril also attenuated I/R-induced histopathological damage in ovarian tissue (P < .05). Conclusion: Ramipril treatment may be a treatment strategy to protect ovarian tissue against oxidative and inflammatory damage of I/R.
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