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- 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 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 - ArticleYalnız künye2025Comparative study of the protective effects of coenzyme Q10 and cinnamon extract on possible kidney damage and dysfunction of amiodarone in rats
Ekici, Ozgur; Gul, Abdullah; Keskin, Ercument; Bulut, Seval; Suleyman, Bahadir; Mammadov, Renad; Cicek, Betul; Demir, Ozlem; Gunay, Murat; Suleyman, Halis
Background: An increase in free oxygen radicals and proinflammatory cytokines and decrease in intracellular adenosine triphosphate account for the nephrotoxic effect of amiodarone. This study investigated the protective effects of Coenzyme Q10 (CoQ10), cinnamon extract (CE) and the combination of the two (CoCE) on possible amiodarone-induced renal injury in rats. Methods: Thirty male albino Wistar rats were cetegorized into healthy (HG), amiodarone (ADG), CoQ10 + amiodarone (CoQA), CE + amiodarone (CEA), and CoCE + amiodarone (CoCEA) groups. First, CoQ10 (10 mg/kg) and CE (100 mg/kg) were orally given. After 1 h, 50 mg/kg amiodarone was orally given to all groups except for HG. Amiodarone, CoQ10, and CE administration was continued orally at the indicated doses once daily for 10 days.Then, blood samples were collected from all groups to determine creatinine, blood urea nitrogen (BUN), and kidney injury molecule (KIM-1) levels, followed by euthanasia and removal of kidney tissues. Oxidative stress and inflammatory parameters were analysed in the tissue samples. Histopathological examination was also performed on the tissues. Results: Amiodarone increased malondialdehyde levels and decreased total glutathione, superoxide dismutase, and catalase levels (p < 0.001). Amiodarone increased the expression and tissue levels of tissue nuclear factor kappa B, tumor necrosis factor-alpha, interleukin-1β and interleukin-6, and led to increases in serum creatinine and BUN and KIM-1 levels (p < 0.001). Amiodarone also caused histopathological damage (p < 0.001).CoQ10, CE and especially CoCE inhibited biochemical changes and tissue damage (p < 0.001). Conclusion: Although CoQ10, CE, and CoCE effectively prevent amiodarone-induced oxidative and inflammatory nephrotoxicity, CoCE appears to be superior.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025The Protective Effect of Thiamine and Thiamine Pyrophosphate Against Linezolid-Induced Oxidative Liver Damage and Lactic Acidosis in Rats
Isik, Bahar; Ates, Irem; Yucel, Nurinisa; Suleyman, Bahadir; Mendil, Ali Sefa; Sezgin, Esra Tuba; Suleyman, Halis
Linezolid, an antimicrobial agent, has been linked to lactic acidosis, oxidative stress, and liver damage. Oxidative stress is considered to play a key role in this damage. Thiamine pyrophosphate (TPP), the active form of thiamine, may prevent lactate accumulation and enhance aerobic capacity. Therefore, this study aimed to evaluate the protective effect of TPP against possible linezolid-induced liver damage and lactic acidosis in rats. Twenty-four male Wistar albino rats were randomly assigned to four groups (n = 6): healthy control (HG), linezolid (LZD), thiamine plus linezolid (TLZD), and TPP plus linezolid (TPLZD). Thiamine and TPP (20 mg/kg, intraperitoneal (i.p.)) were administered once daily, while linezolid (125 mg/kg, per os (p.o.)) was given twice daily (250 mg/kg/day) for 28 days. Animals were euthanized under high-dose anesthesia (with 50 mg/kg, i.p. thiopental sodium). Liver tissues were analyzed for MDA, tGSH, SOD, and CAT, and examined histopathologically. Blood samples were collected prior to euthanasia to assess lactate, LDH, ALT, AST, and TPP levels. In the LZD group, MDA, lactate, ALT, AST, and LDH levels significantly increased, while tGSH, SOD, CAT, and TPP decreased (p < 0.001). Histopathology showed hydropic degeneration, necrosis, and mononuclear cell infiltration (p < 0.05). Thiamine did not prevent these alterations (p > 0.05), whereas TPP significantly prevented both biochemical and histopathological changes (p < 0.05), indicating its protective efficacy. TPP may offer significant protection against linezolid-induced hepatotoxicity and lactic acidosis.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025Effects of adenosine triphosphate and coenzyme Q10 on potential hydroxychloroquine-induced retinal damage in rats.
Ozbay, Ahmet Duhan; Somuncu, Ahmet Mehmet; Cicek, Ibrahim; Yavuzer, Bulent; Bulut, Seval; Huseynova, Gulbaniz; Tastan, Tugba Bal; Gulaboglu, Mine; Suleyman, Halis
This study aimed to investigate biochemically and histopathologically the protective effect of adenosine triphosphate (ATP) and coenzyme Q10 (CoQ10) against potential hydroxychloroquine (HCQ)-induced retinal damage in rats. Twenty-four male albino Wistar-type rats were randomly separated into four groups: healthy (HG), receiving HCQ (HQG), receiving ATP + HCQ (AHQ), and receiving CoQ10 + HCQ (CoQHQ). ATP (4 mg/kg, intraperitoneal) was given to the AHQ, and CoQ10 (10 mg/kg, oral) to the CoQHQ. Rats in the HQG, AHQ, and CoQHQ were given HCQ (120 mg/kg, oral) 1 h after administering ATP and CoQ10. Treatments continued once a day for seven days. On the 8th day, the rats were sacrificed with 50 mg/kg sodium thiopental, and the eyes were removed. Malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT), and interleukin-6 (IL-6) levels were measured in the retrieved eye tissues and retinal tissues were assessed histopathologically. An increase in MDA and IL-6 levels and a decrease in tGSH, SOD, and CAT levels were detected in the eye tissues of the HQGcompared to the HG. HCQ-induced changes in oxidant and antioxidant levels were significantly suppressed by ATP and CoQ10 treatment. ATP was more successful than CoQ10 in this inhibition. Severe damage was observed in the eye tissues of the HQG group, whereas the damage was mild in the AHQ and moderate in the CoQHQ. Although both ATP and CoQ10 have the potential to be effective in the prevention of HCQ-induced retinal damage through antioxidative activity, ATP appears to be the more preferable treatment approach.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Comparative Investigation of the Effects of Adenosine Triphosphate, Melatonin, and Thiamine Pyrophosphate on Amiodarone-Induced Neuropathy and Neuropathic Pain in Male Rats
Kahramanlar, Agah Abdullah; Ozgodek, Habip Burak; Ince, Ramazan; Yavuzer, Bulent; Admis, Ozlem; Mendil, Ali Sefa; Ekinci, Bilge; Suleyman, Halis
Background: Amiodarone is a widely used class III antiarrhythmic agent, but its use can lead to peripheral neuropathy mediated by mitochondrial dysfunction, oxidative stress, and neuroinflammatory injury, while effective preventive options remain limited. Agents that support mitochondrial energy metabolism, sustain redox balance, and modulate inflammation, including adenosine triphosphate (ATP), melatonin, and thiamine pyrophosphate (TPP), may counteract these mechanisms; however, their relative neuroprotective potential in amiodarone-induced neuropathy remains unclear. This study aimed to comparatively evaluate the effects of ATP, melatonin, and TPP on amiodarone-induced peripheral neuropathy and neuropathic pain in rats. Methods: Thirty male albino Wistar rats were assigned to five groups: healthy; amiodarone (50 mg/kg/orally); amiodarone + ATP (5 mg/kg/intraperitoneally); amiodarone + melatonin (10 mg/kg/orally); or amiodarone + TPP (20 mg/kg/intraperitoneally). Treatments were given once daily for 14 days. Oxidative stress indices (malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT)) and proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-1 Beta (IL-1β), interleukin-6 (IL-6)) were quantified in sciatic nerve by Enzyme-Linked Immunosorbent Assay (ELISA). Paw withdrawal thresholds were measured with the Randall-Selitto test before and after treatment. Histopathology was performed using Hematoxylin-eosin staining. Results: Amiodarone exposure resulted in pronounced elevations in MDA and proinflammatory cytokine levels, accompanied by significant reductions in tGSH, SOD, CAT activities, and paw withdrawal thresholds. ATP, melatonin and TPP ameliorated these alterations to varying degrees. Among them, TPP provided the most robust antioxidant and anti-inflammatory effects, followed by ATP and melatonin. Histopathological examination confirmed most severe axonal degeneration, interstitial edema and Schwann cell proliferation in the amiodarone group, with substantial amelioration in the TPP-treated rats. Conclusions: Amiodarone induces neuropathic pain through oxidative and inflammatory injury to peripheral nerves. TPP exhibited superior neuroprotective efficacy compared with ATP and melatonin, highlighting its potential as a candidate therapeutic agent for amiodarone-related neuropathy. Further clinical research is warranted to support translational application of these findings.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Protective Effect of Exogenous Adenosine Triphosphate Against Ocular Toxicity of Linezolid in Rats
Esenulku, Cenap Mahmut; Cicek, Ibrahim; Somuncu, Ahmet Mehmet; Yavuzer, Bulent; Sezgin, Esra Tuba; Tastan, Tugba Bal; Yücel, Nurinisa; Karatas, Ezgi; Suleyman, Halis
Linezolid, a synthetic antimicrobial agent, may induce oxidative damage in ocular tissues, particularly in the optic nerve. Adenosine triphosphate (ATP) is involved in the production of antioxidants that scavenge and neutralize reactive oxygen species. This study aims to evaluate the potential protective effect of exogenous ATP against linezolid-induced ocular damage in rats, in comparison with methylprednisolone. Wistar-type rats were divided into five groups as follows: healthy (HG), ATP-only (ATPG), linezolid-only (LZDG), ATP + linezolid (ATLDG), and methylprednisolone + linezolid groups (MPLDG). Oxidative stress markers, antioxidant biomarkers, and proinflammatory cytokines were analyzed in isolated ocular tissues. Optic nerve tissue was also evaluated histopathologically. Linezolid administration increased the oxidative stress marker MDA and the proinflammatory cytokine TNF-α, while decreasing antioxidant parameters such as tGSH, SOD and CAT in rat ocular tissues, compared to the healthy group. However, it did not significantly alter serum troponin I levels. Histopathological analysis revealed that linezolid induced oxidative damage and inflammation in optic nerve tissue, with marked glial alterations. ATP administration reduced linezolid-induced oxidative stress in ocular tissue, as indicated by decreased MDA levels. It also enhanced antioxidant defenses by increasing tGSH, SOD, and CAT levels. In addition, ATP lowered proinflammatory cytokine levels, thereby alleviating inflammation. These effects collectively contributed to the restoration of biochemical parameters toward normal levels. In addition, ATP mitigated linezolid-induced optic nerve damage and glial alterations. The critical role of ATP in reducing oxidative stress, restoring antioxidant balance, and suppressing inflammation may represent a promising therapeutic approach for linezolid-induced ocular toxicity.
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 Erişim2025Relationship Between the Duration of Intravenous Ketamine Anesthesia and Postoperative Oxidative Stress and Inflammatory Response in Rats
Ince, Ramazan; Ozgodek, Habip Burak; Kahramanlar, Agah Abdullah; Yucel, Nurinisa; Sarıgül, Cengiz; Suleyman, Halis
Surgical trauma triggers oxidative and inflammatory responses that contribute to postoperative complications. Although the antioxidant and anti-inflammatory effects of ketamine have been reported, the impact of anesthesia duration on these mechanisms remains unclear. Forty-two male Wistar rats were randomized into healthy control (HG), ketamine only (KET; 60 mg/kg, i.p.), or laparotomy plus ketamine with 0–4 additional ketamine doses at 20 min intervals (KET + L, KET + L1–L4). At 24 h, levels of MDA, tGSH, SOD, CAT, IL-1β, IL-6, TNF-α, adrenaline and noradrenaline were measured in tail-vein blood. One-way ANOVA with Tukey’s post hoc test was used. Laparotomy under single-dose ketamine increased MDA and pro-inflammatory cytokines and decreased tGSH, SOD, CAT, ADR, and NDR versus HG and KET (all p < 0.001). After laparotomy, repeated ketamine dosing produced graded decreases in MDA and cytokines and increases in tGSH, SOD, CAT, ADR, and NDR toward control levels; effects were most pronounced in KET + L4 (all p < 0.001). Ketamine alone did not differ significantly from HG. In rats, ketamine modulates postoperative biological stress in a duration-dependent manner; prolonging anesthesia reduces oxidative–inflammatory load and restores catecholaminergic tone. These findings strongly support revisiting dose–duration protocols and underscore the need for mechanistic and clinical 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 Erişim2025Investigation into the Effects of Tramadol, Citalopram, Tianeptine, and Their Combinations on Rat Brain Tissue
Ates, Irem; Isik, Bahar; Gozen, Fusun; Yazici, Gulce Naz; Gulaboglu, Mine; Mammadov, Renad; Huseynova, Gulbeniz; Altuner, Durdu; Suleyman, Halis
Background: Tramadol binds to opioid receptors and inhibits norepinephrine and serotonin reuptake, causing serotonin syndrome. Tianeptine stimulates serotonin reuptake and reduces serotonin levels. The aim of this study was to investigate whether tianeptine is effective against serotonin syndrome that may occur with serotoninergic drugs such as tramadol and citalopram. Methods: Rats were divided into eight groups (n = 6) that received tramadol (50 mg/kg), citalopram (10 mg/kg), or tianeptine (5 mg/kg) alone or a combination of tramadol + citalopram, tramadol + tianeptine, citalopram + tianeptine or tramadol + citalopram + tianeptine at the same doses administered to the stomach by oral gavage for 3 weeks. The healthy control group was given saline. Malondialdehyde, total glutathione, superoxide dismutase, and catalase levels were measured in removed brain tissues. The tissues were also examined histopathologically. Results: In the tramadol, tramadol + citalopram, and tramadol + citalopram + tianeptine groups, malondialdehyde levels were found to be higher compared to the control group, while glutathione, superoxide dismutase, and catalase levels were found to be lower. In other groups, values close to the control group were measured. Morphological degeneration was observed in neurons in the tramadol + citalopram group. The swelling of astrocytes and pericellular edema in oligodendrocytes were also observed. A significant population increase was noted in microglial cells. Blood vessels belonging to the tissue were observed to be severely dilated and congested. Histopathological damage was partially resolved in the group given tramadol + citalopram + tianeptine. Conclusions: The tramadol + citalopram combination caused severe oxidative stress in brain tissue. Tramadol alone caused mild damage in brain tissue, whereas tianeptine prevented the brain damage caused by tramadol.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Role of Oxidant and Proinflammatory Cytokines and the Effect of Leflunomide in the Pathogenesis of Ovarian IschemiaReperfusion Injury
Isaoglu, Unal; Uyar, Elif Esra; Sahin, Nurullah; Bulut, Seval; Mammadov, Renad; Yilmaz, Betul Kalkan; Gunay, Murat; Mendil, Ali Sefa; Suleyman, Halis
Background and Objective: Ischemia-reperfusion (IR) causes tissue damage by inducing oxidative stress and inflammation. In this study, the protective ability of leflunomide, which is reputed to have antioxidant and anti-inflammatory effects, against IR-induced ovarian damage in rats was researched. Materials and Methods: Twenty-four albino Wistar female rats were divided into 4 groups of six each: Healthy (HG), sham-operated (SOG),ovarian IR (OIR) and leflunomide+ovarian IR (LOIR).One hour beforethe IR procedure, the LOIRgroup received 10 mg/kg leflunomide orally. Ovaries of rats in OIR and LOIR groups were subjected to 3 hrs ischaemia and 6 hrs reperfusion. For six days, leflunomide were implemented once a day. On day seven, the animals were euthanized and their ovaries were collected. The tissues were examined biochemically and histopathologically. Results: Leflunomide treatment significantly suppressed IR-induced rise in malondialdehyde (MDA),Tumor Necrosis Factor-Alpha (TNF-) and Interleukin 6 (IL-6) and the decline in Total Glutathione (tGSH), superoxide dismutase (SOD) and catalase (CAT) (p<0.001). Severe stromal hemorrhage, edema and follicular hemorrhage were noted in the ovaries of the IR group. Leflunomide treatment significantly prevented IR-induced ovarian tissue damage (p<0.05). Conclusion: Leflunomide could protect the ovaries with antioxidant and anti-inflammatory activity in ovarian IR injury.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2024Effect of Sugammadex on Ischemia-Reperfusion-Induced Oxidative and Inflammatory Ovarian Damage in Rats: Biochemical and Histopathological Evaluation
Kadioglu, Berrin Goktug; Suleyman, Bahadir; Mammadov, Renad; Yavuzer, Bulent; Altuner, Durdu; Yazici, Gulce Naz; Gulaboglu, Mine; Suleyman, Halis
Background and Objective: Polymorphonuclear leukocytes (PMNLs) play an important role in the pathogenesis of oxidative ischemia-reperfusion (I/R) damage. There is information that sugammadex inhibits PMNL infiltration into organs and tissues undergoing I/R. Present study aimed to investigate the potential protective effect of sugammadex against I/R-induced ovarian damage in rats and to elucidate its mechanism of action. Materials and Methods: The 24 female albino Wistar-type rats were divided into four groups as follows: Sham operation (SG), ovarian I/R (IRG), sugammadex (4 mg/kg) +ovarian I/R (SIR-4) and sugammadex (8 mg/kg) +ovarian I/R (SIR-8). Sugammadex was administered intraperitoneally. The animals were subjected to 2 hrs of ischemia followed by 2 hrs of reperfusion. Results: Sugammadex significantly inhibited the increase in I/R-induced malondialdehyde and the decrease in total glutathione, superoxide dismutase and catalase levels in ovarian tissue at a dose of 8 mg/kg compared with the dose of 4 mg/kg. Moderate follicular degeneration, vascular congestion, necrosis, oedema and hemorrhage were observed in the sugammadex (4 mg/kg) group, which significantly reduced the increase in I/R-related PMNL infiltration in ovarian tissue. Only mild vascular congestion was observed in the ovarian tissue of the 8 mg/kg sugammadex group, which did not show PMNL infiltration. Conclusion: Histopathological findings show that sugammadex protects ovarian tissue from oxidative and inflammatory injury of the I/R by inhibiting PMNL infiltration. Results also suggest that an 8 mg/kg dose of sugammadex, which completely inhibits PMNL infiltration into ovarian tissue, may be more beneficial than the 4 mg/kg dose in the treatment of I/R-induced ovarian damage.
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 - ArticleYalnız künye2024Effect of Rutin on Cisplatin-Induced Oxidative Skeletal Muscle Damage in Rats
Yasar, Hasan; Cimen, Ferda Keskin; Suleyman, Halis; Kurt, Nezahat; Arslan, Yusuf Kemal
Background and Objective: Cisplatin is a drug used to treat cancer, but it causes oxidative damage to muscle tissue. Rutin has an antioxidant effect. The study aims to investigate the biochemical and histopathological effects of rutin on the oxidative damage of cisplatin in skeletal muscle tissue. Materials and Methods: Rats were divided into four groups: A control group (CG), an only cisplatin-administered group (CIS), a cisplatin and rutin 50 mg kg(-1)-administered group (R-50) and a cisplatin and rutin 100 mg kg(-1)-administered group (R-100). Analyses were performed from the hindlimb muscles of experimental animals. Analyses of malondialdehyde (MDA), Total Glutathione (tGSH), glutathione reductase (GSHRd), glutathione S-transferase (GST) and superoxide dismutase (SOD) were performed. Histopathologic examination was performed in all groups. The CG and the other groups were compared. Results: The CG and R-100 groups were similar in all biochemical examinations. A statistically significant difference was detected between the control group and the CIS and R-50 groups in all examinations. Histopathological examinations revealed oxidative damage of cisplatin in the CIS group and R-50 group. The findings in the R-100 group were similar to the control group. Conclusion: Cisplatin causes oxidative damage to skeletal muscle tissue. Rutin has the potential to prevent the formation of such oxidative damage.
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.
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 Erişim2024Protective effect of cinnamon extract against cobalt-induced multiple organ damage in rats
Isik, Bahar; Suleyman, Bahadir; Mammadov, Renad; Bulut, Seval; Yavuzer, Bulent; Altuner, Durdu; Coban, Taha Abdulkadir; Suleyman, Halis
Background: The role of oxidative stress and inflammation in cobalt (Co) toxicity has been the focus of previous studies. Cinnamon and its main components have been reported to have protective effects in various tissues with antioxidant and anti-inflammatory effects. Aims: In this study, the protective effect of cinnamon extract (CE) against possible Co-induced heart, kidney, and liver damage in rats was investigated biochemically. Methods: Eighteen albino Wistar-type male rats were categorized into three groups (n = 6 per group): control (CG), CoCL2-administered (CoCL2), and CE + CoCL2-administered (CE + Co) groups. The CE + CoCL2 group was administered CE (100 mg/kg), and the CoCL2 and CG groups were administered distilled water orally by gavage. One hour after the administration, Co (150 mg/kg) was administered orally to the CE + CoCL2 and CoCL2 groups. This procedure was repeated once daily for 7 days. Then, biochemical markers were studied in the excised heart, kidney, and liver tissues. Results: CoCL2 increased oxidants and proinflammatory cytokines and decreased antioxidants in heart, kidney, and liver tissues. Heart, kidney, and liver tissue were affected by Co damage. CE treatment suppressed the CoCL2-induced increase in oxidants and proinflammatory cytokines and decrease in antioxidants in heart, kidney, and liver tissues. CE treatment has been shown to attenuate cardiac damage by reducing serum troponin I (TpI) and creatine kinase-MB (CK-MB), renal damage by reducing creatinine and blood urea nitrogen (BUN), and liver damage by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Conclusion: Co induced the production of oxidants and proinflammatory parameters and antioxidant depletion in heart, kidney, and liver tissues of rats. Our experimental results show that CE protects heart, kidney, and liver tissues against oxidative and inflammatory changes induced by CoCLl2.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Pulmonary toxicity associated with high-dose favipiravir and treatment options: biochemical and histopathological evaluation; [Toxicidad pulmonar asociada a altas dosis de favipiravir y opciones de tratamiento: Evaluación bioquímica e histopatológica]
Elma, Bekir; Suleyman, Bahadir; Mammadov, Renad; Yavuzer, Bulent; Unver, Edhem; Altuner, Durdu; Coban, Taha A.; Mokhtare, Behzad; Suleyman, Halis
Favipiravir is a broad-spectrum antiviral drug that is a viral RNA-dependent RNA polymerase inhibitor. Favipiravir is used in high doses to treat COVID-19 but has a side effect on humans at high doses. The side effects of favipiravir have been associated with oxidative stress in the literature. In this trial, we investigated the biochemical and histopathological effects of lacidipine, thiamine pyrophosphate (TTP), and adenosine triphosphate (ATP), drugs with antioxidant properties, on the lung toxicity caused by high-dose favipiravir in rats. The rats were classified into five groups: healthy (HG), favipiravir alone (Fav), lacidipine+favipiravir (LFav), TPP+favipiravir (TFav), and ATP+favipiravir (AFav). Favipiravir (800 mg/kg) was administered twice daily for seven days. Laci-dipine (4 mg/kg), TPP (20 mg/kg), and ATP (25 mg/kg) were administered once daily for seven days. Oxidant (malondialdehyde), non-enzymatic (total glutathi-one), and enzymatic (superoxide dismutase and catalase) antioxidant levels were measured in the excised lung tissues. Furthermore, the tissues were histopatho-logically examined. The systemic administration of high doses of favipiravir in-creased oxidant levels and decreased antioxidant levels in the lung tissue of rats. In parallel, the histopathological examination of the lung tissue revealed the presence of severe mononuclear cell infiltrations in interstitial areas and pronounced lymphoid hyperplasia. Lacidipine exhibited superior efficacy in mit-igating oxidative stress and preventing the decline of antioxidants induced by favipiravir compared with TPP and ATP. Histopathologically, the lacidipine administration significantly reduced lung oxidative damage. TTP moderately reduced severe favipiravir-associated lung injury. However, ATP was ineffective against favipiravir-associated lung injury. Lacidipine offers more therapeutic benefits than TPP in treating oxidative lung injury caused by high doses of favipiravir.
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