Yarbağ, Abdulhekim; Bardaş Özkan, Ebru; Ulaş, Mustafa; Arslan, Yusuf Kemal

The study tests the efficacy of subconjunctival ranibizumab and bevacizumab treatments in determining the oxidant and antioxidant levels during alkali-induced corneal neovascularisation. The researchers assigned 24 New Zealand White rabbits into four different groups, which included a healthy control, an alkali-injured control, a BV-treated group, and an RN-treated group, with six rabbits per group. All animals received alkali injury treatment except for the HC group. The AC group received six doses of subconjunctival saline 24 h after their injury, while the BV group and RN group received one dose of 0.5 mg of their respective treatment. The researchers conducted 14-day assays on normal tissue, blood plasma, and erythrocytes to determine total antioxidant status and total oxidant status. The researchers performed biochemical assays for total antioxidant status TAS and total oxidant status TOS on samples that were collected after the 14-day observation period. The corneal TOS levels increased in all injured groups when matched against the HC group. The RN group showed the highest corneal TOS levels, but the difference between the RN and AC and BV groups did not reach statistical significance. The injured groups showed higher corneal TAS levels than HC (p = 0.002), but the AC, BV, and RN groups showed no differences. The injured groups showed a significant decrease in erythrocyte TAS compared with HC (p < 0.001), but the injured groups showed lower plasma TOS levels than HC (p < 0.001). The researchers found no other systemic differences between the groups that received anti-VEGF treatment. The study results show that alkali injury leads to both local and systemic changes in redox status. The two anti-VEGF agents caused numerical changes in corneal oxidative parameters, but these changes did not achieve statistical significance. The research requires further investigation to understand potential agent-related effects on corneal redox balance, which should take place in larger, more detailed studies.

Yavuz, Arzu; Uzel, Kemine; Sezgin, Esra Tuba; Kuzucu, Mehmet; Yılmaz, Nesrin; Yazici, Gülcenaz; Hendem, Engin; Süleyman, Halis

(1) Background: Erlotinib is a tyrosine kinase inhibitor (TKI) widely used in cancer therapy; however, its potential adverse effects on ovarian tissue have not been fully elucidated. The present study aimed to investigate erlotinib-induced ovarian injury and to evaluate the protective effects of adenosine triphosphate (ATP) and flunarizine, administered alone or in combination, using biochemical and histopathological analyses in a rat model. (2) Methods: Thirty female rats were randomly allocated into five groups (n = 6 per group): healthy control, erlotinib, ATP + erlotinib, flunarizine + erlotinib, and ATP + flunarizine + erlotinib. ATP (5 mg/kg, intraperitoneal) and flunarizine (5 mg/kg, oral gavage) were administered daily for two weeks, while erlotinib (5 mg/kg) was given orally every two days for two weeks. Ovarian tissues were collected for oxidative stress analysis and histopathological evaluation, and blood samples were obtained for the measurement of serum prolactin and AMH levels. (3) Results: Erlotinib administration resulted in significant oxidative stress and histopathological alterations in ovarian tissue, accompanied by a reduction in serum AMH levels, while prolactin levels remained unchanged. Treatment with ATP or flunarizine partially attenuated these alterations. (4) Conclusions: Combined ATP and flunarizine administration showed stronger protective effects, improving biochemical parameters and preserving ovarian histology, suggesting a protective role against erlotinib-induced ovarian injury.

Kilic, Adil Furkan; Sezgin, Esra Tuba; Huseynova, Gulbaniz; Sarigul, Cengiz; Ozkaraca, Mustafa; Gungor, Ali; Mammadov, Renad; Suleyman, Halis; Cimen, Orhan

Background: Immune checkpoint inhibitors (ICIs), particularly programmed death-ligand 1 (PD-L1) inhibitors such as atezolizumab, have significantly improved outcomes in cancer therapy. However, these agents may cause immune-related adverse effects, including nephrotoxicity associated with oxidative stress and cellular stress responses. This study aimed to investigate and comparatively evaluate the protective effects of adenosine triphosphate (ATP) and taxifolin against atezolizumab-induced renal tissue injury in rats. Methods: Animals were divided into four groups: healthy (HG), atezolizumab (ATZ), ATP + atezolizumab (ATAZ), and taxifolin + atezolizumab (TXAZ). ATP (4 mg/kg, i.p.) and taxifolin (50 mg/kg, oral) were administered for six days, while atezolizumab (10 mg/kg, i.p.) was given on days 1 and 4. On day 7, renal tissues were collected for biochemical, histopathological, and double immunofluorescence analyses. Results: Atezolizumab significantly increased malondialdehyde (MDA) levels and decreased total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) levels, indicating enhanced oxidative stress and impaired antioxidant defense. These changes were accompanied by tubular degeneration and increased expression of apoptotic markers. Both ATP and taxifolin significantly ameliorated these alterations; however, ATP demonstrated a more pronounced protective effect. Conclusions: In conclusion, ATP and taxifolin attenuated the biochemical, histopathological, and immunofluorescence alterations associated with atezolizumab administration. ATP exhibited a more pronounced protective effect than taxifolin under the conditions of this experimental model. Nevertheless, further experimental studies are required to elucidate the mechanisms underlying these effects.

Uyar, Elif Esra; Yavuzer, Bulent; Babayeva, Mansura; Yucel, Nurinisa; Gunay, Murat; Suleyman, Halis

Background: The reproductive toxicity of first-line antituberculosis drugs remains poorly understood, particularly when used in combination. Rifampicin, isoniazid, pyrazinamide, and ethambutol are essential in tuberculosis therapy, but their potential influence on female fertility is uncertain. This pilot study evaluated their effects, given alone or in dual, triple, and quadruple combinations, on oxidative stress, endocrine markers, and reproductive outcomes in healthy female rats. Materials and Methods: Ninety-six albino Wistar-type female rats were divided into sixteen groups of six animals each and treated with single, dual, triple, or quadruple regimens of first-line antituberculosis drugs for 28 days. After treatment, two sexually mature males were introduced per group, and therapy continued for seven additional days. Serum malondialdehyde (MDA), total glutathione (tGSH), prolactin, and anti-Mullerian hormone (AMH) levels were measured, and fertility outcomes were evaluated. Results: In single-drug groups, MDA increased and tGSH decreased, but detectable infertility was not recorded. Prolactin remained stable except in the pyrazinamide group, where it declined. Dual-drug regimens increased oxidative imbalance; fertility failure occurred only in pyrazinamide-lacking groups and was accompanied by higher prolactin and lower AMH. Triple and quadruple combinations produced prominent oxidative imbalance. In triple-drug regimens, infertility was lower in pyrazinamide-containing groups than in the pyrazinamide-free group, but this pattern was not maintained in the quadruple regimen. Fertility impairment was not consistently aligned with the degree of oxidative stress and may involve prolactin and AMH alterations. Conclusions: These findings suggest that reproductive impairment under these experimental conditions may involve endocrine alterations and cannot be explained solely by serum oxidative imbalance. Pyrazinamide-associated fertility preservation appeared context-dependent and requires further confirmation in larger mechanistic studies with broader reproductive and endocrine assessment.

Emir, Izzet; Yavuzer, Bulent; Suleyman, Bahadir; Sarigul, Cengiz; Mendil, Ali Sefa; Sezgin, Esra Tuba; Altuner, Durdu; Gursul, Cebrail; Suleyman, Halis

Background: Hydroxychloroquine (HCQ), widely used in autoimmune and inflammatory diseases, has been associated with cardiotoxicity driven by oxidative, mitochondrial, and metabolic disturbances. However, no comparative evidence exists regarding whether thiamine, thiamine pyrophosphate (TPP), or their combination (TTPC) can mitigate HCQ-induced myocardial injury. Objective: This study examined the biochemical and histopathological effects of thiamine, TPP, and their combination in a rat model of HCQ-induced cardiomyopathy. Methods: Thirty male Wistar rats were assigned to five groups: healthy control, HCQ, thiamine + HCQ, TPP + HCQ, and TTPC + HCQ. Thiamine (20 mg/kg, intraperitoneal), TPP (20 mg/kg, intraperitoneal), or TTPC (20 mg/kg each, intraperitoneal) was administered once daily, followed by HCQ (120 mg/kg, oral, twice daily). After seven days, cardiac tissue was analyzed for MDA, tGSH, SOD, and CAT, while serum TnI, lactate, and LDH were measured from tail-vein blood samples. Cardiac samples underwent histopathological examination. Results: HCQ exposure markedly increased MDA, TnI, LDH, and lactate levels while reducing tGSH, SOD, and CAT, indicating severe oxidative and metabolic insult. Thiamine co-treatment failed to ameliorate these disturbances. Conversely, TPP restored redox balance, attenuated biomarker elevations, and improved cardiac biochemical profiles. TTPC produced comparable improvements but did not exceed those of TPP alone. Histopathologically, HCQ caused pronounced myocyte degeneration and mononuclear infiltration, whereas TPP and TTPC groups showed only mild inflammatory changes with preserved myocardial architecture. Conclusions: HCQ induces a marked redox imbalance accompanied by well-defined histopathological myocardial degeneration. TPP afforded robust cardio-protection, whereas thiamine offered no meaningful benefit. Collectively, these findings position TPP as a biologically plausible, clinically relevant candidate for mitigating HCQ-induced cardiomyopathy.

Akcan, İbrahim Orkun; Şenyurt, Sultan; Altuğ, Tolga; Ateş, Betül; Acar, Şeyma Tuba; Yücelsoy, Büşra; Kızılörs, Gizem; Taber, Christopher B.; Küçük, Hamza; Aydın, Ahmet Serhat

The purpose of this study was to examine associations between lower-limb mechanical strength, phase-oriented composite strength indices, generalized neuromuscular activation, and maximal soccer ball kicking speed in trained athletes. Twenty-five male soccer players (age: 20.64 ± 2.50 years; height: 179.28 ± 4.27 cm; body mass: 75.80 ± 9.41 kg) participated in this cross-sectional study. Isometric ankle and knee joint torques were assessed using an isokinetic dynamometer, and joint-specific and phase-oriented cross-joint composite indices were computed to represent integrated strength capacity across the kinetic chain. Neuromuscular activation was evaluated via surface electromyography during a standardized squat jump task. Ball-kicking speed was measured using Doppler radar during maximal instep kicks. Associations were analyzed using Pearson correlation coefficients (p ≤ 0.05) with false discovery rate correction for multiple comparisons. In unadjusted analyses, moderate positive correlations were observed for several ankle torque variables and composite ankle strength indices, while swing-phase composite measures demonstrated moderate correlations (r = 0.43–0.55). Knee strength indices and sEMG variables showed no significant relationships. However, none of the variables remained statistically significant after FDR correction, suggesting limited independent explanatory value of isolated isometric strength and non-task-specific neuromuscular activation assessed during a standardized squat jump for maximal kicking performance.

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.

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.

Cankaya, Muhammed Safa; Pala, Omer Osman

Background: Various treatment modalities have been employed for mechanical low back pain (MLBP), but evidence of their efficacy varies greatly. Objectıve: This randomized controlled trial aimed to assess the outcomes of Mulligan concept applications, including sustained natural apophyseal glides (SNAGS) and natural apophyseal glides (NAGS), in obese patients with MLBP. Methods: The study, conducted between January 2021 and June 2022 at a tertiary hospital, involved randomizing patients into two groups. Both groups underwent six sessions of stretching and strengthening exercises every other day. The Mulligan group received additional intervention with SNAG and NAGS techniques. Measurements were made regarding the Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI) score and range of motion (ROM) for the patients’ MLBP level. Results: Post-interventions, both groups exhibited positive changes in flexion ROM, extension ROM, right and left rotation ROM, right and left lateral flexion ROM, VAS score, and ODI score compared to pre-intervention (p < 0.001 for both groups and variables). The Mulligan group showed a higher increase in ROM and a more significant decrease in VAS and ODI scores. Conclusıons: Mulligan mobilization techniques prove significantly beneficial for enhancing ROM in all directions, reducing pain levels, and alleviating disability in obese individuals with MLBP.

Ozden, Eda Mehtap; Bingol, Zeynebe; Mutlu, Muzaffer; Karagecili, Hasan; Köksal, Ekrem; Goren, Ahmet C.; Alwasel, Saleh H.; Gulcin, İlhami

Determining the antioxidant abilities and enzyme inhibition profiles of medicinally important plants and their oils is of great importance for a healthy life and the treatment of some common global diseases. Kiwifruit (Actinidia deliciosa) oil was examined and researched using several bioanalytical methods comprehensively for the first time in this research to determine its antioxidant, antiglaucoma, antidiabetic and anti-Alzheimer’s capabilities. Additionally, the kiwifruit oil inhibitory effects on acetylcholinesterase (AChE), carbonic anhydrase II (CA II), and α-amylase, which are linked to a number of metabolic illnesses, were established. Furthermore, LC-HRMS analysis was used to assess the phenolic content of kiwifruit oil. It came to light that kiwifruit oil contained 26 different phenolic compounds. According to the LC-HRMS findings, kiwifruit oil is abundant in apigenin (74.24 mg/L oil), epigallocatechin (12.89 mg/L oil), caryophyllene oxide (12.89 mg/L oil), and luteolin (5.49 mg/L oil). In addition, GC-MS and GC-FID studies were used to ascertain the quantity and chemical composition of the essential oils contained in kiwifruit oil. Squalene (53.04%), linoleoyl chloride (20.28%), linoleic acid (2.67%), and palmitic acid (1.54%) were the most abundant compounds in kiwifruit oil. For radical scavenging activities of kiwifruit oil, 1,1-diphenyl-2-picryl-hydrazil (DPPH•) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS•+) radicals scavenging techniques were examined. These methods effectively demonstrated the potent radical scavenging properties of kiwifruit oil (IC50: 48.55 μg/mL for DPPH•, and IC50: 77.00 μg/mL for ABTS•+ scavenging). Also, for reducing capabilities, iron (Fe3+), copper (Cu2+), and Fe3+-2,4,6-tri(2-pyridyl)-S-triazine (TPTZ) reducing abilities were studied. Moreover, kiwifruit oil showed a considerable inhibition effect towards hCA II (IC50: 505.83 μg/mL), AChE (IC50: 12.80 μg/mL), and α-amylase (IC50: 421.02 μg/mL). The results revealed that the use of kiwifruit oil in a pharmaceutical procedure has very important effects due to its antioxidant, anti-Alzheimer, antidiabetic, and antiglaucoma effects.