Browsing by Author "Yildizhan, Kenan"

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Alpha-Lipoic Acid Preserves Testicular Integrity Under 2.45 GHz Electromagnetic Radiation by Restoring Redox and Inflammatory Balance
(MDPI, 2025) Cakir, Tahir; Keskin, Seda; Yildizhan, Kenan; Bayir, Mehmet Hafit; Altindag, Fikret; Karaman, Erbil
Background/Objective: Electromagnetic radiation (EMR) from wireless technologies has raised concerns about male reproductive health. We aimed to evaluate the protective role of alpha-lipoic acid (ALA), a potent antioxidant, against testicular alterations induced by 2.45 GHz EMR. Methods: Twenty-eight adult male rats were randomly divided into four groups: control, EMR, ALA, and ALA+EMR. Animals in the EMR and ALA+EMR groups were exposed to EMR for 2 h/day for 1 month. Testicular tissues were examined histologically, stereologically, and immunohistochemically, while serum samples were analysed biochemically. Results: EMR exposure caused marked structural damage, including disruption of seminiferous tubule architecture, increased collagen deposition, and expansion of tubular and interstitial volumes. These pathological changes were primarily prevented in the ALA+EMR group. Immunohistochemical analyses revealed increased IL-6 and TNF-alpha expression following EMR exposure, whereas ALA supplementation significantly reduced these inflammatory markers and restored AR, ZO-1, and ZO-2 expression. Biochemically, EMR reduced antioxidant enzyme activities (SOD, GSH, GPx) and elevated MDA levels, indicating oxidative stress; these parameters were reversed by ALA treatment. Conclusions: Collectively, our findings demonstrate that 2.45 GHz EMR induces oxidative stress, inflammation, and testicular injury, while ALA provides significant protection. These results highlight the therapeutic potential of ALA as a protective agent against EMR-related reproductive toxicity and infertility risk.
Antitumor Activity of Urtica Dioica Seed Extract on Diethylnitrosamine-Induced Liver Carcinogenesis in Rats
(Natl inst Science Communication-niscair, 2024) Keles, Omer Faruk; Huyut, Zubeyir; Arslan, Mevlut; Yildizhan, Kenan; Yener, Zabit
Hepatocellular carcinoma (HCC) is a significant health problem for human life; therefore, new therapeutic approaches are essential. In vitro studies have shown that the extract of Urtica dioica seed extract (UDSE) may be a crucial protective agent to prevent HCC. Therefore, this study aimed to investigate the antitumor efficacy of UDSE in the process of carcinogenesis induced by diethylnitrosamine (DENA). The antitumor efficacy was evaluated by examining liver tissue histopathology and expression of Hep par-1, alpha-fetoprotein (AFP), caspase-3, and inducible nitric oxide synthase (iNOS) in the liver tissue and activities/levels of aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), carbohydrate antigen (CA) 15-3, CA 19-9, CA 125-II in the serum, and also total oxidative stress (TOS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), total antioxidant status (TAS) in the serum and liver. In addition, real-time PCR was used to evaluate the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL-1 beta, IL-6), and proliferating cell nuclear antigen (PCNA) in liver tissue. It was observed that DENA application increased liver function tests, cancer markers, apoptosis, and proinflammatory cytokine levels, but UDSE application and DENA suppressed these increases. The findings and histopathological data demonstrated that the UDSE has a very significant antitumor efficacy on the process of DENA-induced hepatocellular carcinogenesis, which appears to be attributable to its antioxidant, anti-apoptotic, and anti-proliferative activity.
Curcumin Protects Against Mpp+-Induced Neurotoxicity in Sh-Sy5y Cells by Modulating the Trpv4 Channel
(Springer, 2025) Cinar, Ramazan; Yildizhan, Kenan
BackgroundIt is well acknowledged that neuroinflammation, mitochondrial dysfunction, and oxidative stress (OS) play a role in the etiology of Parkinson's disease (PD). Curcumin (CUR) protect neuronal cells by interfering with the production of reactive oxygen species (ROS) in neuronal cells and suppressing OS. In this study, we investigated the role of the TRPV4 channel under CUR stimulation in the PD model induced by MPP+ in SH-SY5Y cells. MethodsThe cells were divided into four groups: control, CUR, MPP+ and MPP++CUR. In addition, incubations were performed with TRPV4 channel agonist GSK1016790A (GSK) and its antagonist Ruthenium red (Rr) to follow the Ca2+ current induced through the TRPV4 channel. ResultsMPP+ exposure increased mitochondrial and intracellular ROS production and mitochondrial membrane potential in the cell, while decreasing GSH levels. During CUR and Rr incubation, MPP+ exposure and TRPV4 agonist GSK-induced TRPV4 overstimulation were down-regulated. The effects of MPP+ on intracellular damage were changed by CUR treatment, as seen in changes in GSH levels, mROS, iROS, JC/1, apoptosis, and TRPV4 expression value compared to the MPP+ group. ConclusionsThe CUR treatment in the in vitro PD model created with MPP+ reduced cellular damage by regulating mitochondrial dysfunction, OS and TRPV4 channel activation in MPP+-induced neurotoxicity with the antioxidant properties of CUR.
Effect of Abemaciclib and Curcumin Administration on Sex Hormones, Reproductive Functions, and Oxidative Dna Expression in Rats
(Taylor & Francis Ltd, 2024) Huyut, Zuebeyir; Ucar, Bunyamin; Yildizhan, Kenan; Altindag, Fikret; Huyut, Mehmet Tahir
This study investigated whether abemaciclib (ABE) administration had any adverse effects on ovarian and sex hormones in female rats, and the protective effect of curcumin. Forty female rats were equally divided into the sham control, DMSO, curcumin (CMN), ABE, and ABE+CMN groups. Pharmaceuticals were administered by gavage daily for 28 days. Serum sex hormones were measured in an autoanalyzer operating with a microparticle immunoassay method. In addition, histopathological examination and 8-OHdG expression were performed on the ovarian tissue. Progesterone and testosterone levels were significantly decreased, while estradiol levels were significantly increased, in the ABE group compared to the sham and DMSO groups. In addition, there were significant differences in sex hormone levels in the CMN and/or CMN+ABE groups compared to the ABE group. There was decreased expression of 8-OHdG in the ABE+CMN group compared to the ABE or CMN only groups. This study exhibited that ABE administration can adversely affect functions and histology of the ovarian tissue, but CMN therapy may be protective against the adverse effects on ovarian in ABE-induced rats.
Effect of Curcumin on Lipid Profile, Fibrosis, and Apoptosis in Liver Tissue in Abemaciclib-Administered Rats
(Taylor & Francis Ltd, 2023) Huyut, Zubeyir; Ucar, Bunyamin; Altindag, Fikret; Yildizhan, Kenan; Huyut, Mehmet Tahir
Abemaciclib (ABEM) is an important antitumor agent for breast cancer treatment. However, the side-effects of ABEM are unclear in the liver. This study investigated the protective effect of curcumin (CURC) on liver damage caused by ABEM. The rats were divided into five groups with eight animals in each group; Control, DMSO (150 mu L for per rats), CURC, 30 mg/kg/day), ABE (26 mg/kg/day), and ABE + CURC (26 mg/kg/day ABE, 30 mg/kg/day) groups. Injections were administered daily for 28 days. The levels of AST, LDH, HDL, LDL, triglyceride, and total cholesterol in serum, and hepatic tissue fibrosis, caspase-3, Bax, and TNF-alpha expression were higher in the ABE group compared to the control group (p < 0.05). Also, these parameters in the ABEM + CURC group were lower than in the ABE group (p < 0.05). The results showed that ABE administration could cause liver damage and increase fibrosis in the liver. In addition, it was shown that co-administration of CURC with ABE could suppress the levels of AST, LDH, HDL, LDL, triglyceride, and total cholesterol in serum, and fibrosis, caspase-3, Bax, and TNF-alpha expressions in the liver. These data are the first in the literature. Therefore, the administration of CURC following ABE may be a therapeutic agent in preventing liver damage.
Effect of Hesperidin on Lipid Profile, Inflammation and Apoptosis in Experimental Diabetes
(Maik Nauka/interperiodica/springer, 2025) Yildizhan, Kenan; Bayir, Mehmet Hafit; Huyut, Zuebeyir; Altindag, Fikret
In recent years, therapeutic approaches against diabetes-induced liver damage have attracted great interest. Studies indicate the anticarcinogenic, anti-inflammatory, antioxidant, and lipid-lowering potential of hesperidin (HESP), a flavonoid in citrus fruits. This study examined how HESP prevented streptozotocin (STZ)-induced diabetic liver damage. Four groups of seven rats each were created: Control, HESP (100 mg/kg/day), STZ (45 mg/kg), and STZ + HESP (45 mg/kg and 100 mg/kg/day, respectively). Serum AST, ALT, LDH, LDL, triglyceride, total cholesterol levels, and the TNF-alpha, IL-1 beta, and caspase-3 expression levels of liver tissue in the STZ group were higher than the other groups (p < 0.05). However, these values were significantly lower (p < 0.05) in the STZ + HESP group compared to the STZ group. Furthermore, administering HESP together with STZ reduced liver expression levels of caspase-3, TNF-alpha, and IL-1 beta, as well as blood levels of AST, ALT, LDH, LDL, triglyceride, and total cholesterol. HESP against diabetes-induced hepatic damage reduced proinflammatory cytokine levels, and returned the lipid profile, and apoptotic indicators to normal levels. These findings suggested that HESP therapy may be an important therapeutic role against diabetes-induced liver damage.
Effect of Hesperidin on Sciatic Nerve Damage in Stz-Induced Diabetic Neuropathy: Modulation of Trpm2 Channel
(Springer, 2023) Bayir, Mehmet Hafit; Yildizhan, Kenan; Altindag, Fikret
Diabetic neuropathy (DNP) is a severe complication of diabetes mellitus. In this study, we examined the potential of hesperidin (HES) to attenuate DNP and the involvement of the TRPM2 channel in this process. The rats were given a single dose of 45 mg/kg of streptozotocin (STZ) intraperitoneally to induce diabetic neuropathic pain. On the third day, we confirmed the development of diabetes in the DNP and DNP + HES groups. The HES groups were treated with 100 mg/kg and intragastric gavage daily for 14 days. The results showed that treatment with HES in diabetic rats decreased STZ-induced hyperglycemia and thermal hyperalgesia. Furthermore, in the histopathological examination of the sciatic nerve, HES treatment reduced STZ-induced damage. The immunohistochemical analysis also determined that STZ-induced increased TRPM2 channel, type-4 collagen, and fibrinogen immunoactivity decreased with HES treatment. In addition, we investigated the TRPM2 channel activation in the sciatic nerve damage mechanism of DNP model rats created by STZ application using the ELISA method. We determined the regulatory effect of HES on increased ROS, and PARP1 and TRPM2 channel activation in the sciatic nerves of DNP model rats. These findings indicated that hesperidin treatment could attenuate diabetes-induced DNP by reducing TRPM2 channel activation.
The Effect of Selenium Against Cadmium-Induced Nephrotoxicity in Rats: The Role of the Trpm2 Channel
(Mdpi, 2025) Keles, Omer Faruk; Bayir, Mehmet Hafit; Cicek, Haci Ahmet; Ahlatci, Adem; Yildizhan, Kenan
This study investigated the protective effect of selenium (Se) in a cadmium (Cd)-induced nephrotoxicity model in rats and the role of the TRPM2 channel in this mechanism. For this purpose, Cd (25 mg/kg orally), Se (0.5 mg/kg i.p.), and 2-aminoethoxydiphenyl borate (2-APB), a TRPM2 channel antagonist, (3 mg/kg i.p.) were administered to rats every day for 5 days. At the end of the study, kidney tissues were analysed using histological and biochemical methods. A histopathological examination revealed congestion, tubular degeneration, necrosis, and glomerular adhesion in the Cd group. However, these lesions were significantly reduced in the Cd + Se and Cd + 2-APB groups, while the Cd + Se + 2-APB group showed a histological appearance similar to the control group. Immunohistochemical analysis revealed that Caspase-3, Bax, and TRPM2 expression was higher in the Cd group, while these levels were lower in the Se and 2-APB treatment groups (p < 0.05). Among the groups that received Cd, urea, creatinine, TOS, TNF-alpha, and IL-1 beta levels were at the highest level in the Cd group, while TAS level was at the lowest level (p < 0.05). The Se and 2-APB treatment modulated these parameters; however, Se + 2-APB treatment reduced urea, creatinine, TOS, TNF-alpha, and IL-1 beta levels to the lowest level compared to the Cd groups and brought the TAS level closer to the control group (p < 0.05). These findings indicated that targeting TRPM2 channel inactivation together with the selenium treatment could alleviate Cd-induced nephrotoxicity.
Effect of Selenium Against Doxorubicin-Induced Oxidative Stress, Inflammation, and Apoptosis in the Brain of Rats: Role of Trpm2 Channel
(Natl inst Science Communication-niscair, 2023) Yildizhan, Kenan; Huyut, Zuebeyir; Altindag, Fikret; Ahlatci, Adem
Doxorubicin (DOX) is widely used as an anticancer drug in humans' various solid and haematological tumours. Although many studies on the toxic effect of DOX are used in different organs, its impact on brain tissue has yet to be adequately studied. This study investigated the protective effect of selenium (Se) and the role of transient receptor potential melastatin-2 (TRPM2) channel activation against brain damage caused by DOX administration. Sixty rats were randomly divided into the sham, dimethyl sulfoxide (DMSO), DOX, DOX + Se, DOX + N-(p-amylcinnamoyl) anthranilic acid (ACA), and DOX + Se + ACA groups. The reactive oxygen species (ROS), poly [ADP-ribose] polymerase 1 (PARP1), and TRPM2 channel levels in brain tissues were measured by ELISA. In addition, a histopathological examination was performed in the cerebral cortex and hippocampal areas, and the TRPM2 channel, NF-icB, and caspase-3 expression were determined immunohistochemically. The levels of ROS, PARP1 and TRPM2 channel in the DOX group were higher than in the sham and DMSO groups (P < 0.05). However, these parameters were decreased in the in DOX+Se and DOX+ACA groups by the treatments of Se and ACA (P < 0.05). Also, we determined that Se and ACA treatment decreased the NF-icB, caspase-3, and TRPM2 channel expression in the cerebral cortex and hippocampal areas in the DOX-induced rats. The data showed that Se and/or ACA administration together with DOX administration could be used as a protective agent against DOX-induced brain damage.
The Effects of Berberine and Curcumin on Cardiac, Lipid Profile and Fibrosis Markers in Cyclophosphamide-Induced Cardiac Damage: The Role of the Trpm2 Channel
(Wiley, 2024) Huyut, Zuebeyir; Yildizhan, Kenan; Altindag, Fikret
Cyclophosphamide (CYP) is widely used to treat various types of cancer. In addition to the therapeutic properties of this drug, unfortunately, its side effects are still not fully understood. This study investigated the protective effect of curcumin (CURC) and berberine (BER) on CYP-induced cardiac damage. Thirty-six male rats were equally divided into the control, dimethyl sulfoxide (DMSO), CYP, CYP + CURC, CYP + BER and CYP + BER + CURC groups. Troponin-I, Creatine kinase-myocardial band (CK-MB), total cholesterol, triglyceride levels in serum samples, and reactive oxygen species (ROS), poly(ADP-ribose) polymerase-1 (PARP-1), and transient receptor potential melastatin 2 (TRPM2) channel levels in heart tissue were measured using an enzyme-linked immunoassay (ELISA) kit. In addition, histopathological examination and immunohistochemical investigation of the TRPM2 channel, fibroblast specific protein-1 (FSP1), transforming growth factor-beta- 1 (TGF-beta 1) and alpha-smooth muscle actin (alpha-SMA) expressions were determined in heart tissue. The CYP group's troponin-I, total cholesterol, triglyceride, CK-MB, ROS, PARP-1 and TRPM2 channel levels were higher than in the other groups in the ELISA measurements (p < 0.05). In contrast, these parameters in the group treated with CURC and BER together with CYP were lower than in the CYP group (p < 0.05). Additionally, CUR and BER reduced CYP-induced pathological damage, TRPM2, FSP1, TGF-beta 1 and alpha-SMA expressions. The data showed that CYP administration can cause cardiac damage by increasing the TRPM2 channel, TGF-beta 1, FSP1 and alpha-SMA expression levels. Therefore, we concluded that CURC and BER administration following CYP application may be used as therapeutic agents to prevent CYP-induced cardiac damage.
Hesperidin Alleviates Streptozotocin-Induced Cardiac Damage in Rats through Modulation Oxidative Stress, Inflammation and Apoptosis
(National Institute of Science Communication-NISCAIR, 2026) Yildizhan, Kenan; Bayir, Mehmet Hafit; Huyut, Zubeyir; Altindag, Fikret
This study investigated the potential cardioprotective effects of hesperidin (HES) against cardiac damage induced by streptozotocin (STZ)-mediated diabetes in rats. Diabetes was induced by a single intraperitoneal injection of STZ (45 mg/kg) and HES (100 mg/kg/day) were administered intragastrically to treatment groups for 14 days. Cardiac tissue samples were analyzed using the ELISA method for Total Antioxidant Status (TAS) Total Oxidant Status (TOS) malondialdehyde (MDA) and glutathione (GSH) levels, while inflammatory (TNF-alpha) and apoptotic (Caspase-3) markers were assessed immunohistochemically. STZ administration resulted in significantly increased TNF-alpha expression, TOS and MDA levels, and reduced TAS and GSH levels, accompanied by severe myocardial degeneration, necrosis, and vascular congestion. HES treatment markedly improved antioxidant status, decreased oxidative and inflammatory markers, and reduced apoptosis. Histopathological evaluations demonstrated substantial preservation of cardiac morphology in the STZ+HES group. Overall, these findings suggest that HES has a protective effect against diabetes-induced cardiac injury, likely through the modulation of oxidative stress, inflammation, and apoptosis.
Involvement of Trpm2 Channel on Doxorubicin-Induced Experimental Cardiotoxicity Model: Protective Role of Selenium
(Springernature, 2022) Yildizhan, Kenan; Huyut, Zubeyir; Altindag, Fikret
Doxorubicin (DOXR) is an important chemotherapeutic drug used in cancer treatment for many years. Several studies reported that the use of DOXR increased toxicity by causing an increase in oxidative stress (OS), especially in the heart. In this study, we investigated the protective effect of selenium (Se) and the role of transient receptor potential melastatin-2 (TRPM2) channel activation by using N-(p-amylcinnamoyl) anthranilic acid (ACA) in a model of DOXR-induced cardiotoxicity. Sixty female rats were equally divided into the control, dimethyl sulfoxide (DMSO), DOXR, DOXR + Se, DOXR + ACA, and DOXR + Se + ACA groups. Glutathione (GSH), glutathione peroxidase (GSH-Px), caspases (Cas) 3 and 9, interleukin 1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), reactive oxygen species (ROS), poly [ADP-ribose] polymerase 1 (PARP-1), and TRPM2 channel levels were measured by ELISA. In addition, histopathological examination was performed in cardiac tissues and TNF-alpha, caspase 3, and TRPM2 channel expression levels were determined immunohistochemically. The levels of GSH, GSH-Px, caspases 3 and 9, IL-1 beta, TNF-alpha, ROS, PARP-1, and TRPM2 channel in serum, and cardiac tissue in the DOXR group were higher than in the control and DMSO groups (p < 0.05). However, these parameters in Se and/or ACA treatment groups were lower than in the DOXR group (p < 0.05). Also, we determined that Se and/or ACA treatment together with DOXR application decreased the TNF-alpha, Cas-3, and TRPM2 channel expression levels in the cardiac tissue. The data showed that administration of Se and/or ACA treatment together with DOXR may be used as a therapeutic agent in preventing DOXR-induced cardiotoxicity.
Involvement of Trpm2 Channel on Doxorubicin-Induced Experimental Cardiotoxicity Model: Protective Role of Selenium (Vol 201, Pg 2458, 2023)
(Springernature, 2023) Yildizhan, Kenan; Huyut, Zubeyir; Altindag, Fikret
The Involvement of Trpm2 on the Mpp+-Induced Oxidative Neurotoxicity and Apoptosis in Hippocampal Neurons From Neonatal Mice: Protective Role of Resveratrol
(Taylor & Francis Ltd, 2022) Yildizhan, Kenan; Cinar, Ramazan; Naziroglu, Mustafa
Parkinson's disease (PD) is an age-related chronic neurodegenerative disease. Although PD is known to be a result of damage to hippocampal neurons, its molecular mechanism has yet to be completely clarified. The neurodegeneration in hippocampal neurons has been suggested to include excessive production of reactive oxygen species (ROS). Mitochondrial dysfunction and disruption of intracellular Ca2+ homeostasis play the most important role in the increase in ROS production for the cells. Remarkably, it is stated in the literature that especially the change of Ca2+ homeostasis triggers neuronal degeneration. TRPM2 is a unique calcium-permeable nonselective cation channel, and densest in the numberless neuronal population. The current study aims to elucidate the effect of antioxidant resveratrol (Resv) on TRPM2-mediated oxidative stress (OS) induced by 1-methyl-4-phenylpyridinium (MPP) exposure in the primary mouse hippocampal neurons. The neurons were divided into four groups as Control, Resv , MPP, and MPP+ Resv. In the current results, the activation of TRPM2 was observed in primary hippocampal neurons with MPP incubation. TRPM2 channel expression levels in the MPP group increased in hippocampal neurons after MPP exposure. In addition, intracellular free Ca2+ concentration and TRPM2 channel currents were highest in MPP groups, although they were decreased by the Resv treatment. In addition, mitochondrial membrane depolarization, ROS, caspase-3, caspase-9, and apoptosis values induced by MPP decreased with resveratrol treatment. In conclusion, in our study, we observed that the dysregulation of OS-induced TRPM2 channel activation in hippocampal neurons exposed to MPP caused apoptotic cell death in neurons, while the use of resveratrol had a protective effect by reducing OS resources in the environment.
Nmda Receptor Activation Stimulates Hypoxia-Induced Trpm2 Channel Activation, Mitochondrial Oxidative Stress, and Apoptosis in Neuronal Cell Line: Modular Role of Memantine
(Elsevier, 2023) Yildizhan, Kenan; Naziroglu, Mustafa
TRPM2 channel is activated by the increase of hypoxia (HYP)-mediated excessive mitochondrial (mROS) and cytosolic (cROS) free reactive oxygen species generation and intracellular free Ca2+ ([Ca2+]i) influx. The stimulations of the N-methyl-D-aspartate (NMDA) receptor and TRPM2 channel induce mROS and apoptosis in the neurons, although their inhibitions via the treatments of memantine (MEM) and MK-801 decrease mROS and apoptosis. However, the molecular mechanisms underlying MEM treatment and NMDA inhibition' neuroprotection via TRPM2 inhibition in the HYP remain elusive. We investigated the modulator role of MEM and NMDA via the modulation of TRPM2 on oxidative neurodegeneration and apoptosis in SH-SY5Y neuronal cells. Six groups were induced in the SH-SY5Y and HEK293 cells as follows: Control, MEM, NMDA blocker (MK-801), HYP (CoCl2), HYP + MEM, and HYP + MK-801. The HYP caused to the increases of TRPM2 and PARP-1 expressions, and TRPM2 agonist (H2O2 and ADP-ribose)-induced TRPM2 current density and [Ca2+]i concentration via the upregulation of mitochondrial membrane potential, cROS, and mROS generations. The alterations were not observed in the absence of TRPM2 in the HEK293 cells. The increase of cROS, mROS, lipid peroxidation, cell death (propidium iodide/Hoechst) rate, apoptosis, caspase -3, caspase -8, and caspase -9 were restored via upregulation of glutathione and glutathione peroxidase by the treatments of TRPM2 antagonists (ACA or 2-APB), MEM, and MK-801. In conclusion, the inhibition of NMDA receptor via MEM treatment modulated HYPmediated mROS, apoptosis, and TRPM2-induced excessive [Ca2+]i and may provide an avenue for protecting HYP-mediated neurodegenerative diseases associated with the increase of mROS, [Ca2+]i, and apoptosis.
The Protective Effect of Curcumin on Cardiac Markers and Fibrosis in Abemaciclib-Induced Cardiac Damage in Rats
(Wiley, 2023) Huyut, Zubeyir; Ucar, Bunyamin; Yildizhan, Kenan; Altindag, Fikret
Abemaciclib (ABE) is a cyclin-dependent kinase inhibitor used in combination with an antiestrogen in the treatment of breast cancer. In addition to the important therapeutic properties of this drug, its side effects are not fully known. In this study, we aimed to investigate the protective effect of curcumin (CUR) on cardiac damage caused by ABE administration. Forty rats were equally divided into control, dimethyl sulfoxide (150 mu L), CUR (30 mg/kg/day), ABE (26 mg/kg/day), and ABE + CUR (26 mg/kg/day ABE and 30mg/kg/day CUR) groups (n = 8). Injections were administered daily for 28 days. Troponin-I, total cholesterol, and creatine kinase myocardial band (CK-MB) levels and cardiac fibrosis were higher in the ABE group than in the control group (p < 0.05), and were lower in the ABE + CUR group than in the ABE group (p < 0.05). The results showed that ABE administration can cause cardiac damage and increase cardiac fibrosis. However, they showed that coadministration of CUR with ABE could suppress increases in CK-MB, troponin-I, and total cholesterol levels and also cardiac fibrosis associated with cardiac damage. Therefore, we can infer that the subsequent administration of CUR ABE treatment can be used as a therapeutic strategy for preventing cardiac damage.
Protective Effects of Urtica Dioica L. Seed Extract on Liver Tissue Injury and Antioxidant Capacity in Irradiated Rats
(Univ Sao Paulo, Conjunto Quimicas, 2020) Yildizhan, Kenan; Demirtas, Omer Can; Uyar, Ahmet; Huyut, Zubeyir; Cakir, Tahir; Keles, Omer Faruk; Yener, Zabit
Radiotherapy is often used for the treatment of cancer. However, it causes some side effects in patients. This study aimed to determine the hepatoprotective effects of Urtica dioica L. seed-extract (UDSE) in radiation-induced liver injury. Thirty-two male rats were randomly divided into 4 groups (n=8): control(C) group: no action was taken; radiation (R) group: irradiation was administrated at 5Gy single-fraction, radiation with UDSE(R+UDSE) group: irradiation was administrated at 5 Gy single-fraction and animals were fed pellets with 30 mL UDSE/kg; UDSE group: animals were fed pellets with 30 mL UDSE/kg. All of the experiments were performed in all of the groups over 10 days. Malondialdehyde (MDA) and reduced-glutathione (GSH) levels and superoxide-dismutase (SOD), catalase (CAT), glutathione-peroxidase (GSH-Px), aspartate-transaminase (AST), and alanine-aminotransferase (ALT) activities were detennined. Histopathological findings were also evaluated in liver tissues. SOD, CAT and GSH-Px activities and GSH levels in the serum and liver were significantly increased, while MDA levels decreased in the R+UDSE group compared with the R group (P<0.05). Moreover, AST and ALT serum activities in the R+UDSE group were lower than those in the R group (P<0.05). In addition, radiation induced degenerative/necrotic changes in the R group were significantly compensated in the R+UDSE group. The results showed that radiation increased oxidative stress and decreased antioxidant capacity, as well as degeneration in the liver. However, UDSE attenuated these degenerative changes.
Protective Role of Selenium on Mpp+ and Homocysteine-Induced Trpm2 Channel Activation in Sh-Sy5y Cells
(Taylor & Francis Ltd, 2022) Yildizhan, Kenan; Naziroglu, Mustafa
Homocysteine is an intermediate product of biochemical reactions occurring in living organisms. It is known that drugs that increase dopamine synthesis used in Parkinson's disease (PD) cause an increase in the plasma homocysteine level. As the plasma homocysteine level increases, the amount of intracellular free calcium ion ([Ca2+](i)) and oxidative stress increase. As a result, it contributes to the excitotoxic effect by causing neurodegeneration. TRPM2 cation channel is activated by high [Ca2+](i) and oxidative stress. The role of TRPM2 in the development of neuronal damage due to the increase in homocysteine in PD has not yet been elucidated. In current study, we aimed to investigate the role of the TRPM2 and selenium (Se) in SH-SY5Y neuronal cells treated with homocysteine (HCT) and MPP . SH-SY5Y cells were divided into four groups: control, MPP, MPP + HCT, and MPP + HCT + Se. The results of plate reader assay, confocal microscope imaging, and western blot analyses indicated upregulation of apoptosis, [Ca2+](i), mitochondrial membrane depolarization, caspase activation, and intracellular ROS values in the cells. The MPP + HCT group had considerably higher values than the other groups. The MPP + HCT + Se group had significantly lower values than all the other groups except the control group. In addition, incubation of MPP + HCT and MPP + HCT + Se groups with TRPM2 antagonist 2-APB increased cell viability and reduced intracellular calcium influx and apoptosis levels. It is concluded that the activation of TRPM2 was propagated in HCT and MPP-induced SH-SY5Y cells by the increase of oxidative stress. The antioxidant property of Se regulated the TRPM2 channel activation and neurodegeneration by providing intracellular oxidant/antioxidant balance.
Protective Role of Zingerone Against High Glucose-Induced Retinal Pigment Epithelial Cell Damage Through Modulation of the Trpm2 Channel Pathway
(Springer, 2026) Cig, Esmanur; Yardimci, Mahmut; Cinar, Ramazan; Yildizhan, Kenan
Background Diabetic retinopathy (DRP) is a leading cause of vision loss associated with chronic hyperglycemia-induced oxidative stress (OS), inflammation, and mitochondrial dysfunction in retinal pigment epithelium (RPE) cells. Zingerone (ZGN), a phenolic compound derived from Zingiber officinale, exhibits potent antioxidant and anti-inflammatory properties; however, its molecular targets in diabetic retinal damage remain unclear.MethodsThis study investigated the protective effects of ZGN against high glucose (HG)-induced cytotoxicity in human ARPE-19 cells, focusing on the ROS/PARP-1/TRPM2 signaling pathway. The cells were exposed to HG (30 mM) and treated with ZGN (0-80 mu M) for 24 h.ResultsHG incubation significantly increased MDA, PARP-1, ROS, intracellular calcium ion ([Ca-2(+)]i), and pro-inflammatory cytokines (IL-1 beta and TNF-alpha) in ARPE-19 cells, while decreasing GSH levels and cell viability. ZGN significantly restored OS, reduced cytokine release, [Ca-2(+)]i, and preserved mitochondrial membrane potential. Western blot and fluorescence analyses showed that ZGN reduced TRPM2 protein expression and suppressed [Ca-2(+)]i overload. Moreover, pharmacological inhibition of TRPM2 with 2-APB and of PARP-1 with DPQ enhanced the cytoprotective effects of ZGN, confirming that the ROS/PARP-1/TRPM2 axis mediates HG-induced oxidative damage.ConclusionsThese findings suggest that ZGN protects ARPE-19 cells by integrating OS with [Ca-2(+)]i homeostasis, providing a mechanistic rationale for its potential therapeutic use in preventing OS-related retinal damage in DRP.Graphical AbstractHigh glucose (HG) exposure triggers excessive production of reactive oxygen species (ROS) in retinal pigment epithelial (ARPE-19) cells, leading to oxidative stress (OS), inflammation, mitochondrial depolarisation, and subsequent cell death. The overproduction of ROS activates poly (ADP-ribose) polymerase-1 (PARP-1), generating ADP-ribose (ADPR) and thereby stimulating the TRPM2 channel to promote Ca-2(+) influx. Elevated intracellular Ca-2(+) further disrupts mitochondrial homeostasis, amplifies ROS accumulation, and initiates apoptotic signaling cascades. Consequently, OS depletes cellular antioxidant defences (GSH) while increasing lipid peroxidation (MDA) and pro-inflammatory cytokines (IL-1 beta and TNF-alpha). ZGN interrupts this vicious cycle through its potent antioxidant and anti-inflammatory actions, enhancing GSH levels, scavenging ROS, suppressing MDA, IL-1 beta, and TNF-alpha production, and preventing TRPM2-mediated Ca-2(+) overload. By restoring OS, reducing inflammatory mediators, and preserving mitochondrial integrity, ZGN effectively prevents HG-induced apoptosis and cell death, underscoring its therapeutic potential against OS-associated retinal injury.
Protective Role of Zingerone Against High Glucose-Induced Retinal Pigment Epithelial Cell Damage Through Modulation of the TRPM2 Channel Pathway (Vol 53, 309, 2026)
(Springer, 2026) Cig, Esmanur; Yardimci, Mahmut; Cinar, Ramazan; Yildizhan, Kenan