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Öğe Ameliorating effect of kisspeptin-10 on methotrexate-induced sperm damages and testicular oxidative stress in rats(Wiley, 2018) Guvenc, Mehmet; Aksakal, MesutThe purpose of this study was to determine the kisspeptin-10 (Kiss) administration on the damages in testicular oxidant-antioxidant system, reproductive organ weights and some spermatological characteristics resulted from methotrexate (MTX) exposure. Group 1 (n:6) received saline only; group 2 (n:6) received 50 nmol/kg kisspeptin-10 for 10 days; group 3 (n:10) received single-dose methotrexate 20 mg/kg; and group 4 (n:10) received MTX 20 mg/kg single dose and, after 3 days, received kisspeptin-10, 50 nmol/kg, lasted for 10 days by intraperitoneal injection. At the end of the study, malondialdehyde levels were found to have increased following the application of MTX while showing a significant reduction in group 4 with Kiss administration. With respect to the spermatological parameters, administering MTX decreased motility and increased the rates of abnormal spermatozoa in group 2, while improvements were observed in group 4 in the form of increased motility in the spermatozoa and fewer abnormal spermatozoa. In addition, Kiss treatment provided statistically significant increases in the absolute weight of the seminal vesicles and the relative weights of the right cauda epididymis and seminal vesicles resulting from MIX administration. MTX administration damaged some spermatological parameters and increased oxidative stress when compared to the control group. However, Kiss treatment was observed to mitigate these adverse effects as demonstrated by the improvements in coadministration of Kiss and MTX when compared to the MTX group. It is concluded that Kiss treatment may reduce MTX-induced reproductive toxicity as a potential antioxidant compound.Öğe Ameliorative Effects of Oleuropein on Lipopolysaccharide-Induced Acute Lung Injury Model in Rats(Springer/Plenum Publishers, 2021) Dikmen, Nursel; Cellat, Mustafa; Etyemez, Muhammed; Isler, Cafer Tayer; Uyar, Ahmet; Aydin, Tuba; Guvenc, MehmetAcute lung injury (ALI) is one of the most common causes of death in diseases with septic shock. Oleuropein, one of the important components of olive leaf, has antioxidant and anti-inflammatory effects. The objective of this study was to investigate the effects of oleuropein on lipopolysaccharide (LPS)-induced ALI in rats. Oleuropein was administered to rats at a dose of 200 mg/kg for 20 days and LPS was given through intratracheal administration to induce ALI. The study was terminated after 12 h. The results showed that in the group treated with oleuropein, inflammatory cytokines and oxidative stress decreased in serum, bronchoalveolar lavage fluid (BALF), and lung tissue, and there were significant improvements in the picture of acute interstitial pneumonia (AIP) caused by LPS in histopathological examination. Based on the findings of the present study, oleuropein showed protective effects against LPS-induced ALI.Öğe Effects of carvacrol on experimental nephrolithiasis in female rats(Taylor & Francis Ltd, 2023) Kutlu, Tuncer; Guvenc, MehmetWe induced experimental nephrolithiasis in female rats using ethylene glycol (EG) and ammonium chloride (AC). We investigated the effects of carvacrol, an essential oil with antioxidant and anti-inflammatory properties, on nephrolithiasis using histopathology, immunohistochemistry and biochemistry. We used 40 female rats divided into four equal groups: control group, administered olive oil; carvacrol group, administered carvacrol in olive oil; nephrolithiasis group, administered EG and AC to induce experimental nephrolithiasis; treatment group with induced nephrolithiasis and administered carvacrol in olive oil. We observed no significant difference in crystal accumulation in the treatment group compared to the nephrolithiasis group. We found a significant reduction in hydropic degeneration of tubules and degree of inflammatory cell infiltration of intertubule areas. We also found a significant reduction in immunohistochemical staining of macrophage- and monocyte-specific antigens. Carvacrol treatment reversed the induced nephrolithiasis, increased malondialdehyde and urea, and decreased levels of glutathione peroxidase and catalase. Although carvacrol did not decrease crystal accumulation, it reduced pathological and biochemical damage, and improved kidney function by lowering the serum urea level.Öğe Effects of Dexamethasone on Bupivacaine-Induced Peripheral Nerve Injection Injury in the Rat Sciatic Model(Taylor & Francis Inc, 2021) Comez, Mehmet Selim; Borazan, Yakup; Ozgur, Tumay; Isler, Cafer Tayer; Cellat, Mustafa; Guvenc, Mehmet; Altug, Muhammed EnesIntroduction The aim of this study was to investigate the effect of perineural dexamethasone against intraneural bupivacaine. Material and Methods Rats were divided into 9 groups with 6 animals in each group; Group 1 (Intraneural saline 600 mu L-2ndday), Group 2 (Intraneural saline 600 mu L-7th day), Group 3 (Intraneural saline 600 mu L + perineural dexamethasone 0.5 mg/kg-2nd day), Group 4 (Intraneural saline 600 mu L + perineural dexamethasone 0.5 mg/kg-7th day), Group 5 (Intraneural bupivacaine 10 mg/kg-2nd day), Group 6 (Intranueral bupivacaine 10 mg/kg-7th day), Group 7 (Intraneural bupivacaine 10 mg/kg + perineurald exam ethasone 0.5 mg/kg-2nd day), Group 8 (Intraneural bupivacaine 10 mg/kg + perineural dexamethasone 0.5 mg/kg-7th day), Group 9 (Control group). At the end of the application period, histopathological and immunohistochemical examinations were analyzed. Results and Conclusion It was observed that caspase 3 levels significantly increased in the 5th and 6th groups compared to the 1st and 2nd groups (p < 0.01). However, in the 7th and 8th groups, these levels were similar with 1st and 2nd groups. While a significant decrease in S 100 levels was detected in group 6 (p < 0.05), a significant increase occurred in Group 8 and reached the same levels as Group 2. According to histopathological evaluation, edema, vacuolization and myelin degeneration were significantly increased in groups 5 and 6 (p < 0.05). However, in the 8th group, the mentioned data showed a significant decrease and reached the same levels as group 2. As a result, perineural dexamethasone was found to have protective effects against intraneural bupivacaine induced sciatic nerve damage.Öğe Effects of thymol and carvacrol on sperm quality and oxidant/antioxidant balance in rats(Taylor & Francis Ltd, 2019) Guvenc, Mehmet; Cellat, Mustafa; Gokcek, Ishak; Yavas, Ilker; Ozsoy, Yule YurdagulIn this study, we have investigated the effects of different doses of thymol (T) and carvacrol (C) on sperm quality oxidative stress and antioxidant system. For this purpose, 49 rats were divided into seven groups (7 rats in each group): 1st Group (control); 2nd Group T-10 (thymol 10?mg/kg), 3rd Group T-20 (thymol 20?mg/kg), 4th Group C-10 (carvacrol 10?mg/kg), 5th Group C-20 (carvacrol 20?mg/kg), 6th Group T?+?C-10 (thymol 10?mg/kg?+?carvacrol 10?mg/kg) and 7th Group T?+?C-20 (thymol 20?mg/kg?+?carvacrol 20?mg/kg). The duration of the experiment was 10?weeks for all animals. During the study, sperm quality parameters (motility, concentration, abnormal spermatozoa and live?dead sperm ratio), biochemical parameters [malondialdehyde (MDA), reduced glutathione(GSH), glutathione peroxidase (GSH-Px), catalase (CAT), AST, ALT, GGT, urea and creatinine] were analysed, and histopathological examination was performed. The study results showed that monotherapies of thymol and carvacrol significantly decreased MDA levels in testicles, liver and kidney tissues compared to the control group (p?Öğe Hepatoprotective Activity of Linalool in Rats Against Liver Injury Induced by Carbon Tetrachloride(Verlag Hans Huber, 2020) Altinok-Yipel, Fulya; Tekeli, Ibrahim Ozan; Ozsoy, Sule Yurdagul; Guvenc, Mehmet; Kaya, Alpaslan; Yipel, MustafaThis study aimed to investigate and compare hepatoprotective activity of Coriandrum sativum (Cs) and it is major component linalool (Ln) against experimentally induced hepatotoxicity in rats. Essential oil of Cs was isolated by hydrodistillation method and chemical composition was determined by GS-MS analysis. 42 male Wistar Albino rats were divited into 7 groups each containing 6. The experimental groups were designed as: Normal control group, 1 ml/kg CCl4 administirated group, 25 mg/kg Silymarin and CCl4 administirated group, 100 and 200 mg/kg Cs and CCl4 administirated groups, 100 and 200 mg/kg Ln and CCl4 administered groups. The protective activities were determined according to the results of liver biomarkers (AST, ALT, ALP), antioxidant parameters (GSH, GPx, CAT), lipid peroxidation (MDA) and histopathological examination. Linalool percentage of Cs was 81.6%. The groups treated with linalool (100 and 200 mg/kg) (p < 0.01) and coriander (200 mg/kg) (p < 0.05) had significantly reduced AST (262-375) and ALT (101-290) levels (U/L) compared to the CCl4 (600-622) group. The levels (nmol/g protein) of MDA (11-12) were significantly lower (p < 0.01), the levels of GSH (11-12) and the activities of CAT (23-24) were significantly higher (p < 0.01) in linalool groups (100 and 200 mg/kg) compared to the CCl4 (18-5-10 respectively) group. These results were also supported by histopathological findings and indicate that Cs and Ln shows hepatoprotective activity against liver damage. In this regard, evaluation of activities of major components are needed to compare to medicinal plants in experimental diseases models.Öğe Investigation of the effects of safranal on the experimentally created rheumatoid arthritis model in rats(Wiley, 2022) Cellat, Mustafa; Isler, Cafer T.; Kutlu, Tuncer; Kuzu, Muslum; Etyemez, Muhammed; Alakus, Halil; Guvenc, MehmetRheumatoid arthritis (RA) is a systemic chronic disease characterized by inflammation and synovitis. More effective treatment methods with less side effects need to be developed. In this context, current study investigated the therapeutic effects of safranal in a model of complete Freund's adjuvant (CFA)-induced RA. The control group was given 1 ml of saline orally starting from the 8th day, and 0.2 ml of CFA was given to the RA, RA + Safranal and RA + Methotrexate (MTX) groups on the 0th day of the experiment. Starting from the 8th day of the experiment, 1 ml of saline was given to the RA group, safranal was given at 200 mg/kg of body weight to the RA + MTX group, and 3 mg/kg of MTX to the RA + MTX group twice a week. The results showed that weight gain decreased in the RA group compared to the control group while arthritis index score, thymus index, and planter temperature were found to be increased. Additionally, a deterioration in blood parameters, an increase in alanine aminotransferase, aspartate aminotransferase, urea, creatinine, C-reactive protein, and malondialdehyde levels, and a decrease in reduced glutathione levels and glutathione peroxidase and catalase (CAT) activities were seen while tumor necrosis factor-alpha, interleukin-6 (IL-6), cyclooxygenase-2, nuclear factor kappa B levels were found to be increased. However, the safranal had a regulatory effect on all the values, except IL-6 and CAT, and blood parameters. Moreover, histopathological examination revealed that safranal reduced inflammatory cell infiltration and edema.Öğe Nobiletin attenuates acetaminophen-induced hepatorenal toxicity in rats(Wiley, 2020) Guvenc, Mehmet; Cellat, Mustafa; Gokcek, Ishak; Ozkan, Huseyin; Arkali, Gozde; Yakan, Akin; Ozsoy, Sule YurdagulThe study aimed to examine the effects of nobiletin on the toxicity model induced with acetaminophen (APAP). For this purpose, 24 adult male rats were equally divided into four groups. The groups were the control group (group 1); dimethyl sulfoxide only, the APAP group (group 2) received a single dose of APAP 1000 mg/kg on the 10th day of experiment; the Nobiletin group (group 3), nobiletin (10 mg/kg) for 10 days; and the APAP + Nobiletin group (group 4), nobiletin (10 mg/kg) for 10 days with a single dose of APAP (1000 mg/kg) administered on the 10th day and the experiment ended after 48 hours. At the end of the study, a significant increase in malondialdehyde, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels and a significant decrease in glutathione levels, glutathione peroxidase activities and nuclear factor erythroid-derived 2-like 2 (Nrf-2) and heme oxygenase-1 (HO-1) expressions were observed with APAP application in liver and kidney tissues. Serum aspartate transaminase (AST), alanine transaminase (ALT), urea, and creatinine levels were also significantly increased in the APAP group. However, nobiletin treatment in group 4 reversed oxidative stress and inflammatory and histopathological signs caused by APAP. It is concluded that nobiletin may be a beneficial substance that confers hepatorenal protection to APAP-induced toxicity via antioxidant and anti-inflammatory mechanisms.Öğe Nobiletin Protects from Renal Ischemia-Reperfusion Injury in Rats by Suppressing Inflammatory Cytokines and Regulating iNOS-eNOS Expressions(Springer/Plenum Publishers, 2020) Guvenc, Mehmet; Cellat, Mustafa; Uyar, Ahmet; Ozkan, Hueseyin; Gokcek, Ishak; Isler, Cafer Tayer; Yakan, AkinIschemia-reperfusion injury is an organ failure caused by hypoxia and reperfusion, which is closely associated with oxidative stress and inflammation. In this study, we investigated whether nobiletin had protective effects on inflammatory parameters, oxidative damage, iNOS-eNOS expressions, and histopathological structure of renal tissue in rats with renal ischemia-reperfusion injury. For this purpose, 24 rats were divided into 4 groups: group 1 (Control), group 2 (Ischemia-Reperfusion-IR), group 3 (Nobiletin-10 mg/kg p.o.), group 4 (Nobiletin + IR). The study was continued for 7 days. At the end of the study, urea (p < 0.05), creatine (p < 0.05), MDA (p < 0.001), TNF-alpha (p < 0.001), IL-1 beta (p < 0.05), and IL-6 (p < 0.001) levels increased in the IR group; however, a significant decrease occurred in group 4 (Nobiletin + IR) and it reached the control group levels. In the IR group, GSH (p < 0.01) levels, and GSH.Px (p < 0.01) and CAT (p < 0.05) activities decreased whereas they increased significantly in group 4 (Nobiletin + IR) and reached the same levels as the control group. In histopathological analyses, destruction and increased iNOS-eNOS expressions in the IR group showed a significant decrease in group 4 (Nobiletin + IR). As a result, the application of nobiletin has shown that it has protective effects by reducing kidney damage caused by IR injury.Öğe The protective effect of Boswellic acid and Ellagic acid loaded, colon targeted, and pH-sensitive N-succinyl chitosan in ulcerative colitis rat model(Elsevier, 2022) Yipel, Mustafa; Tekeli, Ibrahim Ozan; Altinok-Yipel, Fulya; Coskun, Pinar; Aslan, Abdullah; Guvenc, Mehmet; Beyazit, NeslihanTargeted drug delivery systems that provide therapeutic activity with lower concentrations of both herbal and other substances, while reducing access to non-target sites and undesirable effects; have an important potential for future projections in terms of pharmacological and toxicological studies. The present study aimed to investigate the protective effects of Acetyl 11-keto-beta-boswellic acid (AKBA) and Ellagic acid (EA) loaded, colon targeted, and pH-Sensitive N-succinyl chitosans (NsCh) in ulcerative colitis (UC) model induced by acetic acid (AA) in rats. The physicochemical characterization (elemental analysis, FT-IR, DSC, XRD, SEM, NMR) analyses, swelling, and releasing tests of NsCh's suggested that AKBA and EA were successfully loaded to pH-sensitive polymer and targeted to the colon. The targeted AKBA and EA were administered to Wistar rats (n:30, 5 groups) and damage, inflammatory cytokine, protein expression, oxidative stress, and antioxidant parameter levels in colon tissues of the groups were determined. Increase in the levels of CAT, GPx activities, and decrease in necrosis, inflammation, and levels of MDA, TNF-alpha, COX-2, NF-kB were observed in the targeted EA and AKBA groups compared to the UC group. The potential protective effect of EA and AKBA loaded, colon-targeted, pH sensitive controlled releasing system against UC and the potential to be licensed preparations by completing the next stages of in vitro and in vivo studies were demonstrated.Öğe Protective Effects of Tyrosol Against DSS-Induced Ulcerative Colitis in Rats(Springer/Plenum Publishers, 2019) Guvenc, Mehmet; Cellat, Mustafa; Ozkan, Huseyin; Tekeli, Ibrahim Ozan; Uyar, Ahmet; Gokcek, Ishak; Isler, Cafer TayerIn this study, the effects of tyrosol were investigated in DSS-induced experimental ulcerative colitis model. For this purpose, rats were divided into five groups of seven rats in each: control group, colitis group (DSS-4%), tyrosol group (tyrosol 20 mg/kg), sulfasalazine (sulfasalazine+DSS 100 mg/kg), and treatment group (tyrosol+DSS 20 mg/kg). In the study, the active substances were administered to all animals for a period of 21 days. At the end of the study, malondialdehyde (MDA) levels increased (p < 0.001); GSH level (p < 0.05) along with GSH.Px (p < 0.01) and CAT (p < 0.001) activities decreased in the DSS-induced colitis group. However, with the administration of tyrosol, MDA and GSH levels along with GSH.Px and CAT activities came to the same levels as the control group. In the colitis group, an increase occurred in IL-6, COX-2, and NF-kappa B parameters, which created a significant difference compared to the control group (p < 0.001). Similarly, TNF-alpha levels also significantly increased with the administration of DSS (p < 0.05) which created a significant difference compared to the control group, while there was no difference among the other groups. As for the Nrf-2 data, it decreased with the administration of DSS which created a significant difference compared to the control group (p < 0.05), while there was no difference in other groups. In the colitis-induced group, IL-6, COX-2, and NF-kappa B gene expression levels also similarly increased but returned to the normal levels with the administration of tyrosol. In the histopathological scoring, the negativity that increased with the administration of DSS returned to the normal levels with the administration of tyrosol+DSS. In conclusion, according to the data obtained, tyrosol fixed the destruction picture in the DSS-induced colitis model, giving rise to thought that it has a protective effect.Öğe Protective Effects of Tyrosol Against DSS-Induced Ulcerative Colitis in Rats (vol 42, pg 1680, 2019)(Springer/Plenum Publishers, 2019) Guvenc, Mehmet; Cellat, Mustafa; Ozkan, Huseyin; Tekeli, Ibrahim Ozan; Uyar, Ahmet; Gokcek, Ishak; Isler, Cafer Tayer[Abstract Not Available]Öğe Safranal's therapeutic effects in rat models of polycystic ovary syndrome(Springernature, 2024) Cellat, Mustafa; Kuzu, Muslum; Guvenc, Mehmet; Yuksel, Murat; Kanat, Ozgur; Bozkurt, Yesim Akaydin; Etyemez, MuhammedPolycystic ovary syndrome is one of the leading causes of female infertility in reproductive age. In this work, the protective effects of safranal against letrozole-induced polycystic ovary syndrome in rats were examined. For this purpose, 32 Wistar albino female rats were split into four groups. Each group received the following treatments for 21 days: Group 1 received carboxymethylcellulose (1%, 2 ml/kg); Group 2, letrozole (1 mg/kg), Group 3, safranal (200 mg/kg); and Group 4 letrozole and safranal via oral gavage. We identified estrus cycles in the rats and analyzed various parameters in their serum and ovarian tissues, as well as histopathologic findings. The parameters studied included C-reactive protein, glucose, total cholesterol, triacylglyceride, high-density lipoprotein, low-density lipoprotein, follicle-stimulating hormone, estradiol, and luteinizing hormone levels in serum. Additionally, the study measured malondialdehyde, glutathione, glutathione peroxidase, and catalase levels in ovarian tissue. We also examined tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta parameters in serum and ovarian tissues, as well as nuclear factor erythroid 2-related factor-2 and heme oxygenase-1 protein levels. In the letrozole group, the estrus cycle was disrupted, and all parameters, except for glutathione and glutathione peroxidase, showed impairments compared to the control group. The findings showed that glucose, triacylglyceride, catalase, and heme oxygenase-1 levels slightly improved after safranal treatment, however, other parameters showed statistically significant improvements. Furthermore, safranal treatment reduced the development of cystic follicles while preserving tissue architecture, as revealed by histopathologic findings. Based on the results obtained, it may be argued that safranal's antioxidant and anti-inflammatory properties, along with its ability to regulate sex hormone levels and manage dyslipidemia, make it a promising solution for patients with polycystic ovary syndrome.Öğe Tyrosol prevents AlCl3 induced male reproductive damage by suppressing apoptosis and activating the Nrf-2/HO-1 pathway(Wiley, 2020) Guvenc, Mehmet; Cellat, Mustafa; Gokcek, Ishak; Arkali, Gozde; Uyar, Ahmet; Tekeli, Ibrahim Ozan; Yavas, IlkerAluminium is a ubiquitous element that occurs naturally in the soil making human exposure to it is unavoidable. Tyrosol is present in olive oil and is known to have antioxidant effects. Therefore, the present study explores the toxic effects of aluminium chloride (AlCl3) and evaluates the possible protection by tyrosol in male rats. Testicular injury was induced by the administration of AlCl3 (34 mg kg(-1) day(-1)). Rats were treated with either tyrosol (20 mg kg(-1) day(-1)) or AlCl3 (34 mg kg(-1) day(-1)). The experiment lasted for 10 weeks. Biochemical, histopathological and protein expression profiles were determined to decipher the role of tyrosol in protecting the cellular damage. Further, histomorphometric analyses of testes showed deranged architecture along with other noted abnormalities. AlCl3 group rats' testes showed decreased GSH levels, CAT activities, Nrf-2, HO-1, bcl-2 expressions and sperm motility whereas increased caspase-3 expressions, MDA levels, abnormal and dead/live sperm ratio. However, tyrosol treatment attenuated these changes. The present results demonstrate the beneficial role of tyrosol treatment in AlCl3 induced testicular toxicity alterations of rat.Öğe Tyrosol retards induction of fibrosis in rats(Wiley, 2021) Kutlu, Tuncer; Ozkan, Huseyin; Guvenc, MehmetLiver fibrosis, which still does not have a standard treatment due to its complex pathogenesis, is an important cause of mortality and morbidity. In this study, it was aimed to examine the possible protective and antifibrotic effects of tyrosol on the liver through histopathologic, immunohistochemical, biochemical, and molecular methods in rats with chronic liver damage induced by thioacetamide (TAA). The study was carried out in four groups with eight rats in each group. Created groups are, respectively, control, TAA, tyrosol and TAA +tyrosol. Chronic liver damage was induced in the TAA and TAA +tyrosol groups by the addition of TAA (200 mg/L) to drinking water. Tyrosol (20 mg/kg/b.w./daily) was administered by oral gavage to tyrosol and TAA +tyrosol groups for 10 weeks. The results of this study demonstrate that the consumption of tyrosol alleviated the histopathologic changes such as inflammation, degeneration, and especially fibrosis induced by TAA in the liver. In addition, administration of tyrosol significantly attenuated alpha-smooth muscle actin (alpha-SMA) expression and apoptosis expression. Biochemically, it was determined that tyrosol increased glutathione (GSH) level, glutathione peroxidase (GSH.Px), and catalase (CAT) activities and showed antioxidant efficacy by reducing malondialdehyde (MDA) level. Moreover, it reduced inflammation and fibrosis by decreasing gene expression levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-beta 1). Western blot analysis also revealed similar results in TGF-beta 1 expression. As a result, tyrosol suppressed fibrogenesis thanks to its antioxidant, anti-inflammatory, and anti-apoptotic effects and showed an antifibrotic effect in the liver. Practical applications It is stated that tyrosol, a natural phenolic antioxidant found in olive oil, has neuroprotective, cardioprotective, anti-inflammatory, and anticancer properties. In this study, tyrosol suppressed fibrogenesis thanks to its antioxidant, anti-inflammatory, and anti-apoptotic effects and showed an antifibrotic effect in the liver. Olive oil has an important place in the Mediterranean diet, which reduces the incidence of chronic diseases. It is thought that the anti-fibrotic effect of tyrosol plays a role in this feature. As a result, it is thought that tyrosol can be used to prevent or slow down chronic liver diseases.Öğe Zingerone protects liver and kidney tissues by preventing oxidative stress, inflammation, and apoptosis in methotrexate-treated rats(Taylor & Francis Ltd, 2022) Turk, Erdinc; Guvenc, Mehmet; Cellat, Mustafa; Uyar, Ahmet; Kuzu, Muslum; Aggul, Ahmet Gokhan; Kirbas, AkinThe clinical use of drugs used in the treatment of diseases is limited due to the toxic side effects, and many studies have been conducted to benefit from herbal adjuvant therapies recently to eliminate these effects. In this study, the protective effect of zingerone against liver and kidney damage generated in rats through methotrexate (MTX). Histopathological investigations were performed to determine tissue damage caused by MTX and the healing effect of zingone and liver function markers such as serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and renal function markers such as urea, creatine, and aquaporin-1 (AQP-1) were measured. The effects of MTX and protective properties of zingerone on oxidative stress were investigated through the measurement of malondialdehyde and reduced glutathione (GSH) levels, catalase (CAT), and glutathione peroxidase (GPx) enzyme activities. The anti-inflammatory effect of zingerone was determined by measuring the cytokine levels causing inflammation such as nuclear factor-kappa B (NF-kappa B), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta), and its effects on apoptosis were determined by immunohistochemical analysis of caspase-3 and B-cell lymphoma-2 (Bcl-2) expression levels. According to the results obtained within the scope of the study, it was determined that zingerone treatment prevented the increase in MTX-induced liver and kidney function markers, showed healing effects on antioxidant parameters degraded in both tissues, and decreased the inflammation parameters. It was determined that it also prevented apoptosis and possessed a protective effect on disrupted tissue architecture by decreasing the increased caspase-3 expression and increasing the decreased Bcl-2 level.
