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Öğe Alterations in Enzyme Activity of Carbonic Anhydrase, 6-phosphogluconate Dehydrogenase and Thioredoxin Reductase in Rats Exposed to Doxorubicin and Morin(Marmara Univ, Inst Health Sciences, 2020) Aggul, Ahmet Gokhan; Kuzu, Muslum; Kandemir, Fatih Mehmet; Kucukler, Sefa; Caglayan, CuneytObjectives: Carbonic anhydrase (CA), 6-phosphogluconate dehydrogenase (6PGD) and thioredoxin reductase (TrxR) enzymes are the essential biological molecules needed for metabolic processes in all living cells. This study was designed to investigate the activities of CA, 6PGD and TrxR enzymes in the brain, kidney, liver, heart and testis tissues of the rats exposed to doxorubicin (DOX) and morin. Methods: Male Wistar albino rats were randomly divided into three groups as control, morin and DOX, each of them containing 7 rats. At the end of the experimental procedure, CA, 6PGD, and TrxR enzyme activities in tissues of rats were determined spectrophotometrically. Results: In our study, we observed that DOX activated CA enzyme in liver and kidney tissues while inhibiting CA enzyme in the other tissues, activated 6PGD enzyme in the kidney, liver and heart tissues, and inhibited the TrxR enzyme in all the tissues. In addition, morin activated CA enzyme in the liver tissue while inhibiting CA enzyme in the brain, heart and testis tissues. Morin activated 6PGD enzyme activity while it inhibited TrxR enzyme in all the tissues. Conclusion: The findings showed that doxorubicin and morin had similar properties in the tissues as to their effect on enzyme activities.Öğe Assessment of Anticholinergic and Antidiabetic Properties of Some Natural and Synthetic Molecules: An In Vitro and In Silico Approach(Bentham Science Publ Ltd, 2024) Comakli, Veysel; Aygul, Imdat; Saglamtas, Ruya; Kuzu, Muslum; Demirdag, Ramazan; Akincioglu, Hulya; Adem, SevkiIntroduction: This study aimed to determine the in vitro and in silico effects of some natural and synthetic molecules on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and alpha-glucosidase enzymes. Background: Alzheimer's disease (AD) and Type II diabetes mellitus (T2DM) are considered the most important diseases of today's world. However, the side effects of therapeutic agents used in both diseases limit their use. Therefore, developing drugs with high therapeutic efficacy and better pharmacological profile is important. Objectives: This study sets out to determine the related enzyme inhibitors used in treating AD and T2DM, considered amongst the most important diseases of today's world. Methods: In the current study, the in vitro and in silico effects of dienestrol, hesperetin, L-thyroxine, 3,3',5-Triiodo-L-thyronine (T3) and dobutamine molecules on AChE, BChE and alpha-glycosidase enzyme activities were investigated. Results: All the molecules showed an inhibitory effect on the enzymes. The IC50 and Ki values of the L-Thyroxine molecule, which showed the strongest inhibition effect for the AChE enzyme, were determined as 1.71 mu M and 0.83 +/- 0.195 mu M, respectively. In addition, dienestrol, T3, and dobutamine molecules showed a more substantial inhibition effect than tacrine. The dobutamine molecule showed the most substantial inhibition effect for the BChE enzyme, and IC50 and Ki values were determined as 1.83 mu M and 0.845 +/- 0.143 mu M, respectively. The IC50 and Ki values for the hesperetin molecule, which showed the strongest inhibition for the alpha-glycosidase enzyme, were determined as 13.57 mu M and 12.33 +/- 2.57 mu M, respectively. Conclusion: According to the results obtained, the molecules used in the study may be considered potential inhibitor candidates for AChE, BChE and alpha-glycosidase.Öğe Attenuation of sodium arsenite-induced cardiotoxicity and neurotoxicity with the antioxidant, anti-inflammatory, and antiapoptotic effects of hesperidin(Springer Heidelberg, 2021) Kuzu, Muslum; Kandemir, Fatih Mehmet; Yildirim, Serkan; Caglayan, Cuneyt; Kucukler, SefaIn the scope of the study, the protective effect of hesperidin (HES), a flavanone glycoside, was investigated against sodium arsenite (NaAsO2, SA) induced heart and brain toxicity. For this purpose, 35 Sprague-Dawley male rats were divided into 5 different groups, 7 in each group. Physiological saline was given to the first group. Dose of 200 mg/kg of HES to the second group, 10 mg/kg dose of SA to the 3rd group, 100 mg/kg HES and 10 mg/kg SA to the 4th group, 200 mg/kg HES, and 10 mg/kg SA to the 5th group were given orally for 15 days. At the end of the study, biochemical, histopathological, and immunohistochemical examinations were performed on the heart and brain tissues of the rats. According to the results, SA increased malondialdehyde (MDA) and 8-hydroxy-2 '-deoxyguanosine (8-OHdG) levels and decreased glutathione (reduced, GSH) level and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in both tissues. Also, it increased cardiac lactate dehydrogenase (LDH) and creatine kinase isoenzyme-MB (CK-MB) activities and cardiac troponin-I level (cTn-I), cerebral acetylcholine esterase activity, nuclear factor kappa-B (NF-kappa B), tumor necrosis factor-alpha (TNF-alpha), interleukin-one beta (IL-1 beta), and cysteine aspartate-specific protease-3 (caspase-3) levels. In addition, as a result of histopathological examination, it was determined that SA damaged tissue architecture, and as a result of immunohistochemical examination, it increased cardiac Bcl-2-associated X protein (Bax) and cerebral glial fibrillary acidic protein (GFAP) expression. The results have also shown that HES co-treatment has an antioxidant, anti-inflammatory, antiapoptotic effect on SA-induced toxicity and aids to protect tissue architecture by showing a regulatory effect on all values. Consequently, it was determined that HES co-treatment had a protective effect on SA-induced heart and brain toxicity in rats.Öğe Cytotoxic effects, microbiological analysis and inhibitory properties on carbonic anhydrase isozyme activities of 2-hydroxy-5-methoxyacetophenone thiosemicarbazone and its Cu(II), Co(II), Zn(II) and Mn(II) complexes(Springer, 2021) Ucar, Asuman; Findik, Mukerrem; Kuzu, Muslum; Pehlivanoglu, Suray; Sayin, Ulku; Sayin, Zafer; Akgemci, Emine GulerMetal complexes of thiosemicarbazones have been receiving considerable attention in biological applications such as antimicrobial and anticancer therapies. In this work, Co(II), Zn(II) and Mn(II) complexes of 2-hydroxy-5-methoxyacetophenone thiosemicarbazone (HMAT) were synthesized for the first time and characterized by EPR, FT-IR, NMR, UV-Vis spectroscopies, TG/DSC and elemental analysis. X-ray powder diffraction analysis was carried out for Zn(II) complex. HMAT and its Cu(II), Co(II), Zn(II) and Mn(II) complexes were tested as enzyme inhibitory agents. All compounds are effective inhibitor of cytosolic carbonic anhydrase I and II isoforms (hCA I and II) enzymes. IC(50)values of HMAT and its Cu(II), Co(II), Zn(II) and Mn(II) complexes were determined as 93.35, 324.46, 25.67, 1.06 and 22.36 mu M for CA I isozyme and 99.02, 86.64, 57.76, 10.34 and 36.48 mu M for CA II isozyme, respectively. The evaluation of potential cytotoxic effects of the compounds was performed against normal epithelial breast mammary gland CRL-4010, estrogen-positive low metastatic MCF-7 and triple negative highly metastatic MDA-MB-231 breast adenocarcinoma cell lines by MTT assay. The results showed that the tested metal complexes have high cytotoxic effects than their ligand molecule. In particular, the Cu(II) complex displayed preciously high cytotoxic properties different from the others. Given these facts, the Cu(II) complex could be debated as potential chemotherapeutic molecule against drug-resistant breast cancer cells. Minimum inhibitory concentrations of the compounds against the test organisms were also detected for the microbiological analysis.Öğe Enzyme Inhibition and Antioxidant Activities of Asparagus officinalis L. and Analysis of Its Phytochemical Content by LC/MS/MS(Wiley-V C H Verlag Gmbh, 2023) Comakli, Veysel; Saglamtas, Rueya; Kuzu, Muslum; Karagoz, Yalcin; Aydin, Tuba; Demirdag, RamazanIn the study, water, ethanol, methanol, dichloromethane, and acetone extracts of Asparagus officinalis L. were obtained by maceration. DPPH*, ABTS(*+), FRAP, and CUPRAC methods determined the antioxidant capacities of all extracts. Moreover, the in vitro effects of extracts on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase (CA)-I, CA-II and a-Glycosidase were investigated. At a 10 mu g/ml concentration, the extract with the highest Fe3+ reduction capacity was ethanol (AE), and the extract with the highest Cu2+ reduction capacity was acetone (AA). AE for AChE (IC50= 21.19 mu g/ml) and a-Glycosidase (IC50: 70.00 mu g/ml), methanol (AM) for BChE (IC50= 17.33 mu g/ml), CA I and II (IC50= 79.65 and 36.09 mu g/ml, respectively) showed the most potent inhibition effect. The content analysis of acetone extract was performed with LC/MS-MS, the first three phytochemicals found most were p-Coumaric acid, rutin, and 4-hydroxybenzoic acid (284.29 +/- 3.97, 135.39 +/- 8.19, and 102.06 +/- 5.51 mu g analyte/g extract, respectively).Öğe In vitro Biological Activities of Different Extracts from Alcea dissecta(Marmara Univ, Inst Health Sciences, 2022) Taskin, Turgut; Kahvecioglu, Dilay; Turkoglu, Emir Alper; Dogan, Ahmet; Kuzu, MuslumObjective: Alcea genus belongs to Malvaceae family and this genus is represented by 85 taxa in the world and 21 taxa in the Flora of Turkey. The flowers of Alcea genus contain plenty of mucilage and are used for the treatment of respiratory diseases such as asthma and cough. Alcea dissecta is known as 'Govik, Hiro, Hero' in Turkey, and the flowers and leaves of this species have been used in the treatment of asthma, injury, colds, and gastrointestinal diseases in Turkey. To the best of our knowledge, there is no report on the effect of extraction methods on the biological activity of this plant. In addition, although this species is being used as a medical plant, there is no study of the antioxidant, antiurease, esterase, and anticholinesterase activity of the plant. Therefore, the aim of this study was to evaluate in vitro antioxidant, anti-urease, esterase, anticholinesterase activities of Alcea dissecta using a variety of extracts. Methods: The antioxidant activities of different extracts were examined by DPPH, ABTS, FRAP, and CUPRAC methods. The total phenolic compounds contained in the extracts were determined using the Folin-Ciocalteu reagent (FCR) method. Anti-urease and anticholinesterase activities of different extracts were evaluated by indophenol and Ellman methods respectively. In addition, esterase activities of plant extracts were determined. Results: In the present study, ethanol:water (1:1, v/v) and chloroform extracts obtained maceration method showed stronger DPPH and ABTS radical scavenging activity than other extracts. The chloroform extract obtained Soxhlet method was found to have higher FRAP and CUPRAC values than other extracts. It was also found that the ethanol extract obtained maceration method showed the most potent anti-urease and anticholinesterase activity. According to the results, the strongest inhibitory effect on both hCA I and II isoenzymes was shown by the petroleum ether extract obtained Soxhlet method. Conclusion: As a result, it was determined that different plant extracts have antioxidant, anti-urease, esterase, anticholinesterase activities. In addition, the data obtained from this study will shed light on future research on the biological activities of this species.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 Microvawe assisted synthesis of N-(methyl and methoxy) benzylidene-4-fluoroaniline derivatives and their carbonic anhydrase I and II inhibition properties(Acg Publications, 2019) Celik, Hulya; Kuzu, MuslumIn this study, some Schiff base derivatives (6a-f) were synthesized using a microwave method. The synthesized compounds were characterized by 1D, 2D NMR and mass spectral data. Their inhibitory effects were studied on carbonic anhydrase isozymes (hCA I and II), purified from human erythrocyte cells by Sepharose-4B-L-tyrosine-sulfanilamide affinity chromatography and the compounds N-3-Methylbenzylidene-4-fluoroaniline (6b), N-4-Methylbenzylidene-4-fluoroaniline (6c), N-2-Methoxybenzylidene-4-fluoroaniline (6d) showed moderate activity on hCAII in the range of IC50 values.Öğe Oleuropein and Verbascoside - Their Inhibition Effects on Carbonic Anhydrase and Molecular Docking Studies(Japan Oil Chemists Soc, 2021) Aggul, Ahmet Gokhan; Taslimi, Parham; Kuzu, Muslum; Uzun, Naim; Bilginer, Sinan; Gulcin, IlhamiRecently, carbonic anhydrase (CA, E.C.4.2.1.1) inhibitors from natural product have paved the way for novel drug design in the treatment and prevention of some global diseases such as glaucoma, diabetes, and cancer. For this purpose, the inhibition effects of oleuropein and verbascoside from olive (Olea europaea L.) oil on human carbonic anhydrase I, and II (hCA I, and II) isoenzymes were evaluated in the current study. The inhibition effects of both natural compounds were determined by the esterase activity (in vitro). IC50 value of oleuropein and verbascoside was calculated as 1.57 and 1.73 mu M for hCA I isoenzyme, respectively. At the same manner, K-i values were determined as 1.25 +/- 0.42 and 2.00 +/- 0.42 mu M, respectively. Then, IC50 value of each compound for hCA II isoenzyme was calculated as 2.23 and 1.90 mu M, respectively. Similarly, K-i values were determined as 2.37 +/- 0.87 mu M and 1.49 +/- 0.33 mu M, respectively. Also, the inhibitory effects and potent binding mechanisms of oleuropein and verbascoside on hCA I, and II isoenzymes were realized by molecular docking studies. Consequently, both natural phenolic compounds demonstrated the potent inhibition profiles against the both isoenzymes. Therefore, we believe that these results may break new ground in the drug development for the treatment of some global disorders.Öğe The protective effect of esculetin against aluminium chloride-induced reproductive toxicity in rats(Wiley, 2021) Turk, Erdinc; Ozan Tekeli, Ibrahim; Ozkan, Huseyin; Uyar, Ahmet; Cellat, Mustafa; Kuzu, Muslum; Yavas, IlkerOne of the prominent health problems caused by Aluminium was the decrease in male fertility rates. In the study, the protective effect of Esculetin (ESC) against the reproductive toxicity induced by Aluminium chloride (AlCl3) was investigated. For this purpose, AlCl3 was administrated to Wistar Albino rats at a dose of 34 mg/kg and ESC was administrated at a dose of 50 mg/kg for 70 days. It was determined that AlCl3 treatment reduced sperm motility and concentration, increased dead/live rate and abnormal sperm rate. It decreased serum testosterone level, and co-treatment of ESC significantly regulated these values. In the AlCl3-treated group, MDA level increased and GSH level, GPx and CAT activities decreased compared with those of the control group. However, co-treatment of ESC showed an amelioratory effect on the values except for CAT activity. It was observed that the expression level of NRF-2 increased in the ESC and AlCl3 + ESC groups, and NF-kappa B increased in the AlCl3 group with the control group. It was determined that Caspase-3 expression decreased, and Bcl-2 expression increased in AlCl3 + ESC group compared to AlCl3 group. It was also determined that AlCl3-induced tissue injury was significantly prevented by ESC co-treatment.Öğe Protective effect of Smilax excelsa L. pretreatment via antioxidant, anti-inflammatory effects, and activation of Nrf-2/HO-1 pathway in testicular torsion model(Wiley, 2022) Cellat, Mustafa; Isler, Cafer Tayer; Uyar, Ahmet; Kuzu, Muslum; Aydin, Tuba; Etyemez, Muhammed; Turk, ErdincThe protective effects of the ethanol extract of Smilax excelsa L. (SE) leaves were investigated on testicular tissue of rats with a torsion model in this study. The chemical composition of the extract was detected by means of liquid chromatography with tandem mass spectrometry (LC-MS/MS). SE extract was given for 21 days before torsion was created in the treatment group. The sperm parameters of the torsion group were impaired, and there was an increase in MDA level as well as a decrease in GSH level and GPx activity compared to the control group. TNF-alpha and NF-kappa B levels in the torsion group increased as compared to those in the control group. The expression levels of Nrf-2 and HO-1 were lower in the torsion group than those in the control group. The SE pretreatment group has improved sperm, oxidative stress, and inflammatory markers when compared to the torsion group, and the Nrf-2/HO-1 pathway was activated. Practical applications Smilax excelsa L. is a plant with economic value used in traditional medicine in the treatment of stomachache, bloating, and breast cancer in Northwest Anatolia. It has an antioxidant effect due to the flavonoids and anthocyanins it contains. The protective effect against ischemia-reperfusion-induced tissue and reproductive damage in testicular tissue were demonstrated with the study. When the histological examinations of the tissues were evaluated, it was found that morphological structure of the tissues was retained in the treatment group. The findings indicate that SE prevents tissue damage in the torsion model by antioxidant and anti-inflammatory effects and activating Nrf-2/HO-1 pathway.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 Some phenolic natural compounds as carbonic anhydrase inhibitors: An in vitro and in silico study(Wiley-V C H Verlag Gmbh, 2022) Aggul, Ahmet Gokhan; Uzun, Naim; Kuzu, Muslum; Taslimi, Parham; Gulcin, IlhamiThis paper presents experimental and molecular docking studies on the inhibitory effects of tyrosol, hydroxytyrosol, luteolin, diosmetin, caffeic acid, luteolin 7-O-glycoside, and apigenin 7-O-glycoside from olive (Olea europaea L.) leaf against human carbonic anhydrase (hCA, E.C.4.2.1.1) isozymes I and II. After these isozymes were separately purified, their activities were determined using the esterase activity. IC50 values for hCA I and II were calculated as 2.02-11.38 mu M and 2.23-9.05 mu M, respectively. The compounds were identified as CA inhibitors, with K-i values in the ranges of 1.66-9.17 mu M for the hCA I isozyme and 1.49-14.21 mu M for hCA II. The inhibitory effects of these natural compounds were also compared to acetazolamide, which is a potent inhibitor of both CA isozymes. Our results may contribute to the synthesis of new CA inhibitors and pave the way for new drug design in the treatment of a number of diseases including cancer, obesity, diabetes, and glaucoma.Öğe Tyrosol improves ovalbumin (OVA)-induced asthma in rat model through prevention of airway inflammation(Springer, 2021) Cellat, Mustafa; Kuzu, Muslum; Isler, Cafer Tayer; Etyemez, Muhammed; Dikmen, Nursel; Uyar, Ahmet; Gokcek, IshakAsthma is an inflammatory disease that affects many people around the world, especially persons at paediatric age group. The effectiveness of tyrosol, a natural phenolic compound, was examined in the asthma model induced by ovalbumin (OVA). For this purpose, four groups, each consisting of eight rats, were arranged. For 21 days, physiological saline solution was treated to the control group and OVA was treated to the groups of OVA, OVA + dexamethasone (Dexa) and OVA + tyrosol groups, intraperitoneally and through inhalation. Additionally, 0.25 mg/kg Dexa was treated to the OVA + Dexa group and 20 mg/kg tyrosol to the OVA + tyrosol group by oral gavage. Serum, blood, bronchoalveolar lavage fluid (BALF) and lung tissues of the rats were examined. It was observed that MDA level decreased, GSH level and GPx activity increased, and there was no change in CAT activity in lung tissues of the tyrosol treatment groups. It was also observed that NF-kappa B, TNF-alpha, IL-4, IL-5, IL-13, IFN-gamma and IgE levels decreased compared to the OVA group in lung tissue and serum samples except for serum NF-kappa B and IL-4. However, no effect on IL-1 beta level was observed. In addition, it was determined that tyrosol treatment increased the IL-10 level on both tissue samples. The results of the histopathological investigation of lung tissue showed that tyrosol significantly ameliorated OVA-induced histopathological lesions. Additionally, PAS staining showed that mucus hypersecretion was significantly reduced with the use of tyrosol. In addition, it was determined that the number of eosinophils decreased significantly in blood and BALF samples. The obtained results showed that tyrosol possessed antioxidant and anti-inflammatory features on OVA-induced rats and preserved tissue architecture.Öğe Tyrosol improves ovalbumin (OVA)-induced asthma in rat model through prevention of airway inflammation (Jul, 10.1007/s00210-021-02117-y, 2021)(Springer, 2021) Cellat, Mustafa; Kuzu, Muslum; Isler, Cafer Tayer; Etyemez, Muhammed; Dikmen, Nursel; Uyar, Ahmet; Gokcek, Ishak[No abstract available]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.
