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    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, Cuneyt
    Objectives: 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.
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    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, Ilhami
    Recently, 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.
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    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, Ilhami
    This 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.
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    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, Akin
    The 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.