An Evaluation of Damages Caused by Doxorubicin in Liver Tissue and Potential Protective Effect of Propolis on These Damages

Objective: Doxorubicin (DOX), one of the chemotherapeutic drugs utilized in cancer treatment, has limited clinical use due to its serious toxic effects on non-target organs. The purpose of this study is to reveal the harmful effects of DOX in rat liver and the possible protective effect of propolis (PRPLS), a mixture of various herbal products collected by honeybees, on these damages by Attenuated Total Reflection-Fourier Transformation Infrared (ATR-FTIR) spectroscopy. Methods: Sprague dawley rats were separated into 4 groups; control, DOX (cumulative dose: 15 mg/kg), PRPLS (200 mg/kg) and DOX + PRPLS. The rats were given 200 mg/kg PRPLS by oral gavage daily for 20 consecutive days and 2.5 mg/kg DOX intraperitoneally on days 10, 12, 14, 16, 18 and 20 of the experiment. 24 hrs after the last administrations, liver samples were collected and examined by ATR-FTIR spectroscopy. Results: DOX caused a decrease in the amount of glycogen and nucleic acids, an increase in the amount of lipids and proteins and some important changes in the metabolism, structure and conformation of these molecules in the liver. DOX also induced lipid peroxidation, an increase in membrane fluidity, a decrease in membrane order and protein denaturation. PRPLS did not induce any toxic effect on the liver when it was given alone and PRPLS administered before DOX was not effective to eliminate these harmful effects of DOX. Conclusions: DOX caused significant structural and compositional changes in liver tissue and PRPLS was inadequate to prevent these changes at the dose and time used here.Duzce University-Research Fund, BAP [2019.05.01.936]This work was supported by the Duzce University-Research Fund, BAP (2019.05.01.936)

Investigation of genotoxic effects of rhododendron honey using three mammalian bioassays in vivo

Rhododendron honey (RH) is obtained from the rhododendron plants are grown in many regions around the world, causes poisoning in humans due to the grayanotoxin (GTX) compound in its structure. It is used by the public as a therapeutic for some diseases. It was aimed to study the genotoxic and cytotoxic effects of RH in mouse bone-marrow and sperm cells by using three mammalian bioassays. 25, 50 and 75 mg kg(-1) concentrations of RH given to male mice via gavage for 24 and 48 h treatment periods and its active ingredient Grayanatoxin (GTX-III) 0.01 mg kg(-1) by i.p. injection. Chromosome aberrations (CA), polychromatic erythrocytes (PCE)/normochromatic erythrocytes (NCE), micronucleated polychromatic erythrocytes (MNPCE) and sperm abnormalities were investigated. The results demonstrated that all the tested concentrations of RH significantly induced total abnormal cell frequency including chromosomal breaks for two time periods. In the MN assay, 75 mg kg(-1) RH and 0.01 mg kg(-1) GTX-III significantly increased % MNPCE and significantly reduced PCE/NCE ratios after 24 and 48 h treatments on mice demonstrating potential genotoxic and cytotoxic effect. Although there was a concentration-related increase in the percentage of total sperm abnormalities, this increase was not statistically significant compared to control. As a result, microscopic genotoxicity and cytotoxicity marker tests showed that RH and its active ingredient GTX-III have potential genotoxic and cytotoxic effect on mice bone marrow cells. It is understood that RH that is used to treat some diseases by public, should be handled carefully and used in a controlled manner.Duzce University Scientific Research FundDuzce University [2013.01.01.199]This study was supported by Duzce University Scientific Research Fund [Project Number= 2013.01.01.199].WOS:0006589283000012-s2.0-85107611857PubMed: 3410032

The effect of co-administration of berberine, resveratrol, and glibenclamide on xenobiotic metabolizing enzyme activities in diabetic rat liver

It is possible to use plant-derived antioxidant molecules in the form of dietary supplements. However, dietary supplement-drug interaction pattern has not been well defined for most of these products. The aim of this study was to determine the effects of berberine, resveratrol, and glibenclamide on xenobiotic metabolizing enzyme activities in diabetic rats. Streptozotocin was administered to create experimental diabetes. Resveratrol (5 mg/kg) (R), glibenclamide (5 mg/kg) (G), and berberine (10 mg/kg) (B) were administered individually or in combinations in DMSO by intraperitoneal administration route to the diabetic rats. DMSO was also given to non-diabetic control (C) and diabetic control (D) groups. Livers of rats were taken under anesthesia at the end of the treatment period (12 days). Ethoxyresorufin O-deethylase (EROD), pentoxyresorufin O-depentylase (PROD), aniline 4-hydroxylase (A4H), erythromycin N-demethylase (ERND), glutathione S-transferase (GST), catalase (CAT), and glutathione reductase (GR) activities were measured in microsomes and cytosols. In addition, histomorphological studies were also performed in the liver tissues. EROD activity of D+R was significantly higher than C and D+R+B. PROD activity of D+R was significantly higher than C, D, D+R+G, D+R+B, and D+R+B+ G. PROD activity of D+B was significantly higher than C and D+R+B. ERND activity of D+R was significantly higher than D+R+G and D+R+B. GST activity of D+R was significantly higher than D+R+G. CAT activity of D+B was significantly lower than C. It is clear that co-administration of resveratrol, berberine, and glibenclamide modifies some of the important xenobiotic metabolizing enzyme activities. Resveratrol and berberine have the potential to cause dietary supplement-drug interaction.Bolu Abant Izzet Baysal University [BAP-2015.03.03.898]This research was supported by Bolu Abant Izzet Baysal University [Project No.: BAP-2015.03.03.898].WOS:0005564674000012-s2.0-85089190247PubMed: 3276226

Decreasing myocardial estrogen receptors and antioxidant activity may be responsible for increasing ischemia- and reperfusion-induced ventricular arrhythmia in older female rats

Aims: This study aimed to investigate the relationship between ischemia- and reperfusion-induced arrhythmia and blood serum estrogen levels, myocardial estrogen receptor levels, antioxidant enzyme activities, and the effects of the estrogen receptor blocker, fulvestrant (ICI 182 780). Main methods: A total of 102 female Sprague-Dawley rats of different ages (2-3, 6-7, 14-15, and 20-21 months) were used in this study. Myocardial ischemia was produced by ligation of the descending branch of the left anterior descending coronary artery, and reperfusion was produced by releasing this artery. An electrocardiogram (ECG) and blood pressure were recorded for 6 min of ischemia and 6 min of reperfusion. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), estrogen receptor alpha (ER alpha), and estrogen receptor beta (ER beta) in myocardial tissue and 17 beta-estradiol (E2) in blood serum were measured via enzyme-linked immunosorbent assay (ELISA). The results were compared using a Mann-Whitney U test, one-way analysis of variance (ANOVA), and a student's t-test. Key findings: It is not the changes in serum estrogen levels but the decreasing myocardial estrogen receptors and antioxidant activities that could be responsible for the occurrence of more severe arrhythmia in response to reperfusion in older female rats. Significance: The death rate due to a heart attack in younger men is higher than in women. However, it equalizes after the menopausal stage in women. In this study, the reason for the increasing sudden post-menopausal death rate in women was investigated experimentally.Bolu Abant Izzet Baysal University Scientific Research Projects Coordination Unit Turkey [BAP-2016.03.01.998]This work was supported by Bolu Abant Izzet Baysal University Scientific Research Projects Coordination Unit Turkey [grant number BAP-2016.03.01.998].WOS:0006266004000272-s2.0-85100632588PubMed: 3357151

Silencing HMGB1 expression inhibits adriamycin's heart toxicity via TLR4 dependent manner through MAPK signal transduction

WOS: 000517089300076PubMed: 32277683Purpose: Adriamycin (APR) is a commonly used anti-cancer drug. ADR has toxic effects on cardiomyocytes and leads to heart failure. However, the underlying mechanism(s) by which ADR causes heart failure is still not clarified exactly. The aim of present study is to investigate whether ADR-induced heart failure is mediated via HMGB1/TLR4 to initiate the apoptosis through MAPK/AMPK pathways. Methods: H9c2 cell line was used to create four groups as a control, HMGB1 inhibition, ADR, ADR+HMGB1 inhibition. Silencing HMGB1 was performed with specific small interfering RNA. ADR was used at 2 mu M concentration for 36 and 48 hours. Protein and genes expressions, apoptosis was measured. Results: Although ADR decreased AMPK, pAMPK, ERK1/2, pERK1/2, p38, JNK protein expression, ADR+HMGB1 inhibition led to change those protein expressions. The effect of silencing of HMGB1 prevented apoptosis induced by ADR in the cells. HMGB1 caused changes a kind of posttranscriptional modification on the TLR4 receptor. This posttranscriptional modification of TLR4 receptor led to decreased AMPK protein level, but phosphorylated-AMPK. This alternation of AMPK protein caused enhancing of JNK protein, resulting from the decline of p38 and ERK protein levels. Eventually, JNK triggered apoptosis by a caspase-dependent pathway. The number of TUNEL positive and active caspase 8 cells at ADR was high, although HMGB1 silencing could decrease the cell numbers. Conclusions: Inhibition of HMGB1 might prevent the lose of the cardiac cell by inhibition of apoptotic pathway, therefore HMGB1 plays an essential role as amplifying on ADR toxicity on the heart by TLR4.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114S118]This study was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) as a Project No: 114S118

Clinical and molecular evaluation of MEFV gene variants in the Turkish population: a study by the National Genetics Consortium

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease