Protective Effect of Royal Jelly and Green Tea Extracts Effect Against Cisplatin-Induced Nephrotoxicity in Mice: A Comparative Study

Kürşad Yapar,Kültiğin Çavuşoğlu,Ertan Oruç,Emine Yalçin 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.5

The aim of the present study was to investigate the protective role of royal jelly (RJ) and green tea (GT) extracts on cisplatin (cDDP)-induced nephrotoxicity in adult albino mice. Albino mice were randomly divided into six groups: Group I (control) received a single intraperitoneal injection of isotonic saline (0.02mL/g), Group II received a single intraperitoneal injection of cDDP (7mg/kg of body weight), Group III received RJ (100mg/kg of body weight), Group IV received GT (100mg/kg of body weight), Group V received RJ (100mg/kg of body weight)+cDDP (7mg/kg of body weight), and Group VI received GT (100mg/kg of body weight)+cDDP (7mg/kg of body weight). The concentrations of blood urea nitrogen (BUN) and creatinine were evaluated. In addition, kidney samples were taken for determination of tissue malondialdehyde (MDA) and reduced glutathione (GSH) levels. In addition, histopathological changes in kidneys were investigated. The results indicated that no significant differences in MDA, GSH, BUN, and creatinine levels were observed among the control group and groups treated with RJ alone and GT alone (P>.05). However, there was a significant increase in BUN and creatinine parameters after cDDP application in Groups II, V, and VI. The mice treated with only cDDP exhibited an increase in serum BUN and creatinine levels when compared to Groups V and VI (P<.05). Moreover, cDDP-induced oxidative damage caused a significant decrease in GSH levels and a significant increase in MDA levels in kidneys (P<.05). RJ and GT supplementation attenuated cDDP-induced nephrotoxicity, which was manifested by stopping the elevation in serum creatinine and BUN levels. Moreover, RJ and GT supplementation restored GSH content and MDA production levels in the kidney tissue following cDDP treatment (P<.05). These products were also effective in protecting against cDDP-induced tissue damage in mouse kidneys. In conclusion, 100mg/kg of body weight doses of RJ and GT provided protection against cDDP-induced nephrotoxicity, and both products can act as protector agents against cDDP-induced kidney damages.

Protective Role of Ginkgo biloba Against Hepatotoxicity and Nephrotoxicity in Uranium-Treated Mice

Kürşad Yapar,Ku¨ ltig˘in C¸ avus¸og˘lu,Ertan Oruc,Emine Yalc¸in 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.1

The aim of the present study was to investigate the protective role of Ginkgo biloba leaf extract against uranium (U)-induced toxicity in Swiss albino mice. The mice were randomly divided into six groups, each consisting of six animals: Group I (control) received tap water alone, Group II received U at a dose of 5mg/kg of body weight, Group III received G. biloba at a dose of 50mg/kg of body weight, Group IV received G. biloba at a dose of 150mg/kg of body weight, Group V received G. biloba (50mg/kg of body weight) and U (5mg/kg of body weight), and Group VI received G. biloba (150mg/kg of body weight) and U (5mg/kg of body weight) by oral gavage for 5 days. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine levels were determined to assess liver and kidney function, respectively. Also, liver and kidney samples were taken for the determination of tissue malondialdehyde (MDA) and reduced glutathione (GSH) levels, and histopathological changes in liver and kidneys were investigated. The results indicated that there was a significant increase (P<.05) in selected serum parameters. Serum AST, ALT, BUN, and creatinine levels significantly increased in mice treated with U alone when compared to the other groups. Moreover, U-induced oxidative damage caused a significant decrease in GSH levels and a significant increase in MDA levels of liver and kidney tissues. Treatment with G. biloba produced amelioration in biochemical indices of hepatotoxicity and nephrotoxicity according to Group II. Each dose of G. biloba provided significant protection against U-induced toxicity, and its strongest effect was observed at a dose of 150mg/kg of body weight. In vivo results showed that G. biloba extract is a potent protector against U-induced toxicity, and its protective role is dose-dependent.

The Protective Effect of Royal Jelly on Chronic Lambda-Cyhalothrin Toxicity: Serum Biochemical Parameters, Lipid Peroxidation, and Genotoxic and Histopathological Alterations in Swiss Albino Mice

Kültiğin Çavuşoğlu,Kürşad Yapar,Ertan Oruç,Emine Yalçın 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.10

The present study was undertaken to investigate the protective effect of royal jelly (RJ) against toxicity induced by a synthetic pyrethroid insecticide, lambda-cyhalothrin (LCT), in Swiss albino mice. Animals were randomly divided into six groups of six animals each. The control group received distilled water alone, whereas mice in the treatment groups received RJ alone (100 or 250 mg/kg of body weight), LCT alone (668 ppm), or RJ+LCT for 21 days. All mice (100%) survived until the end of experiment and were sacrificed at the end of 24 hours. Blood, bone marrow, and liver and kidney tissues were analyzed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and reduced glutathione (GSH) levels and micronucleus (MN) frequency, chromosomal aberrations (CAs), and pathological damages. Serum AST, ALT, BUN, and creatinine levels were elevated in mice treated with LCT alone compared with the other tested groups (P<.05). LCT-induced oxidative damage caused a significant decrease in GSH levels and a significant rise in MDA levels of liver and kidney tissues. LCT alone–treated mice presented higher frequencies (P<.05) of MNs, CAs, and abnormal metaphases compared with the controls; moreover, the mitotic index was lower than in controls (P<.05). Oral treatment with RJ significantly ameliorated the indices of hepatotoxicity, nephrotoxicity, lipid peroxidation, and genotoxicity induced by LCT. Both doses of RJ tested provided significant protection against LCT-induced toxicity, and its strongest effect was observed at the dose level of 250 mg/kg of body weight. In vivo results suggest that RJ is a potent antioxidant against LCT-induced toxicity, and its protective effect is dose dependent.

Protective Effect of Ginkgo biloba L. Leaf Extract Against Glyphosate Toxicity in Swiss Albino Mice

Kültiğin Çavuşoğlu,Kürşad Yapar,Ertan Oruç,Emine Yalçın 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.10

The aim of the present study was to investigate the protective role of Ginkgo biloba L. leaf extract against the active agent of Roundup^ⓡ herbicide (Monsanto, Creve Coeur, MO, USA). The Swiss Albino mice were randomly divided into six groups, with each group consisting of six animals: Group I (control) received an intraperitoneal injection of dimethyl sulfoxide (0.2 mL, once only), Group II received glyphosate at a dose of 50 mg/kg of body weight, Group III received G. biloba at a dose of 50 mg/kg of body weight, Group IV received G. biloba at a dose of 150 mg/kg of body weight, Group V received G. biloba (50 mg/kg of body weight) and glyphosate (50 mg/kg of body weight), and Group VI received G. biloba (150 mg/kg of body weight) and glyphosate (50 mg/kg of body weight). The single dose of glyphosate was given intraperitoneally. Animals from all the groups were sacrificed at the end of 72 hours, and their blood, bone marrow, and liver and kidney tissues were analyzed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and glutathione (GSH) levels and the presence of micronucleus (MN), chromosomal aberrations (CAs), and pathological damages. The results indicated that serum AST, ALT, BUN, and creatinine levels significantly increased in mice treated with glyphosate alone compared with the other groups (P<.05). Besides, glyphosate-induced oxidative damage caused a significant decrease in GSH levels and a significant increase in MDA levels of the liver and kidney tissues. Moreover, glyphosate alone–treated mice presented higher frequencies of CAs, MNs, and abnormal metaphases compared with the controls (P<.05). These mice also displayed a lower mean mitotic index than the controls (P<.05). Treatment with G. biloba produced amelioration in indices of hepatotoxicity, nephrotoxicity, lipid peroxidation, and genotoxicity relative to Group II. Each dose of G. biloba provided significant protection against glyphosate-induced toxicity, and the strongest effect was observed at a dose of 150 mg/kg of body weight. Thus, in vivo results showed that G. biloba extract is a potent protector against glyphosate-induced toxicity, and its protective role is dose-dependent.

Royal Jelly (Honey Bee) Is a Potential Antioxidant Against Cadmium-Induced Genotoxicity and Oxidative Stress in Albino Mice

Kültiğin Çavuşoğlu,Kürşad Yapar,Emine Yalçin 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.6

Cadmium (Cd) is a highly toxic heavy metal that induces genotoxic damage in the body. Besides, Cd induces oxidative damage in various tissues by altering antioxidant defence enzymes system. In this study, we investigated the protective role of royal jelly (RJ) on Cd-induced genotoxicity and oxidative stress in mice. For this aim, the micronucleus (MN) test in erythrocytes and exfoliated cells of buccal mucosa and the chromosome aberration (CA) test in bone marrow cells were applied. In addition, the levels of reduced glutathione (GSH) and malondialdehyde (MDA) were evaluated in the liver and kidneys. Thirty-six animals were divided into six groups: the control group received distilled water alone, whereas mice in the treatment groups received RJ alone (100 and 250mg/kg of body weight), Cd alone (2mg/kg of body weight), and RJ+Cd. Cd toxicity resulted in a significant (P<.05) increase in CAs, abnormal metaphase number, and MN formation. Cd also caused a decrease in mitotic index. Oral administration of RJ at two doses (100 and 250mg/kg of body weight) showed significant (P<.05) suppression of mutagenic effects of Cd. Moreover, Cd-induced oxidative damage caused a significant decrease in GSH level and a significant increase in MDA level in the liver and kidneys. Treatment with two doses of RJ caused a significant recovery in antioxidant status of GSH and a significant inhibition of MDA production. It could be concluded that RJ has a protective role against Cd-induced genotoxicity and oxidative stress in mice, due to its antioxidant effects.

Protective Role of Grape Seed Extract Against Doxorubicin-Induced Cardiotoxicity and Genotoxicity in Albino Mice

Emine Yalçin,Ertan Oruç,Kültiğin Çavuşoğlu,Kürşad Yapar 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.4

In this study, the protective role of grape seed extract (GSE) against doxorubicin (DOX)-induced cardiotoxicity and genotoxicity has been evaluated in male Mus musculus var. albino mice. The micronucleus (MN) test in erythrocytes and the chromosome aberration (CA) test in bone marrow cells were used. Also, levels of reduced glutathione (GSH) and lipid peroxidation as malondialdehyde (MDA) in heart homogenates were measured, and in addition the changes in heart histology were investigated. The mice were randomly divided into six groups. Group I (negative control) received intraperitoneal injections of isotonic saline (0.02mL/g) for 6 consecutive days, Group II received intraperitoneal injections of DOX (2.5mg/kg of body weight, six doses every other day; cumulative dosage, 15mg/kg of body weight) for 6 consecutive days, Group III received GSE (50mg/kg of body weight, 21 doses every other day; cumulative dosage, 1,050mg/kg of body weight) for 21 consecutive days, Group IV received GSE (150mg/kg of body weight, 21 doses every other day; cumulative dosage, 3,150mg/kg of body weight) for 21 consecutive days, Group V received GSE (50mg/kg of body weight, 28 doses every other day; cumulative dosage, 1,400mg/kg of body weight) for 28 consecutive days plus DOX (2.5mg/kg of body weight, six doses every other day; cumulative dosage, 15mg/kg of body weight) for 6 consecutive days, and Group VI received GSE (150mg/kg of body weight, 28 doses every other day; cumulative dosage, 4,200mg/kg of body weight) for 28 consecutive days plus DOX (2.5mg/kg of body weight, six doses every other day; cumulative dosage, 15mg/kg of body weight) for 6 consecutive days. DOX induced heart damage as indicated from a pronounced change in heart histology. In the DOX-treated group, there was a significant increase in MDA content in the heart homogenate, and the level of GSH was significantly decreased. DOX induced genotoxicity by increasing the number of aberrant metaphases (AMNs), MNs, and structural chromosomal aberrations (CAs) such as chromatid breaks, dicentrics, acentric fragments, and gaps and showed a detractive effect on the mitotic index (MI) of cells. Pretreatment with GSE before treatment with DOX significantly protected the heart tissue by ameliorating its antioxidant activity. In Groups V and VI, the MDA level of heart tissue was significantly decreased, and the GSH level was increased compared to the DOX-treated group. Moreover, GSE significantly protected bone marrow chromosomes from DOX-induced genotoxicity by reducing the total AMNs and the frequency of structural CAs. GSE treatment also decreased the frequency of MNs and increased the MI values. It could be concluded that GSE acts as a potent antioxidant to prevent heart damage and genotoxicity of bone marrow cells.

Long-term outcomes of cervical cancer patients with complete metabolic response after definitive chemoradiotherapy

Cem Onal,Ozan Cem Guler,Mehmet Reyhan,Ali Fuat Yapar 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.5

Objective: We investigated the importance of metabolic parameters measured with18 F-fluorodeoxyglucose positron-emission tomography integrated with computed tomography (FDG-PET/CT) for predicting progression-free survival (PFS) and overall survival (OS) in cervical cancer with complete metabolic response (CMR) after chemoradiotherapy (ChRT). Methods: The clinical data and PET parameters including standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of 122 patients having CMR in post-treatment 18F-FDG-PET/CT delivered a median of 3.9 months after ChRT completion were analyzed. Results: With a median follow-up of 8.4 years, 55 patients (45%) presented with disease a median of 19.7 months after ChRT. For SUVp, MTVp, TLGp, SUVln, MTVln, and TLGp, the cut- off values for OS determined by receiver operating curve analysis were 15.8, 48.7 cm3, 552.3, 8.7, 7.0 cm3, respectively. All metabolic PET parameters were significant prognostic factors for OS and PFS in univariate analysis. International Federation of Gynecology and Obstetrics (FIGO) stage was predictive of both OS and PFS, while pelvic and/or para-aortic lymph node metastasis were predictive of OS only. In multivariate analysis, FIGO stage ≥IIB, MTVp ≥49.8 cm3, and TLGp ≥597.4 were predictive of worse OS. Advanced stage, presence of lymph node metastasis, higher TLGp, and larger MTVln were significant factors for poor PFS rates. Conclusion: We found that advanced stage and higher TLGp values were significant predictors for poor survival and higher progression rates. Volumetric PET parameters could be used to predict treatment outcomes in patients with CMR after definitive ChRT.

Multiplex Real-Time PCR Method for Simultaneous Identification and Toxigenic Type Characterization of Clostridium difficile From Stool Samples

Abdullah Kilic,Mohammad J. Alam,Naradah L. Tisdel,Dhara N. Shah,Mehmet Yapar,Todd M. Lasco,Kevin W. Garey 대한진단검사의학회 2015 Annals of Laboratory Medicine Vol.35 No.3

Background: The aim of this study was to develop and validate a multiplex real-time PCR assay for simultaneous identification and toxigenic type characterization of Clostridium difficile. Methods: The multiplex real-time PCR assay targeted and simultaneously detected triose phosphate isomerase (tpi) and binary toxin (cdtA) genes, and toxin A (tcdA) and B (tcdB) genes in the first and sec tubes, respectively. The results of multiplex real-time PCR were compared to those of the BD GeneOhm Cdiff assay, targeting the tcdB gene alone. The toxigenic culture was used as the reference, where toxin genes were detected by multiplex real-time PCR. Results: A total of 351 stool samples from consecutive patients were included in the study. Fifty-five stool samples (15.6%) were determined to be positive for the presence of C. difficile by using multiplex real-time PCR. Of these, 48 (87.2%) were toxigenic (46 tcdA and tcdB-positive, two positive for only tcdB) and 11 (22.9%) were cdtA-positive. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the multiplex real-time PCR compared with the toxigenic culture were 95.6%, 98.6%, 91.6%, and 99.3%, respectively. The analytical sensitivity of the multiplex real-time PCR assay was determined to be 103colonyforming unit (CFU)/g spiked stool sample and 0.0625 pg genomic DNA from culture. Analytical specificity determined by using 15 enteric and non-clostridial reference strains was 100%. Conclusions: The multiplex real-time PCR assay accurately detected C. difficile isolates from diarrheal stool samples and characterized its toxin genes in a single PCR run.

Adult Urological Soft Tissue Sarcomas: A Multicenter Study of the Anatolian Society of Medical Oncology (ASMO)

Unal, Olcun Umit,Oztop, Ilhan,Menekse, Serkan,Urakci, Zuhat,Bozkurt, Oktay,Ozcelik, Melike,Gunaydin, Yusuf,Yasar, Nurgul,Yazilitas, Dogan,Kodaz, Hilmi,Taskoylu, Burcu Yapar,Aksoy, Asude,Demirci, Umut Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.11

Objective: To analyze clinicopathological characteristics, prognostic factors and survival rates of the patients with urological soft tissue sarcomas treated and followed up in Turkey. Materials and Methods: For overall survival analyses the Kaplan-Meier method was used. From medical records, nine prognostic factors on overall survival were analysed. Results: For the 53 patients (34 males, 19 females) whose charts were reviewed, the median age was 53 (range 22 to 83) years. Most frequently renal location (n=30; 56.6%) was evident and leiomyosarcoma (n=20, 37.7%) was the most frequently encountered histological type. Median survival time of all patients was 40.3 (95% CI, 14.2-66.3) months. In univariate analysis, male gender, advanced age (${\geq}50years$), metastatic stage, unresectability, grade 3, renal location were determined as worse prognostic factors. In multivariate analysis, metastatic stage, unresectability and grade 3 were determined as indicators of worse prognosis. Conclusions: Urological soft tissue sarcomas are rarely seen tumours in adults. The most important factors in survival are surgical resection, stage of the tumour at onset, grade and location of the tumour, gender and age of the patients.