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1.
Chem Biodivers ; 20(2): e202200704, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36703598

RESUMO

Sunitinib is a multitargeted kinase inhibitor that inhibits many receptor tyrosine kinases and has been used in the treatment of gastrointestinal stromal tumors, metastatic renal cell carcinoma, and pancreatic neuroendocrine tumors. In this study, the effects of sunitinib given to rats, both alone and after stress with cisplatin, were investigated. The animals were divided into four groups - (1) control group (C) administered interperitoneally with a single dose 0.9 % saline, (2) Cis group administered a single dose (7 mg/kg) of cisplatin, (3) Sun group administered 10 mg/kg sunitinib for seven days, and (4) Cis+Sun group administered 10 mg/kg sunitinib for seven days after a single dose (7 mg/kg) of cisplatin. After these applications, the rats were sacrificed, and blood and tissue samples were taken for biochemical and histopathological evaluations. Sunitinib did not show any effect on urea, creatine, and kidney IL1ß and TGF-ß3 expression levels when administered alone; it increased ALT, AST, and IL-38 levels. When sunitinib was given to the cisplatin-induced rats, it was observed that the increase in ALT, AST, and IL-38 levels increased more than the rats that was given only sunitinib. According to the data obtained, sunitinib does not cause a significant change in kidney tissue under both normal and stress conditions, while it creates stress in liver tissue. In addition, its toxicity in the liver becomes more certain as a result of its combination with cisplatin.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Ratos , Animais , Cisplatino/farmacologia , Sunitinibe/farmacologia , Antineoplásicos/farmacologia , Estresse Oxidativo
2.
Adv Clin Exp Med ; 32(4): 449-456, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36413179

RESUMO

BACKGROUND: Sorafenib is a multikinase inhibitor currently used in the treatment of hepatocellular carcinoma, renal cell carcinoma and thyroid cancer. OBJECTIVES: The literature on this agent is scarce. This study aimed to evaluate the effects of sorafenib when administered to both healthy and cisplatin-induced rats. MATERIAL AND METHODS: The animals were divided into 4 groups: 1) control group that received 0.9% saline intraperitoneally (C); 2) group administered a single dose (7 mg/kg) of cisplatin (Cis); 3) a group administered 20 mg/kg of sorafenib for 7 days (Sor); 4) group administered 20 mg/kg of sorafenib followed by 7 mg/kg of cisplatin for 7 days (Cis+Sor). All animals were sacrificed 7 days after the completion of their treatment arm, and serum and tissue samples were taken. RESULTS: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and interleukin 38 (IL-38) levels were increased in the Sor and Cis+Sor groups compared to the control group. When compared with the control group, serum urea, creatinine, kidney IL-1ß, and tumor necrosis factor alpha (TNF-α) levels did not change in the Sor group. When compared to the Cis group, the levels of these parameters decreased in the Cis+Sor group. CONCLUSIONS: According to the data obtained, sorafenib caused liver toxicity when given to both healthy and cisplatin-induced rats. While sorafenib did not cause any significant changes in the kidneys when given to healthy rats, it had a healing effect in kidneys after stress induced by cisplatin.


Assuntos
Cisplatino , Neoplasias Hepáticas , Ratos , Animais , Cisplatino/farmacologia , Sorafenibe/metabolismo , Sorafenibe/farmacologia , Rim/metabolismo , Antioxidantes/farmacologia , Neoplasias Hepáticas/patologia , Estresse Oxidativo
3.
Turk Kardiyol Dern Ars ; 48(6): 558-565, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32955030

RESUMO

OBJECTIVE: Coronary slow-flow phenomenon (CSFP) is defined as the delayed arrival of coronary blood flow to the distal vascular bed in at least 1 major epicardial coronary artery. Cell-free DNA (cfDNA) is a type of DNA that circulates freely in the blood once released from nucleated cells. The aim of this study was to determine if the level of cfDNA, which is an indicator of ischemia at the cellular level, was increased in CSFP. METHODS: The study included 46 patients in total: 23 patients with CSFP and 23 with a normal coronary angiogram (NCA). The level of cfDNA, and clinical, biochemical, and angiographic features of the groups were compared. RESULTS: The mean age was 53.8±10.3 years for the CSFP patient group and 56.6±9.4 years for the NCA patient group. There was no statistically significant difference between the groups in terms of basal clinical characteristics or laboratory data. The plasma cfDNA level was 5.04±2.37 ng/µL in the CSFP patients and 2.28±1.09 ng/µL in the NCA group (p<0.001). CONCLUSION: Several invasive and noninvasive studies conducted on patients with CSFP have revealed myocardial ischemia. The results of this study demonstrated that the level of cfDNA was significantly increased in patients with CSFP as a result of ischemia at the cellular level caused by microvascular disruption.


Assuntos
Ácidos Nucleicos Livres/sangue , Vasos Coronários/patologia , Isquemia/genética , Fenômeno de não Refluxo/fisiopatologia , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Angiografia Coronária/métodos , Vasos Coronários/metabolismo , Vasos Coronários/fisiopatologia , Estudos Transversais , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Isquemia/metabolismo , Isquemia/fisiopatologia , Masculino , Microvasos/fisiopatologia , Pessoa de Meia-Idade , Isquemia Miocárdica/fisiopatologia , Fenômeno de não Refluxo/diagnóstico por imagem , Estudos Prospectivos
4.
Ren Fail ; 38(6): 952-60, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27055881

RESUMO

INTRODUCTION: Patients with diabetic kidney disease (DKD) are more prone to contrast-induced nephropathy (CN). Apoptosis and autophagy were found to be essential in the pathogenesis of DKD. Interleukin-33 (IL-33) is a cytokine, but its role in DKD and CN is unknown. As IL-33 is modulated by apoptosis, we aimed to determine the relationship between IL-33 apoptosis and autophagy in DKD with CN. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were enrolled and randomly allocated into three groups. The first group was comprised of healthy rats (HRs), whereas the other two groups were made up of diabetic rats (DRs) and diabetic rats with CN (DRs + CN). All groups except the HRs received 50 mg/kg/day of streptozotocin (STZ). The DRs + CN group was induced by administering 1.5 mg/kg of intravenous radiocontrast dye on the 35th day. RESULTS: We observed increased IL-33 in the kidney tissue following induction of CN in the DRs. The DRs showed moderate immunopositivity, and the DRs + CN showed severe immunopositivity for caspase-3, cleaved caspase-3, caspase-8, caspase-9, LC3B, and Beclin-1 in tubular cells and glomeruli. The DRs also showed moderate immunopositivity in tubular cells, and the DRs + CN group showed severe immunopositivity for IL-33 in tubular cells. Increased caspase-3 was found in both glomeruli and tubuli; however, we could not demonstrate IL-33 in glomeruli. This could be secondary to inactivation of IL-33 via increased caspase-3 activity. CONCLUSION: The release of IL-33 from necrotic cells might induce autophagy, which can further balance the effects of increased apoptosis secondary to CN in DKD.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Meios de Contraste/efeitos adversos , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/tratamento farmacológico , Interleucina-33/sangue , Animais , Caspase 3/sangue , Nefropatias Diabéticas/induzido quimicamente , Rim/patologia , Glomérulos Renais/patologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Estreptozocina
5.
Pharmacol Rep ; 68(2): 378-82, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26922542

RESUMO

BACKGROUND: In this study, the effects of levosimendan used in the treatment of acute congestive heart failure upon pulmonary fibrosis in rats induced with bleomycin (BL) were analyzed. METHODS: A total of 33 male Sprague-Dawley type rats were categorized into five groups randomly. About 2.5U/kg BL was intratracheally administered to the rats in the BL, BL+L1, BL+L2, and BL+L3 groups, and 0.9% saline was intratracheally administered at the same rate to the control group. 0.3, 1, and 3mg/kg levosimendan was intraperitoneally administered to the BL+L1, BL+L2, and BL+L3 groups, respectively. Blood and tissue samples were taken from the rats euthanized to determine the changes in erythrocyte enzyme activities and to conduct histopathological evaluations after 14 days. With values between 0 and 3, histopathological scoring damage was assessed by the presence of inflammation and fibrosis in a semiquantitative manner. RESULTS: Compared with those in the C group, glutathione reductase (GR) and Catalase (CAT) enzymes decreased in the BL group; compared with that in the BL group, GR increased in the BL+L1 and BL+L3 groups, 6-phosphogluconate dehydrogenase (6PGD) increased in the BL+L3 group, and CAT increased in the BL+L2 and BL+L3 groups (p<0.05). In the histopathological evaluation, fibrosis occurred in all rats in the BL group, and tissue damage was noticed to be generally less in the BL+L1, BL+L2, and BL+L3 groups (p<0.001). CONCLUSIONS: The results obtained from biochemical and histopathological evaluations indicate that levosimendan had an anti-fibrotic effect without a dose-dependent response on pulmonary fibrosis.


Assuntos
Bleomicina/farmacologia , Hidrazonas/farmacologia , Pulmão/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Piridazinas/farmacologia , Animais , Catalase/metabolismo , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Glutationa Redutase/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Pulmão/metabolismo , Masculino , Fosfogluconato Desidrogenase/metabolismo , Fibrose Pulmonar/metabolismo , Ratos , Ratos Sprague-Dawley , Simendana
6.
J Obstet Gynaecol Res ; 42(1): 52-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26555146

RESUMO

AIM: This study investigated the effects of the antioxidant agents, ozone (O) and ellagic acid (EA), on ischemia/reperfusion (I/R) injuries developed from an ovarian torsion-detorsion model. MATERIALS AND METHODS: Arteries in the left ovaries of rats were clamped for two hours to achieve torsion, and then the clamps were removed for a two-hour detorsion period. Thirty-five female Sprague-Dawley rats were randomly divided into five groups: control: administered only with anesthesia, rats were not subjected to torsion-detorsion; I/R: subjected to torsion and subsequent detorsion, without administering any treatment agent; and I/R + EA, I/R + O and I/R + O + EA: subjected to torsion and detorsion processes and administered with EA, O or EA + O at the 75th minute of torsion. The rats were then sacrificed under general anesthesia and the ovarian tissues were excised. The tissues were homogenized and levels of glutathione reductase, catalase, superoxide dismutase and malondialdehyde (MDA) were analyzed. Tissue damage was evaluated in terms of histopathological parameters, such as hemorrhage, congestion, edema and inflammation. RESULTS: Antioxidant enzyme activity and MDA levels in the ovary tissue increased in the I/R group and decreased in the O, EA and O + EA groups (P < 0.05). Histopathological examination revealed that tissue damage in the O, EA and O + EA groups decreased in comparison with the I/R group (P < 0.05). CONCLUSIONS: These biochemical and histopathological findings suggest that EA and O are effective against ovarian I/R injury.


Assuntos
Antioxidantes/uso terapêutico , Ácido Elágico/uso terapêutico , Doenças Ovarianas/tratamento farmacológico , Ozônio/uso terapêutico , Substâncias Protetoras/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Anormalidade Torcional/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Catalase/metabolismo , Ácido Elágico/farmacologia , Feminino , Glutationa Redutase/metabolismo , Humanos , Malondialdeído/metabolismo , Doenças Ovarianas/metabolismo , Ovário/irrigação sanguínea , Ovário/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ozônio/farmacologia , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Superóxido Dismutase/metabolismo , Anormalidade Torcional/metabolismo , Resultado do Tratamento
7.
Cytotechnology ; 68(4): 979-86, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25693764

RESUMO

Bupivacaine and levobupivacaine are amino amide local anesthetics commonly used in medical practice. Although bupivacaine consists of a racemic mixture of S (-)-bupivacaine and R (+)-bupivacaine enantiomers, levobupivacaine is comprised of pure S (-)-bupivacaine. It has been known that levobupivacaine is preferable to bupivacaine since it may cause cardiovascular and nervous system toxicity. For determining genotoxicity of these anesthetics, we used the wing somatic mutation and recombination test in Drosophila melanogaster. Three-day-old trans-heterozygous larvae were treated with bupivacaine and levobupivacaine. Analysis of the standard crosses indicated that bupivacaine and levobupivacaine did not exhibit mutagenic or recombinogenic activity until toxic doses have been reached at the larval stage. When we examined bupivacaine and levobupivacaine in the HB cross, bupivacaine did not exhibit any genotoxicity at high concentrations (500 µg/mL), but levobupivacaine did exert genotoxicity at high concentrations (1000 µg/mL)-depending on the substantial recombinogenic effect.

8.
Pol J Pathol ; 66(3): 246-53, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26619103

RESUMO

Biomarkers such as mismatch repair proteins, CDX2, p53, and E-cadherin are blamed for colon cancers, but the relationships of these biomarkers with each other and with pathological risk factors in colon carcinoma are still not clear. The aim of this study was to evaluate the association of these biomarkers with each other by using immunohistochemical staining and to compare their expression with pathological risk factors for colonic adenocarcinoma. We also aimed to study the usability of a double panel of mismatch repair proteins. One hundred and eleven cases with colonic adenocarcinoma were examined. There was a statistically significant relationship between tumor histological differentiation and perineural invasion, vascular invasion, mismatch repair deficiency, p53, CDX2, and E-cadherin (p < 0.05). PMS2 and MSH6 loss covered 100% of cases with mismatch repair deficiency. Mismatch repair deficiency was correlated with CDX2 loss and E-cadherin expression (p < 0.05). It was also observed that cases with PMS2 loss covered all the cases with CDX2 loss. In conclusion, this double panel may be used instead of a quadruple panel for detecting mismatch repair deficiency. Association of CDX2 and PMS2 in the present study is necessary to conduct further genetic and pathological studies focusing on these two markers together.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/análise , Neoplasias do Colo/genética , Reparo de Erro de Pareamento de DNA/genética , Imuno-Histoquímica/métodos , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/genética , Fator de Transcrição CDX2 , Caderinas/genética , Neoplasias do Colo/patologia , Feminino , Proteínas de Homeodomínio/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteína Supressora de Tumor p53/genética
9.
Environ Toxicol Pharmacol ; 39(2): 628-34, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25682000

RESUMO

The present study evaluated the mutagenic and recombinogenic effects of two commonly used anesthetic agents, ketamine and rocuronium bromide, in medicine using the wing somatic mutation and recombination test (SMART) in Drosophila. The standard (ST) cross and the high-bioactivation (HB) cross with high sensitivity to procarcinogens and promutagens were used. The SMART test is based on the loss of heterozygosity, which occurs via various mechanisms, such as chromosome loss and deletion, half-translocation, mitotic recombination, mutation, and non-disjunction. Genetic alterations occurring in the somatic cells of the wing's imaginal discs result in mutant clones in the wing blade. Three-day-old trans-heterozygous larvae with two recessive markers, multiple wing hairs (mwh) and flare (flr(3)), were treated with ketamine and rocuronium bromide. Analysis of the ST cross indicated that ketamine exhibited genotoxicity activity and that this activity was particularly dependent on homologous mitotic recombination at concentrations of 250 µg/ml and above. Rocuronium bromide did not exert mutagenic and/or recombinogenic effects. In the HB cross, ketamine at a concentration of 1000 µg/ml and rocuronium bromide at all concentrations, with the exception of 250 µg/ml (inconclusive), exerted genotoxic effects, which could also be associated with the increase in mitotic recombination.


Assuntos
Androstanóis/toxicidade , Anestésicos/toxicidade , Drosophila melanogaster/efeitos dos fármacos , Ketamina/toxicidade , Mutagênicos/toxicidade , Animais , Drosophila melanogaster/genética , Feminino , Masculino , Testes de Mutagenicidade , Mutação , Recombinação Genética , Rocurônio , Asas de Animais
10.
Toxicol Ind Health ; 31(3): 261-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23299195

RESUMO

Mycotoxins, the toxic products of molds, exposure causes serious adverse health problems in human, animals, and crops. Determining the potential genotoxic effects of these substances is, therefore, of great importance. We have evaluated the genotoxic toxicity of two trichothecenes--diacetoxyscirpenol (DAS) and T-2 toxin--using the wing somatic mutation and recombination test (SMART) in Drosophila melanogaster. The SMART is based on the principle that the loss of heterozygosis of recessive markers located on the left arm of chromosome 3--multiple wing hairs (mwh) at the map position 0.3 and flare-3 (flr3) at the map position 38.8--may occur through various mechanisms such as mitotic recombination, mutation, deletion, half-translocation, chromosome loss, and nondisjunction. Both the mycotoxins were administered to third instar larvae (72 ± 4 h old) at concentrations ranging from 5 to 40 µM. Based on our results, DAS and T-2 toxins does not exert genotoxic effects up to a concentration of 40 µM.


Assuntos
Drosophila melanogaster/genética , Genes de Insetos/efeitos dos fármacos , Mutagênicos/toxicidade , Micotoxinas/toxicidade , Toxina T-2/toxicidade , Tricotecenos/toxicidade , Asas de Animais/efeitos dos fármacos , Animais , Dano ao DNA , Larva/efeitos dos fármacos , Testes de Mutagenicidade , Mutagênicos/química , Micotoxinas/química , Toxina T-2/química , Tricotecenos/química
11.
J Med Case Rep ; 8: 309, 2014 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-25227743

RESUMO

INTRODUCTION: Gluten enteropathy (celiac disease) is a chronic disease and presents as diarrhea, weight loss and anemia. CASE PRESENTATION: A 35-year-old Caucasian man with gluten enteropathy, familial multiple lipomas and seborrheic keratosis was seen in our clinic. After confirmation of the diagnosis, he was advised to follow a gluten-free diet. His clinical improvement was evaluated and confirmed with biopsy. CONCLUSION: Celiac disease is known to be associated with many systemic diseases and skin lesions but its association with familial multiple lipomas has not yet been reported.


Assuntos
Doença Celíaca/complicações , Doença Celíaca/dietoterapia , Dieta Livre de Glúten/métodos , Lipoma/complicações , Lipomatose/complicações , Adulto , Biópsia , Extremidades/patologia , Família , Predisposição Genética para Doença , Genitália Masculina/patologia , Humanos , Ceratose Seborreica/complicações , Ceratose Seborreica/dietoterapia , Ceratose Seborreica/patologia , Lipoma/dietoterapia , Lipomatose/dietoterapia , Lipomatose/patologia , Masculino , Resultado do Tratamento
12.
Am J Case Rep ; 15: 103-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24644527

RESUMO

PATIENT: Female, 4 FINAL DIAGNOSIS: Tumoral calcinosis Symptoms: Hard immobile mass Medication: - Clinical Procedure: - Specialty: Surgery. OBJECTIVE: Congenital defects. BACKGROUND: Tumoral calcinosis is an uncommon condition associated with the deposition of painless calcific masses. It is more common in childhood or early adolescence of African-American females. CASE REPORT: We present a case of a 4-year-old girl with tumoral calcinosis treated surgically. The case is rather rare in terms of the age of the patient and the localization of the masses (gluteal site). In our patient, the biochemical findings were normal, except for hyperphosphatemia and elevated alkaline phosphatase. CONCLUSIONS: Total excision appears to lead to a good clinical outcome and a low incidence of local relapse.

13.
Toxicol Ind Health ; 30(4): 376-83, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-22914262

RESUMO

In this study, two sulfonylureas--glimepiride and glipizide--commonly used in type 2 diabetes mellitus were investigated for genotoxicity in the Drosophila wing spot test. For this purpose, three-day-old transheterozygous larvae were treated with three mutagenic compounds, and the results obtained were compared with the control group. Mutational or recombinogenic changes were recorded in two recessive genes--multiple wing hairs (mwh) and flare (flr (3)). Two recessive markers were located on the left arm of chromosome 3, mwh in map position 0.3, and flare-3 (flr3) at 38.8, while the centromere was located in position 47.7. Wing spot tests are targeted on the loss of heterozygosity, which may be grounded in different genetic mechanisms such as mutation, mitotic recombination, deletion, half-translocation, chromosome loss, or nondisjunction. Genetic changes formatting in somatic cells of the imaginal discs cause nascence different mutant cloning in different body parts of adult flies. Our in vivo experiments demonstrated that glimepiride and glipizide show the genotoxicity, which is especially dependent on homologous somatic recombination.


Assuntos
Genes de Insetos/efeitos dos fármacos , Glipizida/toxicidade , Hipoglicemiantes/toxicidade , Mutagênicos/toxicidade , Compostos de Sulfonilureia/toxicidade , Animais , Drosophila , Proteínas de Drosophila/efeitos dos fármacos , Proteínas de Drosophila/genética , Testes de Mutagenicidade , Mutação/efeitos dos fármacos , Asas de Animais/efeitos dos fármacos
14.
Mutat Res ; 748(1-2): 17-20, 2012 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-22750076

RESUMO

This study evaluated different concentrations of selective serotonin-reuptake inhibitors (citalopram and sertraline) for genotoxicity by use of the somatic mutation and recombination test (SMART) in Drosophila melanogaster. Three-day-old larvae, trans-heterozygous for the multiple wing hairs (mwh) and flare (flr³) genes were treated with these two compounds. Two recessive markers were located on the left arm of chromosome 3, i.e. 'multiple wing hairs' (mwh) in map position 0.3 and 'flare-3' (flr³) at 38.8, while the centromere was located in position 47.7. SMART is based on the loss of heterozygosity, which may occur through various mechanisms, such as mitotic recombination, mutation, deletion, half-translocation, chromosome loss, and non-disjunction. Genetic changes occurring in somatic cells of the wing's imaginal discs, cause the formation of mutant clones on the wing blade. The results of this study show that citalopram had a genotoxic effect in the Drosophila SMART. Sertraline, however, did not show any genotoxic effect in balancer heterozygous wings. This study concluded that more information is needed to be certain regarding the mutagenic effects of sertraline.


Assuntos
Antidepressivos/toxicidade , Dano ao DNA , Drosophila melanogaster/genética , Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Inibidores Seletivos de Recaptação de Serotonina/toxicidade , Animais
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