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AIM: This study aims to develop an experimental treatment model effective against oxidative stress in the acute period of severe burns and to analyze the mechanisms of healing large wound defects. METHODS: Five rats, including 2 females and 3 males, were used as donors to obtain adipose-derived stem cells (ADSC) from the inguinal fat pad. The stem cells were labeled with green fluorescent protein. The study included four groups of 17 rats, each with grade 3 scalding burns on 30 % of their body surface, and a control group of 10 rats with an equal number of males and females. After early excision, 106 ADSC-derived stem cells were administered subdermally to the burned wound and autografted to the stem cell group (n = 17). The early excision group (n = 17) received early excision and autograft, with 2 ml of normal saline injected subdermally into the burn wound edge. The PLM group (n = 17) was treated with a polylactic membrane (PLM) dressing after the burn. No treatment was given to the burn group (n = 17). Ten rats from all groups were sacrificed on the 4th day post-burn for oxidative stress evaluation. The control group (n = 10) was sacrificed on day 4. Blood and tissue samples were collected post-sacrifice. Oxidative stress and inflammation in the blood, as well as cell damage in the skin, liver, kidneys, and lungs, were investigated histopathologically and biochemically on the 4th day post-burn. On the 70th day after burn, wound healing was examined macroscopically and histopathologically. RESULTS: On the 4th day, oxidative stress results showed that the levels of Total Oxidative Capacity (TOC) in the blood were lowest in the stem cell (7.4 [6-8.8]), control (6.7 [5.9-7.6]), and early excision (7.5 [6.6-8.5]) groups, with no significant difference between them. The burn group (14.7 [12.5-16.9]) had the highest TOC levels. The PLM group (9.7 [8.6-10.7]) had lower TOC levels than the burn group but higher levels than the other groups. Histopathological examination on the 4th day revealed low liver caspase-3 immunoreactivity in the stem cell and early excision groups among the burn groups. Caspase-3 immunoreactivity levels were as follows: stem cell group (20 [10-30]), early excision group (25 [15-50]), PLM group (70 [50-100]), control group (0), and burn group (80 [60-120]). Other oxidative stress and end-organ damage outcomes were consistent with these results. All rats in the stem cell group had burn wounds that healed completely by the 70th day. Examination of the skin and its appendages from the stem cell group with an immunofluorescence microscope demonstrated green coloration, indicating incorporation of stem cells. CONCLUSION: Stem cells may have the potential to form new skin and its appendages, providing better healing for large skin defects. Early excision treatment, by removing local necrotic tissues after extensive and deep burns, can prevent end-organ damage due to systemic oxidative stress and inflammation. We also believe that when these two treatments are used together, they can achieve the best results.
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Cucurbitacins, natural compounds highly abundant in the Cucurbitaceae plant family, are characterized by their anticancer, anti-inflammatory, and hepatoprotective properties. These compounds have potential as therapeutic agents in the treatment of liver cancer. This study investigated the association of cucurbitacin D, I, and E (CuD, CuI, and CuE) with the caspase cascade, Bcl-2 family, and oxidative stress modulators in the HepG2 cell line. We evaluated the antiproliferative effects of CuD, CuI, and CuE using the MTT assay. We analyzed Annexin V/PI double staining, cell cycle, mitochondrial membrane potential, and wound healing assays at different doses of the three compounds. To examine the modulation of the caspase cascade, we determined the protein and gene expression levels of Bax, Bcl-xL, caspase-3, and caspase-9. We evaluated the total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), glutathione (GSH), Total, and Native Thiol levels to measure cellular redox status. CuD, CuI, and CuE suppressed the proliferation of HepG2 cells in a dose-dependent manner. The cucurbitacins induced apoptosis by increasing caspase-3, caspase-9, and Bax activity, inhibiting Bcl-xL activation, causing loss of ΔΨm, and suppressing cell migration. Furthermore, cucurbitacins modulated oxidative stress by increasing TOS levels and decreasing SOD, GSH, TAS, and total and native Thiol levels. Our findings suggest that CuD, CuI, and CuE exert apoptotic effects on the hepatocellular carcinoma cell line by regulating Bax/Bcl-xL, caspase-3/9 signaling, and causing intracellular ROS increase in HepG2 cells.
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Cucurbitacinas , Proteínas Proto-Oncogênicas c-bcl-2 , Triterpenos , Humanos , Células Hep G2 , Proteína X Associada a bcl-2 , Caspase 9/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Caspase 3/metabolismo , Cucurbitacinas/farmacologia , Estresse Oxidativo , Antioxidantes/farmacologia , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , Compostos de SulfidrilaRESUMO
Acrylamide (ACR) is a toxic chemical frequently encountered in daily life, posing health risks. This study aimed to elucidate the molecular-level mechanism of ACR's toxic effects on testicles and investigate whether Vitamin E can mitigate these effects. A total of 40 adult pregnant rats were utilized, divided into four groups: Control, ACR, Vitamin E, and ACR + Vitamin E. ACR and Vitamin E were administered to the mother rats during pregnancy and lactation, and to the male offspring until the 8th week post-birth. Serum hormone levels, oxidant-antioxidant parameters, histopathological examination of testicular tissue, and mRNA and protein levels of the testicular and liver aromatase gene were analyzed. Spermiogram analysis was conducted on the collected sperm samples from the male offspring. The results revealed that ACR exposure adversely affected hormone levels, oxidant-antioxidant parameters, histological findings, as well as aromatase gene and protein expressions. However, Vitamin E administration effectively prevented the toxic effects of ACR. These findings demonstrate that ACR application significantly impairs the reproductive performance of male offspring rats by increasing liver aromatase activity.
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Antioxidantes , Vitamina E , Gravidez , Feminino , Ratos , Masculino , Animais , Vitamina E/farmacologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Testículo , Acrilamida/toxicidade , Acrilamida/metabolismo , Aromatase/genética , Aromatase/metabolismo , Aromatase/farmacologia , Sêmen/metabolismo , Estresse Oxidativo , Oxidantes/metabolismo , Oxidantes/farmacologia , Hormônios/farmacologiaRESUMO
Dexpanthenol (DEX), a subtype of vitamin B5, plays an important role in anabolic reactions, cellular energy and regeneration in the body. Nicotine has been shown to induce kidney damage through the mechanisms of oxidative stress and apoptosis. The purpose of this study was to investigate the potential protective effects of DEX against nicotine-induced kidney damage through modulation of the AKT/Nrf2/HO-1 signaling pathway. Male rats were intraperitoneally administered with 0.5 mg/kg/day nicotine and/or 500 mg/kg/day DEX for 8 weeks. Following administration, renal function tests were conducted on serum samples, and histopathological examinations and analysis of oxidative stress markers and antioxidant enzymes were performed on tissue samples. Protein levels of Akt, Nrf-2, HO-1, Bcl-xL, and Caspase-9 were also evaluated. Nicotine administration resulted in decreased protein levels of p-Akt, Nrf-2, HO-1, and Bcl-xL and increased Caspase-9 protein levels. In addition, nicotine administration caused an increase in MDA, TOS, and OSI levels and a decrease in GSH, GSH-Px, GST, CAT, SOD, and TAS levels. Additionally, BUN and Creatinine levels increased after nicotine administration. DEX administration positively regulated these parameters and brought them closer to control levels. Nicotine-induced kidney injury caused apoptosis and oxidative stress through Caspase-9 activation. DEX effectively prevented nicotine-induced kidney damage by increasing intracellular antioxidant levels and regulating apoptosis through Bcl-xL activation. These findings suggest that DEX has potential as a protective agent against nicotine-induced kidney damage.
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Antioxidantes , Ácido Pantotênico/análogos & derivados , Proteínas Proto-Oncogênicas c-akt , Masculino , Ratos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Caspase 9/metabolismo , Caspase 9/farmacologia , Nicotina/toxicidade , Nicotina/metabolismo , Estresse Oxidativo , Apoptose , RimRESUMO
Acrylamide (ACR) is a colorless, odorless, and water-soluble solid molecule. In addition to being an important industrial material, ACR is found in fried and baked carbohydrate-rich foods. ACR is regarded as a typical axonal neurotoxin that induces neuropathy. The brain is protected from oxidative damage by vitamin E, which is regarded as the most powerful fat-soluble antioxidant vitamin. This study aimed to reveal the toxic effect of ACR on the development of myelin in the brain at the molecular level and to examine whether Vitamin E has a neuroprotective effect on the harmful effect of ACR. The study was started by dividing 40 pregnant rats into 4 groups and after lactation, the study was continued with offspring rats (females and males offspring rats) from each group. Offspring rats were equally divided into Control, Vitamin E, ACR, ACR + Vitamin E groups. Following the ACR administration, the Water Maze test was applied to evaluate cognitive function. To evaluate the level of demyelination and remyelination, MBP, MAG, and MOG proteins and mRNA levels were performed. In addition, the degeneration of myelin and glial cells was examined by immunohistochemistry and electron microscopic analysis. Analysis results showed that ACR administration decreased gene and protein levels of myelin-related proteins MBP, MAG, and MOG. The findings were confirmed by histopathological, immunohistochemical, and microscopic examinations. The application of vitamin E improved this negative effect of ACR. It has been observed that ACR may play a role in the pathogenesis of myelin-related neurodegenerative diseases by causing demyelination during gestation, lactation, and post-lactation. In addition, it has been understood that vitamin E supports myelination as a strong neuroprotective vitamin against the toxicity caused by ACR. Our research results suggest that acrylamide may play a role in the etiopathogenesis of demyelinating diseases such as multiple sclerosis in humans since fast-food-type nutrition is very common today and people are chronically exposed to acrylamide.
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Acrilamida , Doenças Desmielinizantes , Humanos , Masculino , Gravidez , Feminino , Ratos , Animais , Acrilamida/toxicidade , Bainha de Mielina , Vitamina E/farmacologia , Lactação , Vitaminas/farmacologiaRESUMO
OBJECTIVE: Cucurbitacin E (CuE), a natural compound found in medicinal plants such as Ecballium Elaterium, has demonstrated antiproliferative and apoptotic effects in various cancer cell types due to its tetracyclic triterpenoid structure. Sorafenib, a multi-tyrosine kinase inhibitor, is commonly used in hepatocellular carcinoma (HCC) treatment. This study aimed to investigate the anticancer effect of CuE alone and in combination with sorafenib on HepG2 cells. METHODS: CuE was extracted from Ecballium Elaterium fruit juice and quantitatively evaluated using HPLC. The effect of sorafenib and CuE on cell growth inhibition was determined using the MTT test. Cell cycle progression and apoptosis were assessed using flow cytometry. Mitochondrial damage was evaluated with ΔΨm, and DNA damage was assessed using the comet assay. The expression of Jak2/Stat3, PI3K/Akt/mTOR, MAPK, and Bcl-2 family-related genes and proteins were analyzed using western blot and qRT-PCR, respectively. RESULTS: Both CuE (0.1-5 µM) and sorafenib (0.5-10 µM) exhibited dose- and time-dependent antiproliferative and cytotoxic effects against the HepG2 cell line. Both compounds induced apoptosis in HepG2 cells and halted the cell cycle in the G2/M phase while causing mitochondrial and DNA damage. Both compounds down-regulated Jak2/Stat3, PI3K/Akt/mTOR, MAPK signaling pathway proteins, and Bcl-xL levels, while up-regulated Caspase-9 and Bax protein levels. CONCLUSION: Based on the results of this study, it can be concluded that CuE alone or in combination with sorafenib has the potential to be an effective therapeutic option for the treatment of HCC by inducing apoptosis and regulating multiple signaling pathways.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Triterpenos , Humanos , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Linhagem Celular Tumoral , Transdução de Sinais , Triterpenos/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Proliferação de Células , ApoptoseRESUMO
AIM: This study aimed to evaluate the course of bone and mineral metabolism after liver transplantation (LT) in patients with chronic liver disease. METHODS: One hundred four patients who had undergone LT and had a minimum of 6 months of follow-up after LT were included in this prospective cohort study. The following parameters were evaluated for each patient: preoperative and postoperative (postoperative day [POD]30, POD90, POD180) osteocalcin, bone-specific alkaline phosphatase (BALP), type 1 collagen, beta-C-terminal end telopeptide (ß-CTx), vitamin D, parathyroid hormone (PTH), ALP, calcium, phosphate, sedimentation, and bone mineral densitometer scores (L2, L4, L total, and F total). The parameters were compared in terms of sex, presence of liver tumor (hepatocellular carcinoma [HCC; n = 19] vs non-HCC [n = 85]), and presence of autoimmune liver disease (autoimmune liver disease [ALD; n = 8] vs non-ALD [n = 96]). RESULTS: The median age of the patients (n = 81 men and n = 23 women) was 52 years (95% CI, 50-56). There was a significant change in the defined time intervals in parameters such as osteocalcin (P < .001), BALP (P < .001), ß-CTx (P < .001), vitamin D (P < .001), PTH (P < .001), ALP (P = .001), calcium (P < .001), phosphate (P = .001), L2 (P = .038), L total (P = .026), and F total (P < .001) scores. There was a significant difference in POD90 ALP (P = .033), POD180 calcium (P = .011), POD180 phosphate (P = .011), preoperative sedimentation (P = .032), and POD180 F total (P = .013) scores between both sexes. There was a significant difference in POD180 osteocalcin (P = .023), POD180 ß-CTx (P = .017), and preOP calcium (P = .003) among the HCC and non-HCC groups. Furthermore, we found significant differences in preoperative ALP (P = .008), preoperative sedimentation (P = .019), POD90 (P = .037) and POD180 L2 (P = .005) scores, preoperative (P = .049) and POD180 L4 (P = .017), and POD180 L total (P = .010) and F total (P = .022) scores between the patients with and without ALD. CONCLUSION: This study shows that the bone and mineral metabolism of the LT recipients was negatively affected after LT. In addition, we showed that bone and mineral metabolism was more prominent in patients with HCC, and bone mineral density scores were higher in patients with ALD.
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Densidade Óssea , Transplante de Fígado/efeitos adversos , Biomarcadores , Fenômenos Biomecânicos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND AND STUDY AIMS: Parenteral nutrition (PN) is a life-saving practice when the use of the gastrointestinal tract is not appropriate. Despite its great benefits, however, PN may cause several complications. In this study, we conducted histopathological and ultra-structural examinations of the effect of PN combined with starvation on the small intestines of rabbits. MATERIALS AND METHODS: Rabbits were divided into four groups. A fasting + PN group was left completely unfed and received all its daily required energy by PN through an intravenous central catheter. An oral feeding + PN group received half the necessary daily calories by oral feeding and the other half through PN. A semi-starvation group received only half the necessary daily calories by oral feeding and no PN. The fourth group, serving as a control, was supplied with its entire daily energy requirements through oral feeding. After 10 days, the rabbits were euthanized. Blood and small intestine tissue samples were collected from all groups. Blood samples were biochemically analysed, and tissue samples were examined by light and transmission electron microscopy. RESULTS: The fasting + PN group exhibited lower insulin levels, higher glucose levels, and increased systemic oxidative stress than the other groups. Ultra-structural and histopathological examinations revealed a significant increase in apoptotic activity in this group's small intestines and a significant decrease in villus length and crypt depth. Severe damage to the intracellular organelles and nuclei of enterocytes was also observed. CONCLUSION: PN combined with starvation appears to cause apoptosis in the small intestine due to oxidative stress and hyperglycaemia with hypoinsulinemia, with destructive effects on small intestine tissue. Adding enteral nutrition to PN may reduce these destructive effects.
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Hiperglicemia , Nutrição Parenteral , Animais , Coelhos , Intestino Delgado , Hiperglicemia/etiologia , Estresse Oxidativo , Jejum/efeitos adversosRESUMO
BACKGROUND: To reveal any difference in terms of heavy metal and antioxidant/oxidant levels of liver tissues obtained from 3 different locations of hepatectomy specimens of patients with hepatocellular carcinoma (HCC). METHODS: Total hepatectomy materials of patients who underwent liver transplantation for HCC were objects of this study. Three liver tissue samples were obtained from each material, one from HCC tissue, one adjacent from the border of HCC, and one at least 3 cm distant from HCC, each 10 × 10 mm in diameter. Samples are preserved at -70°C. Levels of heavy metals (As, Cd, Cu, Mn, Pb, Se, and Zn) and oxidant-antioxidant parameters (catalase, glutathione peroxidase [GSHPx], superoxide dismutase [SOD], nitric oxide, prolidase, glutathione, malondialdehyde, total oxidant status, antioxidant status, oxidative stress index, total-thiol, native thiol, and disulphid) are measured. RESULTS: This study included 22 patients (18 men, 4 women with an age range of 3 to 66 years. There were significant differences in terms of Cd, Pb, Zn, GSHPx, SOD, nitric oxide, and native thiol levels between liver tissues derived from 3 different locations. Cd, Pb, and Zn levels were significantly different in tumor tissues, whereas GSHPx and SOD levels were significantly different in tumor and neighboring tissues. Nitric oxide levels were relatively different in tumor tissues compared with tumor-neighboring tissues. Native thiol levels differed significantly in tumor tissues compared with tissues distant from tumor. CONCLUSIONS: The aim of this study is unique in medical literature, which reveals that the amount of heavy metals and antioxidant/oxidant accumulation are variable in the same liver tissue in different locations because of multiple and yet unknown factors.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Metais Pesados , Masculino , Humanos , Feminino , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Antioxidantes/metabolismo , Carcinoma Hepatocelular/cirurgia , Cádmio , Oxidantes , Hepatectomia , Óxido Nítrico , Chumbo , Neoplasias Hepáticas/cirurgia , Catalase/metabolismo , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Glutationa Peroxidase/metabolismo , Compostos de SulfidrilaRESUMO
BACKGROUND: It has been proven that there is an increase in intestinal permeability in some autoimmune diseases. In our study, we purposed to assess intestinal permeability in vitiligo disease by looking at zonulin levels. At the same time, we aimed to examine the correlation of inflammatory cytokines and lipopolysaccharide (LPS) levels with zonulin. METHODS: Forty-one patients and 41 healthy participants were involved in our study. Blood samples were taken from all patients and controls, and the levels of zonulin, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and LPS were examined. RESULTS: The mean of zonulin in the patient group was found to be statistically higher than the control group (p < 0.05). A positive correlation was found between zonulin level and IL-6, TNF-α, and LPS levels (p < 0.05). TNF-α and LPS levels in the vitiligo group were significantly higher than in the control group, but there was no such significance in terms of IL-6 levels. CONCLUSION: We think that serum zonulin level increases and intestinal permeability increases in vitiligo disease.
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Citocinas , Vitiligo , Humanos , Interleucina-6 , Fator de Necrose Tumoral alfa , Vitiligo/patologia , Mucosa Intestinal/patologia , LipopolissacarídeosRESUMO
BACKGROUND: Rosacea is a chronic inflammatory skin disease of unknown pathogenesis. TWEAK and TRAIL are two cytokines thought to have a role in the pathogenesis of some inflammatory and autoimmune diseases. AIMS: The purpose of this study was to examine TWEAK and TRAIL serum levels and oxidative stress markers in patients with rosacea. MATERIAL AND METHOD: Forty rosacea patients and 40 sex- and age-matched healthy controls were involved in the study. Serum TWEAK and TRAIL levels were evaluated with ELISA kits. Serum total antioxidant status, total oxidant status, total thiol, native thiol, disulfide levels were evaluated, and oxidative stress index was computed. RESULTS: Serum levels of TWEAK, TRAIL, and oxidative stress markers did not differ statistically in the patients and controls. Both TWEAK and TRAIL levels in the patients were detected to be statistically higher in male than in female. CONCLUSION: TWEAK and TRAIL may not have a systemic effect in rosacea, unlike other inflammatory diseases. More studies are needed to investigate the role of TWEAK and TRAIL in rosacea.
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Rosácea , Humanos , Masculino , Feminino , Pele/metabolismo , Estresse Oxidativo , Citocinas , Compostos de SulfidrilaRESUMO
OBJECTIVE: This study aimed to compare oxidant and antioxidant substance accumulation in the liver tissues of patients with chronic liver disease (recipients) who underwent liver transplantation (LT) with living liver donors (LLDs) who underwent living donor hepatectomy (LDH). METHODS: This prospective study included 160 recipients (LT group) and 40 LLDs (LLD group). During surgery, a piece of liver tissue measuring a minimum of 10 × 10 mm was obtained from the edge of the right lobe of the liver of recipients and LLDs, incubated for 10 min in saline to remove blood, and stored at -70 °C until biochemical analysis was performed. Catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), myeloperoxidase (MPO), prolidase, reduced glutathione (GSH), malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), total thiol, native thiol, and disulfide levels were measured in stored liver tissues. RESULTS: There was a statistically significant difference between LT and LLD groups in terms of age (p < 0.001), body mass index (p = 0.019), GSH-Px (p < 0.001), SOD (p = 0.001), MPO (p < 0.001), prolidase (p < 0.001), GSH (p < 0.001), and MDA (p = 0.003) values in favor of the LT group. Furthermore, there was a statistically significant difference between LT and LLD groups in terms of CAT (p < 0.001), TAS (p < 0.001), TOS (p < 0.001), OSI (p < 0.001), total thiol (p < 0.001), native thiol (p < 0.001), and disulfide (p < 0.001) values in favor of the LLD group. There were no differences between the groups in terms of sex. CONCLUSION: This study demonstrated that it is possible to assess the extent of oxidative stress in liver tissues by measuring the levels of antioxidant enzymes, oxidants, or the end-products of oxidative stress. With the use of optimum and minimally invasive methods, quantifying these molecules will potentially help evaluate the extent of liver disease and prognostication of liver cirrhosis.
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Antioxidantes , Transplante de Fígado , Oxidantes , Estudos de Casos e Controles , Estudos Prospectivos , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Fígado/metabolismo , Compostos de Sulfidrila , DissulfetosRESUMO
BACKGROUND: Our objective was to determine the levels of heavy metals, oxidants, and antioxidants in liver tissue of patients with chronic liver disease (CLD) compared with healthy living liver donors (LLDs). METHODS: We obtained liver specimens from patients undergoing liver transplant for CLD. Samples were also obtained from LLDs. Biochemical analyses were performed on all samples, and the levels of liver tissue, heavy metal, and oxidant-antioxidants biomarker levels in patients with CLD were compared with those measured in LLDs. RESULTS: One hundred and eighteen individuals were included for analyses. Fifty-nine were patients with CLD, and 59 were LLDs. The median levels of liver tissue of superoxide dismutase (P = .009), glutathione peroxidase (P = .042), total oxidant status (P = .006), oxidative stress index (P < .001), and copper (P = .035) were prominently more elevated in CLD than LLDs. On the other hand, the median levels of liver tissue of cadmium (P < .001), selenium (P = .042), and zinc (P < .001) levels were more elevated in the LLDs than patients with CLD. The 2 groups were similar in terms of total antioxidant status, manganese, arsenic, and lead levels. CONCLUSIONS: Superoxide accumulation in the liver was higher in patients with CLD. Concerning heavy metals, only the median tissue copper was elevated in patients with CLD with higher Cu/Zn ratio. Cadmium, selenium, and zinc were significantly higher in the healthy LLDs.
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Hepatopatias , Metais Pesados , Selênio , Humanos , Cobre/análise , Cobre/farmacologia , Cádmio/análise , Cádmio/farmacologia , Antioxidantes/farmacologia , Selênio/farmacologia , Chumbo/farmacologia , Metais Pesados/efeitos adversos , Zinco , Fígado , Hepatopatias/diagnóstico , Hepatopatias/cirurgia , Oxidantes/farmacologiaRESUMO
Hepatocellular carcinoma is a common cancer type, especially among men. Although cucurbitacin I (CuI), widely found in plants belonging to the Ecballium elaterium (E. L) plant family, has been shown to have antitumorigenic properties in many cancer types, its anticancer effect, molecular mechanism, and apoptotic effect mediated by signal pathways on hepatocellular carcinoma have not been fully clarified. In the present study, we investigated the anticancer effect of CuI treated at different doses on the HepG2 cell line and the underlying mechanism in vitro. High-purity CuI was obtained from the E. elaterium plant with the aid of HPLC. The effects of this substance on the viability of cells were studied by the MTT assay. The effects of CuI on cell cycle progression and apoptosis were studied with flow cytometry. DNA breaks were analyzed by the Comet assay method. The proteins and genes involved in the JAK/STAT3, MAPK/ERK, and AKT/mTOR signaling pathways were investigated using Western blot and qRT-PCR, respectively. The results of this study demonstrated that CuI significantly reduced HepG2 cell growth in vitro, induced antiproliferation, and G2/M phase of the cell cycle was interrupted. PRACTICAL APPLICATIONS: CuI administration was shown to downregulate the levels of proteins in the PI3K/AKT/mTOR, MAPK, and JAK2/STAT3 cascades in HepG2 cells. CuI also reduced the expression of MAPK, STAT3, mTOR, JAK2, and Akt genes in different concentrations. DNA breaks are formed as a result of this effect. CuI, by reducing cell proliferation and promoting apoptosis, was found to have potential as a chemotherapeutic agent of hepatocellular carcinoma.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/farmacologia , TriterpenosRESUMO
BACKGROUND: Cucurbitacin D (CuD) is a natural compound that can be isolated in various plant families, mainly from Ecballium elaterium (L.) A. Rich. (E. elaterium). It is a triterpenoid with a broad spectrum of biological activity, including anti-cancer properties. Hepatocellular carcinoma, the aggressive type of liver cancer, is an important public health problem worldwide. OBJECTIVE: In the present study, we investigated the anticancer effect of CuD treated at different doses on the HepG2 cell line and the underlying mechanism in vitro. METHODS: CuD was isolated from the fruit juice of E. elaterium plant, and quantitative analysis was performed using high-performance liquid chromatography. The cell viability effect of purified CuD was determined by the MTT test, and also cell apoptosis and cell cycle arrest effects were determined by flow cytometry. DNA damage was evaluated with the comet test. Proteins and genes involved in PI3K/AKT/mTOR, MAPK, and JAK2/STAT3 signaling pathways were evaluated by western blot and qRT-PCR. RESULTS: CuD showed both antiproliferative and cytotoxic effects against the HepG2 cell line in a dose and time-dependent manner. It was observed that CuD induced apoptosis and blocked the cell cycle in HepG2 cells. It was observed that the expressions of genes and some proteins that play a key role in PI3K/AKT/mTOR, MAPK, and JAK2/STAT3 cascades were dose-dependently downregulated and led to activatation of the apoptotic pathway. CONCLUSION: All these results show promise that CuD may have a therapeutic effect in hepatocellular carcinoma.
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Carcinoma Hepatocelular , Triterpenos , Humanos , Células Hep G2 , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinoma Hepatocelular/patologia , Serina-Treonina Quinases TOR/metabolismo , Apoptose , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Transdução de Sinais , Proliferação de Células , Fator de Transcrição STAT3/metabolismoRESUMO
The aim of the present study was to investigate the therapeutic and protective effects of linalool against doxorubicin (DOX)-induced kidney injury. Forty-eight Wistar rats were divided into 8 groups as follows; Control, DOX [20 mg/kg, intraperitoneal (ip) single dose DOX], linalool (LIN50 and LIN100; 50 mg/kg and 100 mg/kg linalool via ip for 5 days, respectively), DOX + LIN50 and DOX + LIN100 (20 mg/kg single dose of DOX via ip on first day and 50 mg/kg and 100 mg/kg linalool via ip, respectively), LIN50 + DOX and LIN100 + DOX (50 mg/kg and 100 mg/kg linalool via ip for 5 days, respectively and 20 mg/kg single dose of DOX via ip on fifth day). Doxorubicin led to a significant increase in the level of malondialdehyde (MDA) in the kidney, whereas superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels decreased remarkably when compared with control. On the other hand, LIN supplementation before and after DOX treatment led to a significant decrease in MDA and also increases in SOD, CAT and GSH levels. DOX caused significant increases in the levels of blood urea nitrogen (BUN) and creatinine (Cr) levels in the plasma, while LIN supplementation as a therapeutic and preventive agent led to significant decreases in BUN and Cr levels. The current study demonstrated that LIN supplementation after or before DOX treatment can led to therapeutic and preventive effects against DOX-induced renal damage.
Assuntos
Doxorrubicina , Estresse Oxidativo , Monoterpenos Acíclicos , Animais , Antioxidantes/farmacologia , Doxorrubicina/toxicidade , Rim , Malondialdeído , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND AND AIM: The epithelial cells are the strongest determinants of the physical intestinal barrier. Tight junctions (TJs) hold the epithelial cells together and allow for selective paracellular permeability. Larazotide acetate (LA) is a synthetic octapeptide that reduces TJ permeability by blocking zonulin receptors. In this study, we aimed to investigate the effects of LA, a TJ regulator, on the liver and intestinal histology in the model of acute liver failure (ALF) in rats. MATERIALS AND METHODS: The thioacetamide (TAA) group received intraperitoneal (ip) injections of 300 mg/kg TAA for 3 days. The TAA+LA(dw) (drinking water) group received prophylactic 0.01 mg/mL LA orally for 7 days before the first dose of TAA. The LA(dw) group received 0.01 mg/mL LA orally. The TAA + LA(g) (gavage) group received prophylactic 0.01 mg/mL LA via oral gavage for 7 days before the first dose of TAA. The LA(g) group received 0.01 mg/mL LA via oral gavage. While liver tissue was evaluated only with light microscopy, intestinal samples were examined with light and electron microscopy. RESULTS: Serum ammonia, AST, and ALT levels in the TAA group were significantly higher than in control groups (all p < 0.01). Serum ALT levels in the TAA + LA(dw) group were significantly lower than in the TAA group (p < 0.05). However, serum ammonia and ALT levels did not differ between the TAA and other groups. Serious liver damage in the TAA group was accompanied by marked intestinal damage. There was no significant difference between the TAA and TAA + LA(dw) groups and TAA and TAA + LA(g) groups for liver damage scores. However, intestinal damage scores significantly decreased in the TAA + LA(dw) group compared to the TAA group. In the TAA + LA(dw) group, fusion occurred between the surface epithelial cells of neighboring villi and connecting regions formed as epithelial bridges between the villi. CONCLUSION: Our findings suggest that LA reduced intestinal damage by acting on TJs in the TAA-induced ALF model in rats.
Assuntos
Intestinos/efeitos dos fármacos , Falência Hepática Aguda/tratamento farmacológico , Fígado/efeitos dos fármacos , Oligopeptídeos/farmacologia , Junções Íntimas/efeitos dos fármacos , Animais , Masculino , Oligopeptídeos/uso terapêutico , Ratos , Ratos WistarRESUMO
INTRODUCTION: Parenteral nutrition (PN) is used for the intravenous delivery of nutrients to patients who cannot take food orally. However, it is not clear whether PN also negatively impacts cardiac tissue. The present empirical study investigated the cardiac effects of PN in rabbits. METHODS: The effects of PN were examined in three groups of rabbits: animals in the PNâ¯+â¯fasting group (nâ¯=â¯14) had been fully fasted before receiving a full PN dose via an intravenous central catheter; the PNâ¯+â¯oral feeding group (nâ¯=â¯14) received half of the daily calorie requirement as a half dose of PN via an intravenous central catheter; the third group consisted of controls (nâ¯=â¯14) with full enteral feeding and full enteral fluid intake with no PN and no central venous catheter. At the end of the 10-day study period, the rabbits were subjected to echocardiographic examination and euthanized. Blood and tissue samples were obtained from all groups. DNA was isolated from nucleated blood cells. Tissue samples were examined by both light and electron microscopy, relative telomere length was determined from DNA, and blood samples were analyzed biochemically. RESULTS: At the end of the study, there were no statistically significant differences in weight change between the three groups. Echocardiography revealed minimally impaired diastolic function in the PNâ¯+â¯fasting group compared to the other groups. Biochemical and histopathological analyses, relative telomere length determination, and electron micrographs showed significant cardiac damage in the PNâ¯+â¯fasting group but not in the PNâ¯+â¯oral feeding group or the control group. The blood biochemical analyses showed hyperglycemia and a low insulin level in the PNâ¯+â¯fasting group but not in the other two groups. CONCLUSIONS: A combination of PN and fasting may damage the cardiac muscle cells of rabbits via a mechanism involving hyperglycemia and oxidative stress. Additional enteral feeding may protect against the destructive effects of PN on cardiac tissue.
Assuntos
Cardiotoxinas , Coração/fisiopatologia , Miocárdio/patologia , Nutrição Parenteral/efeitos adversos , Animais , Hiperglicemia/etiologia , Insulina/sangue , CoelhosRESUMO
OBJECTIVES: Wilson's disease (WD) is a metabolic disorder leading to hepatic and extrahepatic copper deposition. Several studies have reported that besides copper (Cu), iron (Fe) and zinc (Zn) are also accumulated at varying levels in various tissues in WD. However, there is not an adequate number of studies investigating the effects of Fe and Zn status on WD presentation and prognosis. We aimed to evaluate serum levels of ferritin (SFr), copper (SCu), and zinc (SZn) in WD and determine their role in disease presentation and prognosis. MATERIALS-METHOD: We retrospectively reviewed the medical records of 97 pediatric patients with WD who were diagnosed and followed at Inönü University Pediatric Gastroenterology, Hepatology and Nutrition Department between January 2006 and May 2017. Serum Cu and Zn levels were analyzed by using flame atomic absorption spectrophotometer. Ferritin was analyzed by chemiluminescence immunoassay method. RESULTS: Analysis of serum levels of the elements according to the type of presentation, there was no significant difference between the groups for ceruloplasmin. However, SCU, FSCu, SFr and 24â¯h urinary copper levels were significantly higher (pâ¯=â¯0.002, pâ¯=â¯0.003, pâ¯=â¯0.023 and pâ¯<â¯0.001, respectively) and SZn and CSZn levels were significantly lower (fulminant WD). pâ¯<â¯0.001, pâ¯<â¯0.001). There was a positive correlation between SFr, SCu serum levels and mortality scores (respectively, r: 0.501, 0.564 for PELD, r:0.490, 0.504 for MELD, r: 0.345, 0.374 for Dhwan), and a negative correlation between SZn level and mortality scores. (r:-0.650 for PELD, r:-0.703 for MELD, r:-0.642 for Dhwan) We used the ROC curves to determine the worst prognosis for fulminant Wilson disease. According to these limit values, we found that the sensitivity and specificity of FWD development was significantly higher. (for SZn sensitivity of 91.5%, a specificity of 100%, p=<0,001, for SCu predicted FWD development with a sensitivity of 100%, a specificity of 73.7%, p=<0,001, for SFr predicted FWD development with a sensitivity of 92.9%, a specificity of 66.2%, pâ¯<â¯0,001) CONCLUSION: Our study suggests that SFr, SCu, SZn levels might have prognostic importance for WD.