Investigation of apoptotic effects of Cucurbitacin D, I, and E mediated by Bax/Bcl-xL, caspase-3/9, and oxidative stress modulators in HepG2 cell line.

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.

Preventive effects of systemic Pistacia eurycarpa Yalt. administration on alveolar bone loss and oxidative stress in rats with experimental periodontitis.

OBJECTIVE: This study aimed to investigate the effects of systemic administration of P. eurycarpa Yalt. plant extract on alveolar bone loss and oxidative stress biomarkers in gingival tissue in a rat model of experimental periodontitis. METHODOLOGY: 32 male Wistar albino rats, weighing 200-250 g, were divided into four groups (n=8): Healthy control (HC), Experimental periodontitis control (EPC), Experimental periodontitis 400 mg/kg (EP400), Experimental periodontitis 800 mg/kg (EP800). Experimental periodontitis was induced using the ligating method. Distilled water was administered to the HC and EPC groups and the plant extract was administered to the EP400 and EP800 groups by oral gavage at doses of 400 mg/kg and 800 mg/kg, respectively. The rats were sacrificed on the 15th day. The values of glutathione peroxidase GSH-Px, malondialdehyde (MDA), superoxide dismustase (SOD), interleukin-1ß (IL-1ß), interleukin-10 (IL-10), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) in the gingival tissues were analyzed by ELISA tests. Alveolar bone loss was assessed using micro-CT images of the maxilla. RESULTS: Although the IL-1ß, TOS, OSI results of the healthy control group were lower than those of the other groups, the TAS values were higher (p<0.05). No significant difference was found in the biochemical parameters among the EPC, EP400, and EP800 groups (p>0.05). Alveolar bone loss was significantly reduced in the extract groups compared to the EPC group (p<0.001). CONCLUSION: Within the limitations of this study, it was observed that the systemic P. eurycarpa extract application reduced alveolar bone loss in a rat model of experimental periodontitis. Further studies are needed to elucidate the beneficial effects of P. eurycarpa.

Protective effects of vitamin E against acrylamide-induced hepatotoxicity and nephrotoxicity from fetal development to adulthood: Insights into Akt/NF-κB and Bcl-xL/Bax signaling pathways.

Acrylamide (ACR), a toxin present in fried and baked carbohydrate-rich foods, is known to cause liver and kidney damage. This study aimed to investigate the mechanisms of oxidative stress, inflammation, and apoptosis that contribute to liver and kidney damage induced by chronic administration of ACR. Additionally, the effectiveness of vitamin E in mitigating these toxic effects was examined. The study initially involved dividing 40 pregnant rats into four groups. After lactation, the research continued with male offspring rats from each group. The offspring rats were divided into Control, Vitamin E, ACR, and ACR + Vitamin E groups. Following ACR administration, liver and kidney function tests were performed on serum samples. Biochemical analyses, evaluation of inflammation markers, histopathological examination, and assessment of protein levels of Akt/IκBα/NF-κB, Bax, Bcl-xL, and Caspase-9 were conducted on liver and kidney tissues. The analysis demonstrated that ACR adversely affected liver and kidney function, resulting in oxidative stress, increased inflammation, and elevated apoptotic markers. Conversely, administration of vitamin E positively impacted these parameters, restoring them to control levels. Based on the results, the mechanism of ACR's action on oxidative stress and inflammation-induced liver and kidney damage may be associated with the activation of apoptotic markers such as Bax and Caspase-9, as well as the Akt/IκBα/NF-κB signaling pathway. Consequently, the protective properties of vitamin E establish it as an essential vitamin for the prevention or mitigation of various ACR-induced damages.

Protective role of vitamin E against acrylamide-induced testicular toxicity from pregnancy to adulthood: insights into oxidative stress and aromatase regulation.

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.

Acrylamide, Applied During Pregnancy and Postpartum Period in Offspring Rats, Significantly Disrupted Myelination by Decreasing the Levels of Myelin-Related Proteins: MBP, MAG, and MOG.

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.

Preventive effects of systemic Pistacia eurycarpa Yalt. administration on alveolar bone loss and oxidative stress in rats with experimental periodontitis

Abstract Objective: This study aimed to investigate the effects of systemic administration of P. eurycarpa Yalt. plant extract on alveolar bone loss and oxidative stress biomarkers in gingival tissue in a rat model of experimental periodontitis. Methodology: 32 male Wistar albino rats, weighing 200-250 g, were divided into four groups (n=8): Healthy control (HC), Experimental periodontitis control (EPC), Experimental periodontitis 400 mg/kg (EP400), Experimental periodontitis 800 mg/kg (EP800). Experimental periodontitis was induced using the ligating method. Distilled water was administered to the HC and EPC groups and the plant extract was administered to the EP400 and EP800 groups by oral gavage at doses of 400 mg/kg and 800 mg/kg, respectively. The rats were sacrificed on the 15th day. The values of glutathione peroxidase GSH-Px, malondialdehyde (MDA), superoxide dismustase (SOD), interleukin-1β (IL-1β), interleukin-10 (IL-10), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) in the gingival tissues were analyzed by ELISA tests. Alveolar bone loss was assessed using micro-CT images of the maxilla. Results: Although the IL-1β, TOS, OSI results of the healthy control group were lower than those of the other groups, the TAS values were higher (p<0.05). No significant difference was found in the biochemical parameters among the EPC, EP400, and EP800 groups (p>0.05). Alveolar bone loss was significantly reduced in the extract groups compared to the EPC group (p<0.001). Conclusion: Within the limitations of this study, it was observed that the systemic P. eurycarpa extract application reduced alveolar bone loss in a rat model of experimental periodontitis. Further studies are needed to elucidate the beneficial effects of P. eurycarpa.

96th-hour impact of scalding burns on end organ damage, systemic oxidative stress, and wound healing in rats treated with three different types of dressings.

In this study, we investigated the effects of three different burn dressing treatments, including experimental, silver, and modern dressing materials, on systemic oxidative stress in rats with severe scald burns within the first 96 h. The rats were divided into five groups: a burn group (n = 10), a polylactic membrane (PLM) group (n = 10), a silver sulfadiazine (SSD) group (n = 10), a curcumin group (n = 10), and a control group (n = 10), consisting of equal numbers of female and male rats. In the first four groups, 30% of the rats' total body surface area was scalded at 95°C. The burn group was not treated. Each group was treated with group-name dressing material. The control group was neither treated nor burned. The rats were sacrificed, and blood and tissue samples were obtained at the 96th hour when severe effects of oxidative stress developed postburns. Systemic inflammatory biomarkers and oxidative stress parameters were examined. In addition, apoptosis and organ damage in liver, kidney, lung, and skin tissues were evaluated biochemically and histopathologically. When the parameters were statistically analyzed, we found that systemic levels of oxidative stress and inflammatory damage to liver, kidney, and lung tissues were lower in the three treated groups than in the burn group. We believe that the dressing material's efficacy in the treatment of severe burns may be dependent on its ability to combat oxidative stress and inflammation.

Does apocynin increase liver regeneration in the partial hepatectomy model?

BACKGROUND: Hepayocyte loss may develop secondary to liver surgery and at this point liver regeneration plays a significant act in terms of liver reserve. The purpose of this research was to investigate the efficacy of apocynin on liver regeneration and preservation after partial hepatectomy in rats. METHODS: A total of 32 rats, have been divided into 4 groups (n: 8) for hepatectomy model. Inflammatory and antiinflammatory parameters were measured from blood and liver tissue samples. In addition, the effects of apocynin were examined immunohistochemically and histopathologically from liver tissue. RESULTS: In liver tissue samples, a significant difference has been found in glutathione peroxidase, total nitrite, catalase, oxidative stress index, total antioxidant and total oxidant status between sham and hepatectomy groups. A significant difference has been achieved between hepatectomy and posthepatectomy-Apocynin in terms of glutathione peroxidase and oxidative stress index. Total antioxidant status, oxidative stress index, and total oxidant status were significantly different only between the sham and the hepatectomy groups. Statistical differences were found between sham and hepatectomy groups and between hepatectomy and pre+post-hepatectomy-Apocynin groups in terms of serum glutathione, malondialdehyde, total nitrite, and L-Arginine. There were significant differences between the sham and hepatectomy groups, between hepatectomy and posthepatectomy-apocynin groups, between posthepatctomy-apocynin and pre+posthepatectomy-apocynin groups in terms of sinusoidal dilatation, intracytoplasmic vacuolization and glycogen loss (p < 0.001), in all histopathologic parameters except sinusoidal dilatation (p < 0.05). However, significant Ki-67 increases have been elaborated in hepatectomy, posthepatectomy-apocynin, and pre+posthepatectomy-apocynin groups compared to sham group (p < 0.001), in pre+posthepatectomy apocynin group compared to hepatectomy and posthepatectomy-apocynin groups (p < 0.001). DISCUSSION: Histopathology, immunohistochemistry, and biochemistry results of this study revealed that apocynin has a protective effect on enhancing liver regeneration in partial hepatectomy cases in rats.

Comparison of 'primary repair' and 'placing a drain without repair' methods in duodenum perforations.

BACKGROUND: Duodenal ulcer perforation is a serious condition. A number of methods have been defined and used in surgical treatment. In this study, it was aimed to compare the effectiveness of 'primary repair' and 'drain placement without repair' methods in duodenal perforations using an animal model. METHODS: Three equivalent groups of ten rats each were formed. Perforation was created in the duodenum in the first (primary repair/sutured group) and the second group (drain placement without repair/sutureless drainage group). In the first group, the per-foration was repaired with sutures. In the second group, only a drain was placed in the abdomen without sutures. In the third group (control group), only laparotomy was performed. Neutrophil count, sedimentation, serum C-reactive protein (CRP), serum total an-tioxidant capacity (TAC), serum total thiol, serum native thiol, and serum myeloperoxidase (MPO) analyses were performed on animal subjects in the pre-operative period and on the post-operative 1st and 7th days. Histological and immunohistochemical (transforming growth factor-beta 1 [TGF-ß1]) analyzes were performed. Blood analysis, histological, and immunohistochemical findings obtained from the groups were compared statistically. RESULTS: There was no significant difference between the first and second groups, except for the TAC on the post-operative 7th day and MPO values on the post-operative 1st day (P>0.05). Although tissue healing was more pronounced in the second group than in the first group, there was no significant difference between the groups (P>0.05). TGF-ß1 immunoreactivity observed in the second group was found to be significantly higher than in the first group (P<0.05). CONCLUSION: We think that the sutureless drainage method is as effective as the primary repair method in the treatment of duo-denal ulcer perforation and can be safely applied as an alternative to the primary repair method. However, further studies are needed to fully determine the efficacy of the sutureless drainage method.

Effects of chronic core training on serum and erythrocyte oxidative stress parameters in amputee football players.

Objective: The positive impact of aerobic exercise on blood oxidative stress parameters is well documented. However, the effect of core exercises on these parameters in amputee football players (AF) remains unclear. Therefore, this study aims to investigate the impact of core exercises on blood oxidative stress parameters in this population. Methods: Experimental method was adopted in the study. Eleven elite AF players participated in the study. The participants were divided randomly into two groups a core exercise group (CEG) and a control group (CG). Blood measurements were taken before and after the 8-week core exercise program. Blood measurements included erythrocyte Total Oxidant Status (eTOS), erythrocyte Total Antioxidant Status (eTAS), erythrocyte oxidative stress index (eOSI), serum nitric oxide (sNO), serum Total Oxidant Status (sTOS), serum Total Antioxidant Status (sTAS), serum oxidative stress index (sOSI), serum total thiol (sTT), serum native thiol (sNT), and serum disulfide (sDS) parameters were studied. Results: According to the results of the study, a significant difference was found between the 0th and eighth week pre-aerobic training load (ATL) sTOS (p = .028) values of CEG values. A significant difference was found in sTOS (p = .028) and sOSI (p = .028) values after the 0th and eighth-week pre-ATL. A significant difference was found in the sTOS (p = .043) and sOSI values (p = .043) of CG at week 0th and eighth-week pre-ATL. Conclusion: Overall, the results suggest that core exercises had a positive effect on blood oxidative stress parameters in AF players by reducing blood total oxidant levels.

Cucurbitacin E shows synergistic effect with sorafenib by inducing apoptosis in hepatocellular carcinoma cells and regulates Jak/Stat3, ERK/MAPK, PI3K/Akt/mTOR signaling pathways.

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.

Evaluation of Bone Mineral Metabolism After Liver Transplantation by Bone Mineral Densitometry and Biochemical Markers.

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.

Measurement of Heavy Metal and Antioxidant-Oxidant Levels in Tissues Obtained From Three Different Localizations of Explant Hepatectomy of Patients With Hepatocellular Carcinoma.

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.

Effects of apocynin on sciatic nerve injury in rabbits.

We investigated the effects of apocynin (APO) on experimental sciatic nerve compression injury in rabbits. We used 21 male rabbits divided randomly into three groups of seven. The control group was subjected to sciatic nerve compression with no further intervention. The APO treated group was subjected to compression injury and 20 mg/kg APO was administered daily for 21 days by intraperitoneal injection beginning the day after the injury. The sham group was treated with APO without injury. The control group exhibited shrinkage of axons, disruption of myelin sheaths and loss of nerve fibers. The damage for the control group was significantly greater than for the sham group. The severity of histopathology was decreased in the APO treated group compared to the control group, as was the oxidative stress index. Our findings suggest that APO treatment may contribute to healing of sciatic nerve damage.

Evaluation of plasma zonulin level and its relationship with inflammatory cytokines in patients with vitiligo.

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.

Evaluation of serum TWEAK, TRAIL, and oxidative stress markers in rosacea patients.

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.

Measurement of oxidant and antioxidant levels in liver tissue obtained from patients with liver transplantation: A case-control study.

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.

Tissue Heavy Metals in Liver Diseases.

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.

Cucurbitacin D Inhibits the Proliferation of HepG2 Cells and Induces Apoptosis by Modulating JAK/STAT3, PI3K/Akt/mTOR and MAPK Signaling Pathways.

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.