Saziye Sezin Palabiyik

The protective effects of carvacrol and thymol against paracetamol-induced toxicity on human hepatocellular carcinoma cell lines (HepG2).

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.

The Role of RAAS Inhibition by Aliskiren on Paracetamol-Induced Hepatotoxicity Model in Rats.

Paracetamol is one of the most popular and widely used analgesic and antipyretic agents, but an overdose can cause hepatotoxicity and lead to acute liver failure. Aliskiren directly inhibits renin which downregulates the renin–angiotensin–aldosterone system (RAAS). Recent findings suggest that RAAS system takes part in the pathogenesis of liver fibrosis. We aimed to reveal the relationship between hepatotoxicity and the RAAS by examining paracetamol induced hepatotoxicity. Rats were separated into five groups as follows: control, 100 mg/kg aliskiren (p.o.), 2 g/kg paracetamol (per os (p.o.)), 2 g/kg paracetamol + 50mg/kg aliskiren (p.o.), and 2 g/kg paracetamol + 100 mg/kg aliskiren(p.o.). Samples were analyzed at the biochemical, molecular, and histopathological levels. Paracetamol toxicity increased alanine aminotransferases (ALT), aspartate aminotransferases (AST), renin, and angiotensin II levels in the serum samples. In addition, the SOD activity and glutathione (GSH) levels decreased while Lipid Peroxidation (MDA) levels increased in the livers of the rats treated with paracetamol. Paracetamol toxicity caused a significant increase in TNF‐α and TGF‐β. Both aliskiren doses showed an improvement in ALT, AST, oxidative parameters, angiotensin II, and inflammatory cytokines. Only renin levels increased in aliskiren treatment groups due to its pharmacological effect. A histopathological examination of the liver showed that aliskiren administration ameliorated the paracetamol‐induced liver damage. In immunohistochemical staining, the expression of TNF‐α in the cytoplasm of the hepatocytes was increased in the paracetamol group but not in other treatment groups when compared to the control group. In light of these observations, we suggest that the therapeutic administration of aliskiren prevented oxidative stress and cytokine changes and also protected liver tissues during paracetamol toxicity by inhibiting the RAAS. J. Cell. Biochem. 117: 638–646, 2016.

The Role of Urotensin Receptors in the Paracetamol-Induced Hepatotoxicity Model in Mice: Ameliorative Potential of Urotensin II Antagonist

We aimed to evaluate the possible protective effect of a UTR antagonist and to determine the effect of the antagonist on ALT and AST levels in serum, the mRNA expression level of UTR, tumour necrosis factor‐alpha (TNF‐α) and IL‐1β and SOD activity, GSH and MDA levels in liver tissues, which are important mediators or markers for the hepatotoxicity animal model in mice. Animals fasted overnight and were divided into seven equal groups (n = 12). The first group was the healthy group (administered 0.1% DMSO intraperitoneally). Group 2 received only paracetamol (PARA) (administered orally at a dosage of 300 mg/kg). Groups 3 and 4 were treated with only AGO (AC7954, UTR agonist) 15 and 30 mg/kg intraperitoneally, respectively. Groups 5 and 6 were treated with only ANTA (SB657510, UTR antagonist) 30 and 60 mg/kg intraperitoneally, respectively. Group 7 was treated with AGO 30 mg/kg and ANTA 60 mg/kg intraperitoneally. One hour after the pre‐treatment drugs were administered, groups 3 through 7 were given PARA. After the experimental period, the mice were killed 6 and 24 hr after PARA was administered. Antagonist administration significantly decreased the ALT and AST levels, while agonist administration did not. In addition, SOD activity and GSH levels increased, and the MDA level decreased with the pre‐treatment of two antagonist doses. The increased UTR gene expression through PARA was significantly lower in both doses of the antagonist groups at 24 hr when compared with the agonist and PARA groups. This study showed that UTR antagonists have hepatoprotective and anti‐inflammatory effects on high‐dose PARA‐induced hepatotoxicity in mice.

Study of the boron levels in serum after implantation of different ratios nano-hexagonal boron nitride-hydroxy apatite in rat femurs.

Boron and its derivatives are effective in bone recovery and osteointegration. However, increasing the boron levels in body liquids may cause toxicity. The aim of our study is to investigate serum boron levels using ICP-MS after implantation of different ratios of nano-hBN-HA composites in rat femurs. All rats were (n=126) divided into five experimental groups (n=24) and one healthy group (6 rats); healthy (Group1), femoral defect + %100 HA (Group2), femoral defect + %2.5 hBN + %97.5 HA (Group3), femoral defect + %5 hBN + %95 HA (Group4), femoral defect + %10 hBN + %90 HA (Group5), femoral defect + %100 hBN (Group6). The femoral defect was created in the distal femur (3mm drill-bit). Each implant group was divided into four different groups (n=24) also 6 rats sacrificed for each groups in one week intervals during four weeks. In our results; at 1, 2, 3, and 4 weeks after implantation near bone tissue, serum levels of boron were evaluated using ICP-MS. We demonstrated that neither short-term nor long-term implantation of hBN-HA composite resulted in statistically increased serum boron levels in experimental groups compared to healthy group. In conclusion, this study investigated the implant material produced form hBN-HA for the first time. Our data suggest that hBN is a new promising target for biomaterial and implant bioengineers.

A new update for radiocontrast-induced nephropathy aggravated with glycerol in rats: the protective potential of epigallocatechin-3-gallate

Abstract Contrast media (CM) is known to have nephrotoxic adverse effects. Epigallocatechin-3-gallate (EGCG) is the most abundant and active catechin in green tea, and has strong antioxidant and anti-inflammatory properties. This study investigated whether EGCG can reduce contrast-induced nephrotoxicity (CIN), alone or with glycerol (GLY)-induced renal damage, and to understand its mechanisms of protection against toxicity, using models of GLY and CIN in rats. The rats were separated into eight groups (n = 6 in each), as follows: Healthy, GLY, CM, GLY + CM, CM + EGCG 50 mg/kg (po), GLY + CM + EGCG 50 mg/kg (po), CM + EGCG 100 mg/kg (po), and GLY + CM + EGCG 100 mg/kg (po). Both doses of EGCG protected against CM-induced renal dysfunction, as measured by serum creatinine and blood urea nitrogen (BUN). In addition, EGCG treatment markedly improved CIN-induced oxidative stress, and resulted in a significant down-regulatory effect on tumor necrosis factor (TNF)-α and nuclear factor (NF)-κB mRNA expression. Moreover, histopathological analysis showed that EGCG also attenuated CM-induced kidney damage. Considering the potential clinical use of CM and the numerous health benefits of EGCG, this study showed the protective role of multi-dose EGCG treatment on CIN and GLY-aggravated CIN through different mechanisms.

Endothelial dysfunction biomarker, endothelial cell-specific molecule-1, and pediatric metabolic syndrome

The aim of this study was to compare serum endothelial cell‐specific molecule‐1 (endocan) in pediatric patients with metabolic syndrome (MetS) and in healthy children, and to determine whether it can be used as an indicator of endothelium damage‐induced complications in pediatric MetS patients.

Levels of endothelial cell-specific molecule-1 (ESM-1) in overt hypothyroidisim

ABSTRACT Purpose: Endothelial cell-specific molecule-1, endocan, is a proteoglycan that is expressed by the vascular endothelium. Endocan can be a biomarker of endothelial dysfunction caused by endothelial cell-dependent disorders. Endothelial dysfunction is an early step of atherosclerosis and is developed in hypothyroid patients, which indicates an association between hypothyroidism and atherosclerosis. Therefore, we aimed to investigate whether circulating endocan levels are associated with endothelial dysfunction in overt hypothyroid patients. Materials and methods: Forty patients with hypothyroidism diagnosed in the last 5 years and 30 healthy subjects were recruited. Results: The mean endocan value in all patients was 0.63 ± 0.26 pg/ml, which was higher than that in controls (0.36 ± 0.10 pg/ml, p < 0.05). When we subgrouped the patients as hypothyroid and euthyroid, all groups demonstrated significantly different endocan levels, and hypothyroid patients had the highest endocan levels. A correlation analysis demonstrated that endocan levels were positively correlated with body mass index (BMI), thyroid-stimulating hormone (TSH), anti-thyroid peroxidase, and anti-thyroglobulin and negatively correlated with free thyroid hormone 4 (FT4) and vitamin D levels. In addition, in the patient group, endocan levels were correlated with FT4 levels independently in a covariance analysis. Conclusions: The circulating endocan level increased in hypothyroid patients, suggesting that endocan levels may be an early biomarker of the development of endothelial dysfunction in patients with hypothyroidism. They may also prove useful in the prediction of cardiovascular diseases after further studies using cardiovascular disease biomarkers. In addition, targeting endocan levels to decrease cardiovascular risk may be a new treatment strategy in these patients.

Endothelial dysfunction biomarker, endothelial cell-specific molecule-1, and pediatric metabolic syndrome: Endocan in pediatric MetS

The aim of this study was to compare serum endothelial cell‐specific molecule‐1 (endocan) in pediatric patients with metabolic syndrome (MetS) and in healthy children, and to determine whether it can be used as an indicator of endothelium damage‐induced complications in pediatric MetS patients.

An endothelial dysfunction biomarker, ENDOCAN, and its link with pediatric metabolic syndrome.

The aim of this study was to compare serum endothelial cell‐specific molecule‐1 (endocan) in pediatric patients with metabolic syndrome (MetS) and in healthy children, and to determine whether it can be used as an indicator of endothelium damage‐induced complications in pediatric MetS patients.