Ekinci, Bilge; Mertoglu, Cuma; Coskun, Resit; Arslan, Yusuf Kemal; Coban, Taha Abdulkadir; Ozcicek, Fatih

Background. Cardiovascular diseases (CVDs) are highly prevalent among patients with rheumatoid arthritis (RA). Epicardial adipose tissue, serum betatrophin, chemerin, and adropin levels are factors associated with atherosclerosis and cardiovascular involvement. Objectives. This study aimed to investigate the relationship between RA and epicardial fat thickness (EFT), as well as serum betatrophin, chemerin and adropin levels. Materials and methods. This cross-sectional study included 80 patients (62 women and 18 men) diagnosed with RA according to the American College of Rheumatology/The European Alliance of Associations for Rheumatology (ACR/EULAR) 2010 RA classification criteria and 80 healthy controls (64 women and 16 men). Exclusion criteria comprised other autoimmune diseases, CVDs, diabetes mellitus, other endocrine disorders, acute or chronic pancreatic disorders, malignancy, pregnancy, breastfeeding, or antihyperlipidemic drug usage. Serum betatrophin, chemerin and adropin concentrations were measured. Epicardial fat thickness was evaluated with transthoracic echocardiography. Results. Adropin levels were significantly lower in the RA group compared to the control group (p < 0.001). Chemerin levels and EFT were significantly higher in the RA group than in the control group (p = 0.016, p < 0.001, respectively). When assessing the relationship between biomarkers and EFT in RA patients, a strong positive correlation was observed between chemerin and EFT (r = 0.73, p = 0.046) in patients with high disease activity. Conclusions. Epicardial fat thickness, as an indicator of cardiovascular involvement, is higher in patients with RA. Moreover, high chemerin levels and low adropin levels in these patients may be indicative of cardiovascular involvement. Copyright by Author(s)

Gul, Mehmet Ali; Kurt, Nezahat; Ozgeris, Fatma Betul; Yuce, Neslihan; Kocak, Omer Faruk; Parlak, Emine

Background. Coronavirus disease 19 (COVID-19) is a viral infection mediated by coronavirus-2 that causes severe acute respiratory syndrome (SARS-CoV-2). The disease may affect biochemical parameters and electrolytes. C-terminal cross-linking telopeptide (CTX-I) is released during mature bone resorption and is a biomarker for predicting bone resorption. Objectives. As the pandemic progressed, understanding the effects of COVID-19 disease remained critical. Inflammatory responses triggered by the virus can result in a bone metabolism regulation imbalance. As such, this study aimed to analyze serum levels of CTX-I, calcium (CA), phosphorus (P), magnesium (Mg), C-reactive protein (CRP), and alkaline phosphatase (ALP) in COVID-19 patients to investigate the relationship between bone resorption and the disease. Materials and methods. The study included 56 individuals with COVID-19 (divided into mild, moderate and severe subgroups depending on disease severity) and 25 healthy adults as a control group. Serum CTX-I concentrations were measured with enzyme-linked immunosorbent assay (ELISA). In addition, CRP, Ca, Mg, P, and ALP levels were measured using an automated clinical chemistry analyzer. Results. Serum CTX-I levels were significantly higher in COVID-19 patients than in the control group (p < 0.05). Furthermore, a positive weak relationship was detected between CRP and CTX-I (r = 0.303, p < 0.05). Conclusions. Increased serum CTX-I levels in the patient group caused COVID-19-driven bone degradation, though serum CTX-I levels did not differ according to disease severity.

Olmez, Hasan; Tosun, Mustafa; Unver, Edhem; Cimen, Ferda Keskin; Arslan, Yusuf Kemal; Gulaboglu, Mine; Suleyman, Bahadir

Background. Ischemia/reperfusion (I/R) can cause damage to distant organs. Rutin is known to have antioxidant and anti-inflammatory properties, and inhibits cytokine and polymorphonuclear leukocyte (PMNL) infiltration. It may prevent the development of reperfusion injury. Objectives. This study aimed to examine the role of PMNLs in distant organ (lung) injury after a liver I/R procedure, and to evaluate the protective effects of rutin in rats using biochemical and immunohistochemical methods. Materials and methods. In this study, 18 Wistar albino male rats (255–275 g) were used. Experimental animals were divided into 3 groups: a liver I/R (LIR) group, a 50 mg/kg rutin+liver I/R (RLIR) group and a sham operation (SG) control group. Experimental results obtained from the RLIR group were compared with the LIR and SG groups. Results. Blood malondialdehyde (MDA) levels in the RLIR and SG groups were significantly lower compared to the LIR group (p < 0.001). Blood myeloperoxidase (MPO) activity in the RLIR and SG groups was significantly lower compared to the LIR group (p < 0.001). Total glutathione (tGSH) levels in the RLIR and SG groups were significantly higher compared to the LIR group (p < 0.001). Conclusions. Rutin can be used to prevent distant organ (lung) damage due to liver I/R. However, more extensive studies are needed on this issue. Copyright by Author(s).

Yasar, Hasan; Altuner, Durdu; Bulut, Seval; Cicek, Betul; Gursul, Cebrail; Kuzucu, Mehmet; Suleyman, Halis

Background. Epilepsy is a severe neurological disease that results from excessive and/or synchronized neuronal activity in the brain, and oxidative stress plays a role in its pathogenesis. Taxifolin is a flavonoid that exhibits antioxidant activity. Objectives. To investigate the effects of taxifolin on caffeine-induced epileptic seizures in rats and reveal the role of antioxidant activity in antiepileptic therapy. Materials and methods. Forty rats were divided into 4 groups (n = 6/group): caffeine 300 mg/kg group (CG), taxifolin 50 mg/kg + caffeine 300 mg/kg group (TCG), 2 mg/kg diazepam + 300 mg/kg caffeine group (DCG), and a healthy group (HG). Taxifolin was given to the TCG, and diazepam was given to the DCG orally. One hour later, caffeine was injected intraperitoneally into the CG, TCG and DCG rats. The time between the caffeine injection and the contractions (the latency period) was determined. Animals were euthanized 1 h after caffeine injection, and brain tissues were biochemically examined for oxidants and antioxidants. Results. Taxifolin and diazepam prolonged the latency period to a similar extent (p = 0.549), while taxifolin was more successful in preventing mortality. Taxifolin suppressed the caffeine-induced increase in myeloperoxidase, total oxidant status and oxidative stress index, and decreased total glutathione, superoxide dismutase and total antioxidant status more effectively than diazepam (p < 0.05). Conclusions. We showed the relationship between antioxidant activity and epilepsy treatment, and demonstrated that taxifolin may be useful for treating epilepsy.

Demirtas, Levent; Gürbüzel, Mehmet; Tahirler, Hilal; Akbas, Emin Murat; Karatas, Ozhan; Arslan, Yusuf Kemal

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. Materials 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-1β, 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.

Bilici, Sami; Altuner, Durdu; Suleyman, Zeynep; Bulut, Seval; Sarigul, Cengiz; Gulaboglu, Mine; Altindag, Fikret; Ozcicek, Adalet; Gursul, Cebrail; Suleyman, Halis

Background. Favipiravir is very effective in the treatment of many viral infections, especially at high doses. It was used at such doses to treat coronavirus disease 2019 (COVID-19) during the pandemic. However, liver damage was reported in patients undergoing such treatment. Objectives. This study aimed to investigate the effects of low and high doses of favipiravir on the liver of rats, using biochemical and histopathological methods. Materials and methods. Wistar albino rats were allocated to one of 3 groups, namely a healthy group (HG), a 100 mg/kg favipiravir (FAV-100) group and a 400 mg/kg favipiravir (FAV-400) group. Favipiravir was administered orally at 100 mg/kg and 400 mg/kg doses to the FAV-100 (n = 6) and FAV-400 (n = 6) groups, respectively. Distilled water was administered orally (1 mL) using the same method to the HG (n = 6). This procedure was repeated twice a day for 1 week. At the end of this period, the animals were euthanized with a high dose of thiopental anesthesia (50 mg/kg) and their liver tissues were removed. Results. Favipiravir caused an increase in malondialdehyde (MDA), nuclear factor kappa B (NF-κB) and interleukin 6 (IL-6) levels in the liver tissue, as well as elevated alanine aminotransaminase (ALT) and aspartate aminotransferase (AST) levels in the blood. Moreover, favipiravir caused a decrease in total glutathione (tGSH), superoxide dismutase (SOD) and catalase (CAT) levels. In addition, severe edema, lymphocyte infiltration and hydropic degeneration were observed in the liver tissue of the FAV-400. Conclusions. High-dose favipiravir caused more significant oxidative and inflammatory damage in the liver tissue of rats than low-dose favipiravir.

Bedir, Zehra; Ozkaloglu Erdem, Kezban Tuna; Ates, Irem; Olmezturk Karakurt, Tulay Ceren; Gursul, Cebrail; Onk, Didem; Kurt, Nezahat; Suleyman, Zeynep; Suleyman, Halis

Background. In the literature, it has been suggested that ketamine-related oxidative organ damage results from increased blood adrenaline level, and thiopental-related oxidative damage is caused by decreased adrenaline level, suggesting that ketamine-thiopental combination (KT) may be beneficial in reducing the hepatotoxic effect of ketamine. Objectives. To biochemically investigate the effects of ketamine, thiopental and KT on the liver in rats. Materials and methods. Male albino Wistar type rats received intraperitoneally (ip.) 30 mg/kg ketamine in the ketamine alone (KG) group (n = 6), 15 mg/kg thiopental in the thiopental alone (TG) group (n = 6), and 30 mg/kg ketamine + 15 mg/kg thiopental in the ketamine+thiopental (KTG) group (n = 6). The same volume of distilled water as solvent was given to the healthy (HG) animal group. This procedure was repeated once daily for 30 days. At the end of this period, the animals were killed by decapitation and their livers were removed. In liver tissue, malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS), total antioxidant status (TAS), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin-6 (IL-6) levels were measured. The IL-1β, IL-6, TNF-α, adrenalin (ADR), noradrenalin (NDR), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were determined in blood samples taken from the tail veins. Results. In the group treated with ketamine and thiopental alone, MDA, TOS, IL-1β, IL-6, TNF-α, ADR, NDR, ALT, and AST levels were found to be high, and those of tGSH and TAS to be low. However, there was no significant change in the levels of these parameters in the KTG. Conclusions. These results indicate that oxidative stress and inflammation developed in the liver tissue of the group that used ketamine and thiopental alone, suggesting that the KT form may be safer in terms of toxicity in the clinical usage.

Alay, Murat; Sonmez, Miyase Gulcin; Sakin, Aysegul; Atmaca, Murat; Suleyman, Halis; Yazici, Gulce Naz; Coban, Abdulkadir; Suleyman, Bahadir; Bulut, Seval; Altuner, Durdu

Background. Hyperglycemia can be considered a determining factor in the development of diabetic neuropathy as well as neuropathic pain. There is a relationship between the excessive production of reactive oxygen species (ROS) and the pathogenesis of diabetic neuropathic pain. Taxifolin, on the other hand, is a flavonoid that has been documented to inhibit ROS production. Objectives. To investigate the effects of taxifolin, which has antioxidant and neuroprotective effects, on alloxan-induced hyperglycemia-induced neuropathy and neuropathic pain, biochemically and histopathologically. Materials and methods. The albino Wistar male rats were divided into 3 groups: Healthy group (HG), only alloxan group (AXG) and alloxan+taxifolin group (ATG). Hyperglycemia in animals was caused through intraperitoneal injection of alloxan at a dose of 120 mg/kg. Paw pain thresholds of animals were measured using Basile algesimeter. Sciatic nerve tissues were examined biochemically and histopathologically in order to evaluate neuropathy. Results. Our experimental results revealed that taxifolin significantly prevented the increase of plasma glucose concentration level with alloxan administration, the decrease of the paw pain threshold related to hyperglycemia, the change of oxidant-antioxidant balance in the sciatic nerve tissue in favor of oxidants, and the deterioration of tissue morphology in animals. Conclusions. Our experimental results indicate that taxifolin alleviates alloxan-induced hyperglycemia-related neuropathy and neuropathic pain.

Ozer, Mehmet; Ince, Sefa; Gundogdu, Betul; Aktas, Mehmet; Uzel, Kemine; Gursul, Cebrail; Suleyman, Halis; Suleyman, Zeynep

Background. Cyclophosphamide is a drug used in various types of cancer. It can cause oxidative and inflammatory ovarian damage and infertility. Thiamine pyrophosphate (TPP) to be investigated for its effect on cyclophosphamide-induced ovarian damage and reproductive dysfunction in the present study is the active metabolite of thiamine. It has been shown that TPP protects organs and tissues from oxidative stress and proinflammatory cytokine damage. Objectives. To investigate the effect of TPP against the ovarian damage and reproductive dysfunction caused by cyclophosphamide in rats. Materials and methods. Albino Wistar type female rats were divided into healthy control (HG), cyclophosphamide (CYC) and TPP + cyclophosphamide (TPPC) groups (for each group, n = 12). Thiamine pyrophosphate at a dose of 25 mg/kg was injected intraperitoneally (ip.) in the TPPC group, and 0.9% NaCI solution was injected ip. in the CYC and HG groups. One hour after the injection, 75 mg/kg of cyclophosphamide was administered ip. in the TPPC and CYC groups. This procedure was repeated once a day for 30 days. At the end of this period, 6 rats from each group were euthanized with a high dose of anesthetic (50 mg/kg of sodium thiopental). Biochemical and histopathological examinations were performed on the extracted ovarian tissue. The remaining animals were kept in the laboratory with mature male rats for 2 months for reproduction. Results. Thiamine pyrophosphate significantly decreased the cyclophosphamide-induced increase in the levels of the oxidant parameter malondialdehyde (MDA), proinflammatory nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β). In addition, TPP decreased the severe histopathological damage associated with cyclophosphamide in the ovarian tissue and prevented infertility. Conclusions. Our experimental results have suggested that TPP could be beneficial in the treatment of cyclophosphamide-induced ovarian injury and infertility.

Kocaturk, Hüseyin; Bedir, Fevzi; Turangezli, Ömer; Arslan, Remzi; Çoban, Taha Abdulkadir; Altuner, Durdu; Suleyman, Halis

Background. Bevacizumab-induced vascular endothelial growth factor (VEGF) inhibition may lead to a decrease in adenosine triphosphate (ATP) levels, an increase in intracellular Na+ and Ca2+ concentrations and an increase in reactive oxygen species (ROS) generation, as well as to cell damage. Objectives. To investigate the biochemical and histopathological effects of ATP, benidipine and ATP in combination with benidipine on bevacizumab-induced kidney damage in rats. Materials and methods. Rats were divided into 5 treatment groups: bevacizumab (BVZ) alone, ATP + bevacizumab (ABVZ), benidipine + bevacizumab (BBVZ), ATP + benidipine + bevacizumab (ABBVZ), and healthy controls (HC). Adenosine triphosphate (25 mg/kg), benidipine (4 mg/kg orally), ATP (25 mg/kg) + benidipine (4 mg/kg), or saline were administered to albino Wistar rats. One hour after treatment, bevacizumab was injected at a dose of 10 mg/kg to induce kidney damage. Two doses of bevacizumab were delivered 15 days apart. Adenosine triphosphate + benidipine were administered once a day for 1 month. Results. Malondialdehyde (MDA), total oxidant status (TOS), creatinine, and blood urea nitrogen (BUN) levels of the BVZ, BBVZ, ABVZ, ABBVZ, and HC groups were ranked from highest to lowest. Conversely, total glutathione (tGSH) and total antioxidant status (TAS) kidney tissue values were ranked from lowest to highest, respectively. Hemorrhage, tubular necrosis and grade 3 focal tubular atrophy were observed in the BVZ group. Atrophy and grade 2 necrosis were observed in the BBVZ group and atrophy and grade 1 necrosis were observed in the ABVZ group. Only grade 1 atrophy was observed in the ABBVZ group. Conclusions. Adenosine triphosphate reduced bevacizumab-induced renal toxicity significantly more effectively than benidipine. However, the combination of ATP + benidipine further reduced bevacizumab-induced renal toxicity relative to benidipine or ATP alone. These data indicate that ATP + benidipine might be a potential therapeutic strategy for the prevention of bevacizumab-induced renal toxicity.