Admis, Ozlem; Yavuzer, Bulent; Mammadov, Renad; Suleyman, Bahadir; Altuner, Durdu; Mendil, Ali Sefa; Yucel, Nurinisa; Suleyman, Halis

Linezolid, an oxazolidinone antibiotic effective against Gram-positive pathogens, may cause nephrotoxicity and lactic acidosis during prolonged therapy. This experimental study investigated the protective effects of adenosine triphosphate (ATP), thiamin, thiamin pyrophosphate (TPP), and their combination (ATTP) on linezolid-induced renal injury and lactic acidosis in rats. Thirty-six male Wistar rats were randomly divided into six groups (n = 6): healthy control (HG), linezolid only (LZD), ATP+linezolid (ATLZD), thiamin + linezolid (TLZD), TPP+linezolid (TPLZD), and ATP+thiamin + TPP+linezolid (ATTPL). Linezolid (125 mg/kg, orally) was administered twice daily, while ATP (4 mg/kg), thiamin (20 mg/kg), and TPP (20 mg/kg) were given intraperitoneally once daily for 28 days. At the end of treatment, kidney tissues were examined for oxidative stress markers [malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT)] and histopathology, and blood samples were analyzed for blood urea nitrogen (BUN), creatinine, and lactate. Linezolid increased oxidative stress, suppressed antioxidants, and elevated BUN, creatinine, and lactate levels. ATP partially improved the oxidative balance in renal tissue but failed to prevent hyperlactatemia and impaired renal function. Thiamin did not produce significant changes. TPP markedly improved oxidative stress markers and reduced renal dysfunction. The triple combination provided the most pronounced protection, restoring antioxidant defenses, kidney function, and lactate levels to near-control values. Histopathological evaluation revealed marked tubular degeneration, interstitial hemorrhage, and mononuclear cell infiltration in the linezolid group, which were markedly improved by TPP and combination therapy. These findings indicate that TPP protects against linezolid-induced nephrotoxicity and lactic acidosis, with its efficacy further enhanced by ATP.

Kocaturk, Huseyin; Bedir, Fevzi; Altay, Mehmet Sefa; Bakan, Ebubekir; Suleyman, Bahadir; Yazici, Gulce Naz; Sunar, Mukadder; Suleyman, Zeynep; Suleyman, Halis

Purpose: To examine the effect of desloratadine on kidney ischemia-reperfusion (I/R) injury in albino Wistar male rats using biochemical and histopathological methods. Methods: The treated with ischemia–reperfusion + 5 mg/kg desloratadine (IRD) group (n–6) was given 5 mg/kg desloratadine by gavage orally, and applied renal ischemia-reperfusion (BIR) group (n–6) and control (SG) group undergoing Sham operation (n–6) rats were given distilled water as solvent one hour before ketamine anesthesia. During the anesthesia period, ischemia was induced for 2 h unilaterally in the left kidney of all rats followed by reperfusion for 6 h. The kidneys of the SG group had sham operation without any intervention. Results: Our biochemical test results showed that malondialdehyde (MDA), nuclear factor kappa (NF-κB), tumor necrosis factor alpha (TNF-α), interleukin one beta (IL-1β), creatinine, and blood urea nitrogen (BUN) levels were significantly increased in the BIR group compared to the healthy control and IRD groups treated with desloratadine. Histopathological results were revealed tubular dilatation, tubular necrosis, loss of brushy margins, cast formation, and apoptotic bodies in tubular epithelial cells in the BIR group. There were no histopathological findings except for the swelling of tubule epithelial cells and the accumulation of proteinous material in some tubule lumens in renal tissue of desloratadine-treated rats. Conclusions: Experimental results suggested that desloratadine may be useful in the treatment of renal I/R injury.

Palabiyik, Saziye Sezin; Dincer, Busra; Cadirci, Elif; Cinar, Irfan; Gundogdu, Cemal; Polat, Beyzagul; Yayla, Muhammed; Halici, Zekai

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 50mg/kg (po), GLY+CM+EGCG 50mg/kg (po), CM+EGCG 100mg/kg (po), and GLY+CM+EGCG 100mg/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.

Demirtas, Levent; Turkmen, Kultigin; Kandemir, Fatih Mehmet; Ozkaraca, Mustafa; Kucukler, Sefa; Gürbüzel, Mehmet; Comaklı, Selim

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

Güçlü, Aydin; Yonguç, Nilüfer; Dodurga, Yavuz; Gündoʇdu, Gülşah; Güçlü, Zuhal; Yonguç, Tarik; Adigüzel, Esat; Turkmen, Kultigin

Background: Diabetic nephropathy is the most common cause of end-stage renal disease. Emerging evidences indicate that many mechanistic pathways including apoptosis play an important role in the pathogenesis and progression of macrovascular and microvascular complications of diabetes mellitus. The aim of the present study is to show the effects of grape seed extract (GSE) on oxidative stress and apoptosis in the kidney of streptozotocin-induced diabetic rats. Materials and methods: The study included control group, diabetic group without treatment and diabetic group treated with GSE (n=7) group. GSE was given orally (100 mg/kg/day) for six weeks. Following parameters were evaluated; oxidative stress index, caspase 1, IL1-alpha, caspase 2, IL1-beta, BCL2-associated agonist of cell death (BAD), X-linked inhibitor of apoptosis (XIAP), DNA fragmentation factor, alpha subunit and beta bubunit (DFFA, DFFB), BH3 interacting domain death agonist (BID), caspase 6, Bcl2-like 1 (BCL-XL), caspase 8, tumor necrosis factor receptor superfamily, member 1 b (TNFRSF1B) and IAP-binding mitochondrial protein (DIABLO). Results: Oxidative stress index levels were significantly increased in the kidney of diabetic group without treatment compared to control group, and decreased in diabetic + GSE group compared to diabetic group without treatment. In the kidney of diabetic group without treatment, caspase 1, IL-1 alpha, BAD, DFFA, DFFB and caspase-6 gene expressions were significantly higher compared to control group. In diabetic + GSE group caspase 1, caspase 2, XIAP, DFFA, BID, BCL-XL and TNFRSF1B genes were significantly decreased compared to control group. Conclusions: Grape seed reduces oxidative stress and apoptosis gene expression suggesting the protective effect on diabetic nephropathy.

Turkmen, Kultigin; Guney, Ibrahim; Yazici, Raziye; Arslan, Sevket; Altintepe, Lutfullah; Yeksan, Mehdi

Introduction: Impairment of health-related quality of life (HRQoL) and being in a depressive mood were found to be associated with increased mortality in peritoneal dialysis (PD) patients. We aimed to investigate the association between HRQoL, depression, other factors and mortality in PD patients. Materials and methods: Totally 171 PD patients were included and followed for 7 years in this prospective study. Results: Of 171 PD patients, 45 (26.3%) deceased, 18 (10.5%) maintained on PD, 87 (50.9%) shifted to hemodialysis (HD) and 21 (12.3%) underwent transplantation. The most common cause of death was cardiovascular disease (32, 71.1%) followed by infection (6, 13.3%), cerebrovascular accident (5, 11.2%). The etiology of patients who shifted to HD was PD failure (41, 47.1%), peritonitis (33, 37.9%), leakage (6, 6.9%), catheter dysfunction (3, 3.4%), self willingness (4, 4.6%). Non-survivors were older than survivors (56.6 ± 15.0 vs. 43.6 ± 14.6, p = 0.003). There were also statistically significant difference in terms of albumin, residual urine, presence of diabetes and co-morbidity. When the groups were compared regarding HRQoL scores, non-survivors had lower physical functioning (p < 0.001), role-physical (p = 0.0045), general health (p = 0.004), role-emotional (p = 0.011), physical component scale (PCS) (p = 0.004), mental component scale (MCS) (p = 0.029). Age, presence of residual urine, diabetes, albumin, PCS and MCS were entered in regression analysis. Decrease of 1 g/dL of albumin and being diabetic were found to be the independent predictors of mortality. Conclusions: Diabetes and hypoalbuminemia but not HRQOL scores were associated with higher mortality in PD patients after 7 years of following period.

Erdur, Mehmet Fatih; Tonbul, Halil Zeki; Ozbiner, Huseyin; Ozcicek, Adalet; Ozcicek, Fatih; Akbas, Emin Murat; Ozbek, Orhan; Hamur, Hikmet; Turkmen, Kultigin

Introduction: Epicardial adipose tissue (EAT) is the true visceral fat depot of the heart. The relationship between coronary artery disease and EAT was shown in end-stage renal disease (ESRD) patients. One of the established risk factor in this population is dyslipidemia. We aimed to determine the relationship between atherogenic index of plasma (AIP) and EAT in ESRD patients. Methods: This was a cross-sectional study involving 76 ESRD patients receiving PD or HD for ≥6 months and 42 healthy subjects. EAT was measured by using an electrocardiogram-gated 64-multidetector computed tomography (MDCT). Atherogenic index of plasma was calculated as the logarithmically transformed ratio of the serum trigliseride to HDL-cholesterol. Results: The etiology of ESRD patients was diabetic nephropathy (n = 16), chronic glomerulonephritis (n = 10), hypertensive nephropathy (n = 23), polycystic kidney disease (n = 7), nephrolithiasis (n = 5) and unknown (n = 15). There were no differences with respect to the following variables between ESRD patients and healthy subjects: age; sex; BMI; predialysis levels of DBP; serum levels of albumin, HDL-cholesterol and hemoglobin. However, ESRD patients had higher serum levels of trigliseride, hs-CRP and AIP when compared to healthy subjects. There was a statistically significant relationship between EAT, BMI and AIP in ESRD patients (r = 0.42, p < 0.001 and r = 0.25, p = 0.028, respectively). The stepwise linear regression analysis revealed that age, as well as BMI were independent predictors of EAT. Conclusion: We found a relationship between EAT as defined by MDCT and AIP in ESRD patients. Further clinical and experimental studies are needed.