Effects of vitamin D on kidney histology and trpv1 channels in doxorubicin-induced nephropathy.

Doxorubicin (DXR) is an antineoplastic agent of the anthracycline group, and may show nephrotoxic effects in animal models and humans. We investigated changes in kidney tissue following doxorubicin treatment and the effects of vitamin D on kidney tissue and TRPV1 channels. In this study, 24 adult male Wistar Albino rats were used. The animals were divided into four groups of six animals. During the 14-day experiment period, Group I did not have any application. 200 IU/day cholecalciferol was administered orally to Group II. Group III received 10 mg/kg single dose of DXR intraperitoneally (IP); and Group IV had a single 10 mg/kg dose of IP DXR and 200 IU/day of oral cholecalciferol. At the end of the experiment, the rats were decapitated, and their kidney tissues were removed. TRPV1 expression and apoptosis were detected in the tissue section by using immunohistochemical, TUNEL and real time-PCR (RT-PCR) techniques. The findings were examined and photographed with BH2 Olympus photomicroscope. As result of immunohistochemical staining, RT-PCR and examination with light microscope, it was found that the TRPV 1 immunoreactivity of the DXR group decreased in comparison with the control group, and the vitamin D application did not reverse this effect. Apoptosis detected by the TUNEL method tended to increase in the doxorubicin group and was relatively reversed with the administration of vitamin D. Tissue malondialdehyde (MDA) levels were observed to correlate with the findings of apoptosis. This study showed that vitamin D has anti- apoptotic and antioxidant effects on kidney tissue after DXR-induced injury.

Relationships between plasma pentraxin 3 levels and inflammation markers patients with tunneled permanent catheter in hemodialysis.

PURPOSE: Vascular access (VA) devices may contribute to chronic inflammation in hemodialysis (HD). Pentraxin 3 (PTX3) is a recently discovered acute phase protein that responds more rapidly than other inflammatory markers. This study compared PTX3 and other markers between HD patients and healthy controls. METHODS: The study population included 30 patients with tunneled permanent catheter (TPC), 30 patients with arteriovenous fistula (AVF) and 30 healthy controls. Hemogram, biochemical assays, ferritin, high sensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and PTX3 were evaluated in all groups. RESULTS: PTX levels were highest in HD patients with TPC, intermediated in HD patients with AVF and lowest in healthy controls (5.2 + 2.4 vs. 3.1 + 1.3 vs. 1.8 + 0.7, p<0.001 for all comparisons). PTX3 levels correlated strongly to hs-CRP (r = 0.857) and moderately to TNF-α, NLR, ferritin and total neutrophil count. PTX3 and albumin levels had a negative correlation. PTX3 levels were higher in patients with 8 months of TPC than those with 7 months or less. CONCLUSIONS: PTX3 levels are significantly elevated in all patients on HD, but presence and extended duration of TPC are associated with incrementally higher levels of PTX3 and other inflammatory markers. PTX3 and NLR may be useful in assessing chronic inflammatory states in HD.

Effect of enalapril maleate on ghrelin levels in metabolic syndrome in rats.

We have explored how enalapril affects ghrelin levels in serum and renal tissues of rats with fructose-induced MetS, using 5-week-old Wistar albino male rats weighing 220 ± 20 g. They divided into 5 groups: (i) control (CT), no fructose supplement fed on standard rat pellet and tap water for 60 days, (ii) metabolic syndrome (MetS) fed with 10% fructose for 60 days, (iii) rats after metabolic syndrome developed treated with enalapril over 30 days (MetS+E30), (iv) rats in which only enalapril was administered for 60 days (E60), and (v) MetS-treated with enalapril for 60 days (MetS+E60). Enalapril maleate was given at 20mg/kg per day by gavage. Fasting serum insulin, uric acid, triglyceride, low-density lipoprotein cholesterol and total cholesterol levels were significantly higher, and the amount of high density lipoprotein cholesterol, and acylated and desacyl ghrelin levels was significantly lower in the MetS groups. Ghrelins were significantly lower in all 3 groups, which were administered enalapril than that of MetS and the control group. Immunohistochemical staining showed that the density of ghrelin was parallel to the serum levels of the peptide. Ghrelin immunoreactivity in the kidneys was of moderate density in the distal and collecting tubules, mild density in the proximal tubule and glomeruli, whereas the density decreased in the MetS group and other enalapril-treated groups. In conclusion, ghrelin levels in MetS groups were significantly lower than control group, and thus Enalapril treatment improves components of MetS and has direct effects on serum ghrelin levels that are independent of MetS.

The renoprotective effect of curcumin in cisplatin-induced nephrotoxicity.

The polyphenol curcumin has several pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer features. In this study, we evaluated the effects of curcumin in cisplatin-induced nephrotoxicity in rats. Male Wistar rats were divided into four groups: (1) control; (2) cisplatin (7 mg/kg body weight, intraperitoneal as a single dose); (3) curcumin (100 mg/kg via gavage, for 10 days); and (4) cisplatin and curcumin. The cisplatin-treated rats exhibited kidney injury manifested by increased serum urea and creatinine (p<0.05). The kidney tissue from the cisplatin treated rats also exhibited a significant increase in the malondialdehyde (MDA) levels (p<0.05). The treatment with curcumin prevented a rise in the serum urea, creatinine and MDA levels when compared to the control group kidneys (p<0.05). The analysis the nicotinamide phosphoribosyltransferase (NAMPT) and sirtuin (SIRT) proteins (SIRT1, SIRT3 and SIRT4), which play important roles in the resistance to stress and the modulation of the threshold of cell death, showed similar trends (p<0.05). In the cisplatin-only treated rats, the induced renal injury decreased the levels of the NAMPT and SIRT proteins. Conversely, the curcumin increased the levels of the NAMPT and SIRT proteins in the cisplatin-treated rats (p<0.05). These data suggest that curcumin can potentially be used to reduce chemotherapy-induced nephrotoxicity, thereby enhancing the therapeutic window of cisplatin.

Can serum NGAL levels be used as an inflammation marker on hemodialysis patients with permanent catheter?

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a member of lipocalin family and released from many tissues and cells. We aimed to investigate the relationship among serum NGAL levels, the inflammation markers (IL-6, hs-CRP, TNF-α) and different vascular access types used in dialysis patients. METHODS: The study population included 90 patients and 30 healthy age-matched controls. The patients were divided into three groups (I, II, III) and group IV included the controls. In group I and II, the patients were with central venous permanent catheter and arterio-venous fistula, respectively. Group III included 30 patients with chronic renal failure. Hemogram, biochemical assays, ferritin, IL-6, hs-CRP, TNF-α, and NGAL were evaluated in all groups. RESULTS: Serum NGAL levels were markedly higher in group I than in group II (7645.80 ± 924.61 vs. 4131.20 ± 609.87 pg/mL; p < 0.05). Positive correlation was detected between NGAL levels and duration of catheter (r: 0.903, p: 0.000), hs-CRP (r: 0.796, p: 0.000), IL-6 (r: 0.687, p: 0.000), TNF-α (r: 0.568, p: 0.000) levels and ferritin (r: 0.318, p: 0.001), whereas NGAL levels were negatively correlated with serum albumin levels (r: -0.494, p: 0.000). In multiple regression analysis, duration of catheter hs-CRP and TNF-α were predictors of NGAL in hemodialysis patients. CONCLUSION: Inflammation was observed in hemodialysis patients and increases with catheter. Our findings show that a strong relationship among serum NGAL levels, duration of catheter, hs-CRP and TNF-α. NGAL may be used as a new inflammation marker in hemodialysis patients.

Chromium picolinate and chromium histidinate protects against renal dysfunction by modulation of NF-κB pathway in high-fat diet fed and Streptozotocin-induced diabetic rats.

BACKGROUND: Diabetic nephropathy is one of major complications of diabetes mellitus. Although chromium is an essential element for carbohydrate and lipid metabolism, its effects on diabetic nephropathy are not well understood. The present study was conducted to investigate the effects of chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-κB) and nuclear factor-E2-related factor-2 (Nrf2) pathway in the rat kidney. METHODS: Male Wistar rats were divided into six groups. Group I received a standard diet (8% fat) and served as a control; Group II was fed with a standard diet and received CrPic; Group III was fed with a standard diet and received CrHis; Group IV received a high fat diet (HFD, 40% fat) for 2 weeks and then were injected with streptozotocin (STZ) (HFD/STZ); Group V was treated as group IV (HFD/STZ) but supplemented with CrPic for 12 weeks. Group VI was treated as group IV (HFD/STZ) but supplemented with CrHis. RESULTS: The increased NF-κß p65 in the HFD/STZ group was inhibited by CrPic and CrHis supplementation (P < 0.05). In STZ-treated rats, a significant decrease in levels of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) was found in kidney tissues when compared to control rats (P < 0.05). A significant increase in the levels of IκBα was observed in CrPic- and CrHis-treated rats when compared with STZ-treated rats. Renal Nrf2 levels were significantly decreased in diabetic rats compared with the control rats. There was a higher tendency for increase of kidney Nrf2 level and decrease in kidney NFκBp65 levels and 4- hydroxyl nonenal (4-HNE) protein adducts (P < 0.05) in diabetic rats. CONCLUSION: Our result show that in kidney tissue CrHis/CrPic increases Nrf2 level, parallelly decreases NF-κB and partially restores IκBα levels in HFD/STZ group, suggesting that CrPic and CrHis may play a role in antioxidant defense system via the Nrf2 pathway by reducing inflammation through NF-κß p65 inhibition. Moreover, a greater reduction in NF-κB expression and greater increases in expressions of IκBα and Nrf2 in diabetic rats supplemented with CrHis than rats supplemented with CrPic suggest that CrHis has more favorable effects than CrPic.

The effect of strict volume control on cognitive functions in chronic hemodialysis patients.

Cognitive dysfunction is a well-known complication of chronic renal failure that is evident in 30% of hemodialysis (HD) patients. However, the pathogenesis of this dysfunction is unknown. Left ventricular hypertrophy could develop in hypertensive HD patients without establishing normovolemia. Our aim was to evaluate the effect of strict volume control by salt restriction and ultrafiltration on cognitive functions in HD patients. This cross-sectional study was composed of 22 HD patients who were normotensive by applying a strict volume control, 24 HD patients who were normotensive by receiving anti-hypertensive drugs, and 20 healthy controls. The strict volume control was defined as managing of blood pressure control by strict salt restriction and insistent ultrafiltration. P300 recording as an indicator of cognitive disfunction was measured when blood pressures were reached at target level at the end of six-month follow-up period. In all patients, dimensions of the heart were evaluated with echocardiography on an interdialytic day. The cardiothoracic ratio and echocardiographic dimensions were significantly lower in patients with strict volume control. P300 amplitudes were significantly lower in patients on antihypertensive drugs than in patients with strict volume control (9.5 +/- 5.1 versus 11.3 +/- 5.4 muV). P300 latency was longer in patients on antihypertensive drugs than in the control group and patients with strict volume control (359.9 +/- 39.6 versus 345.6 +/- 36.7 ms). Our results suggest that hypervolemia may be one of the causal and potentially modifiable factors of cognitive dysfunction. Strict volume control may have beneficial effects on cognitive functions in hemodialysis patients.

The effects of trimetazidine on lipid peroxidation in patients with end-stage renal disease.

It is known that the increase in levels of free oxygen radicals is important in the development of complications related to end-stage renal disease (ESRD). This study investigated plasma malondialdehyde (MDA) levels as a marker of lipid peroxidation (LPO), and the effects of trimetazidine (TMZ), which is known to have antioxidant activity, on LPO. The study registered 16 hemodialysis patients, 16 continuous ambulatory peritoneal dialysis (CAPD) patients and 24 healthy individuals. The patients were given TMZ 60 mg/day divided into three doses for 6 months. Plasma MDA levels were significantly higher in both patient groups before the treatment compared to the controls (P<0.001). MDA levels after treatment with TMZ declined (from 1.94+/-0.58 nmol/ml to 0.73+/-0.35 nmol/ml; P<0.001) in the hemodialysis group and (from 1.51+/-0.32 nmol/ml to 0.50+/-0.17 nmol/ml; P<0.001) in the CAPD group. In this study it was found that oxidative stress markedly increased in both dialysis groups, and TMZ treatment reduced the increased production of oxygen radicals. We believe that TMZ can prevent the effects of increased oxidative stress through its systemic antioxidant effects and may also be useful for the treatment of cardiovascular complications, the major cause of mortality in ESRD.

Serum paraoxonase and arylesterase activities in patients with lung cancer in a Turkish population.

BACKGROUND: Lung cancer (LC) is the leading cause of cancer-related deaths. Oxidative DNA damage may contribute to the cancer risk. The antioxidant paraoxonase (PON1) is an endogenous free radical scavenger in the human body. The aim of this study was to determine serum PON1 and arylesterase (ARE) activities in patients with newly diagnosed LC. METHODS: This case control study involved a total of 39 patients with newly diagnosed LC (untreated) and same number of age- and sex-matched healthy individuals. Serum PON1 and ARE activities in addition to lipid parameters were measured in both groups. RESULTS: Serum PON1 and ARE activities were found to be lower in patients with LC compared to the controls (p = 0.001 and p = 0.018, respectively). The ratio of PON1/high density lipoprotein (HDL) was significantly lower in the LC group compared to the control one (p = 0.009). There were positive correlations between the serum levels of HDL and PON1 in both the control (r = 0.415, p = 0.009) and the LC groups (r = 0.496, p = 0.001), respectively. PON1 enzyme activity was calculated as three different phenotypes in both groups. In regard to lipid parameters, total cholesterol levels were significantly lower (p = 0.014) in the LC group whereas the other lipid parameters such as HDL, LDL, and triglyceride levels were not significantly different among groups. CONCLUSION: Serum PON1 activity is significantly low in the LC group compared with the healthy controls. Metastasis status and cigarette smoking do not affect serum PON1 activity in the LC patients.

Gabapentin-induced coma in a patient with renal failure.

We describe a 60-year-old woman who became comatose after a single dose of gabapentin for right-sided sciatalgia. The patient was improved by hemodialysis. Gabapentin toxicity should be considered when mental status changes develop in patients with renal failure after even a single dose.