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Nurhan Sahin,
Fatih Akdemir,
Cemal Orhan,
Abdullah Aslan,
Can A Agca, Hasan Gencoglu,
Mustafa Ulas,
Mehmet Tuzcu,
Juturu Viyaja,
James R Komorowskı,
Kazim Sahin
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ABSTRACT: Aims: A novel nutritional supplement complex (N21 #125) composed of four well-known compounds (chromium picolinate, phosphatidylserine, docosahexaenoic acid, and boron) was designed to improve memory function and maintain brain health. The present study evaluated the complex's potential mechanism of action and its role in reducing oxidative stress in the brain of obese rats fed a high-fat diet (HFD). Methods: Male Wistar rats (n = 40, 8-week-old) were divided into four groups. Group I was fed a standard diet; Group II was fed a standard diet and supplemented with N21 #125; Group III was fed an HFD; and Group IV was fed an HFD and supplemented with N21 #125 for 12 weeks. Results: Rats fed HFD had greater serum C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-α) and brain malondialdehyde (MDA) concentrations than rats fed the control diet. Supplementation of N21 #125 decreased CRP, TNF-α, and MDA concentration in rats fed HFD. The levels of brain nuclear factor-E2-related factor-2 (Nrf2), heme oxygenase, extracellular signal-regulated kinases and protein kinase B were lower in rats fed the control diet than for rats fed the HFD. These parameters were increased by supplementation of N21 #125. Discussion: The data indicate that N21 #125 protected the brain from oxidative damage and inflammation induced by the HFD. This effect may be through up-regulation of the transcription factor Nrf2 expression.
Nutritional Neuroscience 09/2012; 15(5):42-47. · 1.56 Impact Factor
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ABSTRACT: Context: Lycopene is a carotenoid found in tomato, watermelon, pink grapefruit, and guava in high concentration. Dietary intake of lycopene has been proposed to inversely correlate with the risk of cancer. It has also been reported to provide protection against cellular damage caused by reactive oxygen species, which makes it worthwhile to study the effect of lycopene on liver damage in rat model. Objective: In this study, we report the effect of lycopene on 7,12-dimethylbenz[a]-anthracene (DMBA)-induced expression of Bax, Bcl-2, caspases, and oxidative stres biomarkers in the liver. Materials and methods: Lycopene was administered orally at 20 mg/kg body weight for 20 weeks followed by the intraperitoneal injection of DMBA (50 mg/kg body weight) on day 1 and day 30 of the experiment. Control rats received vehicle (olive oil) or DMBA alone. Rats were sacrificed after completion of the treatment. Results: We observed that the levels of Bax, caspase-3, and caspase-9 decreased to 44, 67, and 43%, respectively, and Bcl-2 increased by 80% in DMBA-treated rats. Lycopene reversed the changes in the respective groups, and decreased the level of Bcl-2 to 25%, while increasing the Bax to 42% when compared to DMBA control. Lycopene increased the expression of caspase-3 (82.09%) and caspase-9 (58.96%), and attenuated the level of hepatic malondialdehyde (41%) and 8-isoprostane (40%) when compared to the respective controls. Glutathione (GSH) decreased significantly in DMBA group (15.89%), but reached the normal level in lycopene-treated animals. Hepatic lycopene concentration in treated rats was 8.2 nmol/g tissue. Conclusion: The study reports that lycopene counteracts the hepatic response to DMBA by altering the expression of Bax, Bcl-2, caspases, and oxidative stress biomarkers in animal model.
Pharmaceutical Biology 09/2012; 50(12):1513-1518. · 0.88 Impact Factor
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ABSTRACT: The objective of this experiment was to investigate the effects of supplemental chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-κB p65) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway in diabetic rat brain. Nondiabetic (n = 45) and diabetic (n = 45) male Wistar rats were either not supplemented or supplemented with CrPic or CrHis via drinking water to consume 8 μg elemental chromium (Cr) per day for 12 weeks. Diabetes was induced by streptozotocin injection (40 mg/kg i.p., for 2 weeks) and maintained by high-fat feeding (40 %). Diabetes was associated with increases in cerebral NF-κB and 4-hydroxynonenal (4-HNE) protein adducts and decreased in cerebral nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha (IκBα) and Nrf2 levels. Both Cr chelates were effective to decrease levels of NF-κB and 4-HNE protein adducts and to increase levels of IκBα and Nrf2 in the brain of diabetic rats. However, responses of these increases and decreases were more notable when Cr was supplemented as CrHis than as CrPic. In conclusion, Cr may play a protective role in cerebral antioxidant defense system in diabetic subjects via the Nrf2 pathway by reducing inflammation through NF-κB p65 inhibition. Histidinate form of Cr was superior to picolinate form of Cr in reducing NF-κB expression and increasing Nrf2 expression in the brain of diabetic rats.
Biological trace element research 07/2012; · 1.92 Impact Factor
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ABSTRACT: In previous studies, we have demonstrated the biological activity of thymoquinone (TQ), an active compound extracted from the Nigella sativa plant, against cisplatin-induced neurotoxicity. Recenty, it was observed that there is an inherent lack in regulation of renal organic anion and cation transporters in cisplatin-induced nephrotoxicity. Here, we report, for the first time, the effect of TQ on alterations in the renal expression of organic anion transporters (OATs) and organic cation transporters (OCTs), as well as multidrug resistance-associated proteins (MRPs) in rats treated with cisplatin. Twenty-eight 8-week-old male Wistar rats were divided into four groups of control, TQ treated (10 mg/kg b.w. in drinking water for 5 days), cisplatin (7 mg/kg b.w., i.p.) and TQ and cisplatin combination treatment. Cisplatin-induced malondialdehyde (MDA) and 8-isoprostane increase was found to be markedly reduced in rats treated with TQ. In cisplatin only treated rats, the induced renal injury increased protein levels of the efflux transporters MRP2 and MRP4 while expression of OAT1, OAT3, OCT1 and OCT2 was reduced. In combination TQ- and cisplatin-treated rats, expression of MRP2 and MRP4 proteins was decreased in the kidneys. Conversely, TQ treatment increased levels of OCT1, OCT2, OAT1 and OAT3 and decreased levels of 8-isoprostane and MDA levels in cisplatin-treated rats. In conclusion, the present study shows that the TQ synergizes with its nephroprotective effect against cisplatin-induced acute kidney injury in rats.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 03/2012; 50(5):1675-9. · 2.99 Impact Factor
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ABSTRACT: Cisplatin-induced nephrotoxicity is related to an increase in oxidative stress in the kidney. Lycopene, a carotenoid found in tomatoes, is a potent dietary antioxidant. In the present study, we investigated the effect of the tomato lycopene complex against cisplatin-induced lipid peroxidation and nephrotoxicity in rats. Male Wistar rats (n = 28, 8 wk old, between 200-215 g) were divided into 4 groups: (a) control, (b) tomato lycopene complex (6 mg/kg, daily; consisting of 6% lycopene, 1.5% tocopherols, 1% phytoene and phytofluene, and 0.2% β-carotene), (c) cisplatin (7 mg/kg i.p., single dose), and (d) cisplatin + tomato lycopene complex. Cisplatin administration increased serum urea-N (171 vs. 37 mg/dl) and creatinine (1.80 vs. 0.42 mg/dl) and decreased body weight in comparison with the control rats (P < 0.001). Serum creatinine and urea-N levels were lower in rats treated with tomato lycopene complex + cisplatin compared with rats treated with cisplatin alone (P < 0.001). The renal tissue from the cisplatin-treated rats had greater malondialdehyde (MDA; 172 vs. 93 nmol/g) and 8-isoprostane levels (1810 vs. 610 pg/g) than that from the control rats (P < 0.001). Tomato lycopene complex prevented the rise of MDA and 8-isoprostane (P < 0.001). No measurable lycopene could be detected in the serum of the control and cisplatin-treated rats, whereas lycopene was observed in the serum of rats supplemented with tomato lycopene complex. Renal Bax protein expression was significantly higher in the cisplatin-treated rats than in the control rats, and tomato lycopene complex treatment significantly reduced Bax expression (P < 0.001). The expression of Bcl-2 was higher in tomato lycopene complex/cisplatin-treated rats than in the cisplatin-injected rats (P < 0.05). The expression of renal HSP60 and HSP70 was significantly lower in tomato lycopene complex + cisplatin-treated rats than in rats treated with cisplatin alone (P < 0.001). These results suggest that tomato lycopene complex has protective effects against cisplatin-induced nephrotoxicity and lipid peroxidation in rats.
Nutrition and Cancer 03/2011; 63(3):427-34. · 2.78 Impact Factor
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ABSTRACT: Cisplatin-induced nephrotoxicity is related to an increase in lipid peroxidation, oxygen-free radicals, and inflammation in kidney. Zinc is an antioxidant and has anti-inflammatory action. To date, the protective role of zinc picolinate on cisplatin-induced renal injury has not been investigated. The purpose of the present study was to examine the effect of zinc picolinate on cisplatin-induced renal injury.
Male Wistar rats (n = 28, 8-week-old, weighing 200 to 220 g) were divided into four groups consisting of 7 rats each: control, zinc picolinate (6 mg Zn kg(-1) BW i.p.), cisplatin (7 mg kg(-1)BW i.p., single dose) and cisplatin plus zinc picolinate.
A single dose of cisplatin resulted in an increase in malondialdehyde, 8-isoprostane, and tumor necrosis factor-α levels of kidney and significantly deranged renal function (urea-N and creatinine; P < .0001). Zinc picolinate treatment significantly reduced urea-N, creatinine, malondialdehyde, 8-isoprostane, and tumor necrosis factor-α -α levels. Concentration of zinc in kidney was increased significantly after zinc picolinate supplementation; however, Fe and Cu levels did not change. Expression of Bax in kidney increased with cisplatin administration, and this could be prevented by zinc picolinate treatment (P < .001). However, bcl-2 expression did not change by zinc or cisplatin treatment (P > .05). The expression of heat shock proteins 60 and 70 in kidney was increased after cisplatin treatment compared with the levels in the control (P < .01), and this increase could be prevented by the zinc picolinate treatment (P < .05).
These results suggest that zinc picolinate may be a potential preventive agent in cisplatin-induced renal injury through decreasing oxidative stress and inflammation.
Journal of Renal Nutrition 11/2010; 20(6):398-407. · 1.57 Impact Factor
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ABSTRACT: Cisplatin-induced nephrotoxicity is associated with increased oxidative stress and inflammatory cytokines in the kidney. Epigallocatechin-3-gallate (EGCG) has anti-oxidant, anti-inflammatory, and anti-tumorigenic properties. In this study, we investigated the effects of EGCG on cisplatin-induced nephrotoxicity and potential mechanisms by which it enhances antioxidant activities and resolves inflammation after EGCG treatment during cisplatin-induced nephrotoxicity.
Twenty-eight rats were divided into four groups as control (group 1; no treatment; n=7), EGCG (group 2; n=7), cisplatin (group 3; n=7) or cisplatin and EGCG (group 4; n=7). After 2 days of EGCG treatment at a dose of l00 mg/kg BW, rats were treated with a single i.p. injection of cisplatin (7 mg/kg BW). On day 12 (10days after the cisplatin treatment), all rats were sacrificed by cervical dislocation. The level of protein was examined by Western blotting.
Cisplatin caused a significant decrease in the expression nuclear levels of NF-E2-related factor-2 (Nrf2), heme oxygenase-1(HO-1), and an increase in the levels of nuclear factor-kappa B (NF-kappaB p65) and 4-hydroxynonenal (HNE) an oxidative stress marker. EGCG supplementation significantly improved the changes associated with cisplatin nephrotoxicity by increasing levels of Nrf-2 and HO-1, and decreasing levels of NF-kappaB and HNE. Renal activities of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase) and glutathione were significantly lower in cisplatin-treated rats compared with control rats, and EGCG treatment significantly increased the activities of antioxidant enzymes and glutathione (P<0.001).
The results suggest that Nrf2/HO-1 signaling pathway may be the primary target for prevention of cisplatin-induced nephrotoxicity by EGCG, and that reduces it inflammation by inhibiting NF-kappaB.
Life sciences 08/2010; 87(7-8):240-5. · 2.56 Impact Factor
