The Effect of Thymoquinone on the TNF-α/OTULIN/NF-κB Axis Against Cisplatin-Induced Testicular Tissue Damage.

One of the adverse effects of the antineoplastic drug cisplatin (CS) is damage to testicular tissue. This study aimed to examine the potential therapeutic effect of thymoquinone (TQ), a strong antioxidant, against testicular damage caused by CS. In the experiment, 28 rats were used, and the rats were randomly divided into four groups: control (n = 7), CS (n = 7), CS + TQ (n = 7), and TQ (n = 7). The experiment was called off after all treatments were finished on day 15. Blood serum and testicular tissues were utilized for biochemical, histological, immunohistochemical, mRNA expression, and gene protein investigations. The testosterone level decreased and oxidative stress, histopathological damage, dysregulation in mitochondrial dynamics, inflammation and apoptotic cells increased in testicular tissue due to CS administration. TQ supplementation showed anti-inflammatory, antioxidant, and anti-apoptotic effects in response to CS-induced testicular damage. In addition, TQ contributed to the reduction of CS-induced toxic effects by regulating the TNF-α/OTULIN/NF-κB pathway. TQ supplementation may be a potential therapeutic strategy against CS-induced testicular damage by regulating the TNF-α/OTULIN/NF-κB axis, inhibiting inflammation, oxidative stress, and apoptosis.

Fullerene C60 protects against 7,12-dimethylbenz [a] anthracene (DMBA) induced-pancreatic damage via NF-κB and Nrf-2/HO-1 axis in rats.

The objective of this investigation was to investigate the protective effects of fullerene C60 nanoparticle against pancreatic damage experimentally induced by 7,12-dimethylbenz [a] anthracene (DMBA) in female rats. Fullerene C60 nanoparticle was administered to rats 5 times a week by oral gavage (o.g) at 1.7 mg/kg bw 7 days after DMBA administration. 60 Wistar albino female rats divided to four groups; Groups: (1) Control group: Fed with standard diet; (2) Fullerene C60 group: Fullerene C60 (1.7 mg/kg bw); (3) DMBA group: DMBA (45 mg/kg bw); (4) Fullerene C60 + DMBA group: Fullerene C60 (1.7 mg/kg bw) and DMBA (45 mg/kg bw). Lipid peroxidation malondialdehyde (MDA), catalase activity (CAT) and glutathione (GSH) levels in pancreatic tissue were determined by spectrophotometer. Protein expression levels of p53, HO-1, p38-α (MAPK), Nrf-2, NF-κB and COX-2 in pancreatic tissue were determined by western blotting technique. In our findings, compared to the group given DMBA, MDA levels and p38-α, NF-κB and COX-2 levels decreased, CAT activity, GSH level, total protein density and p53, HO-1, Nrf-2 levels in the groups given fullerene C60 nanoparticle an increase in expression levels was observed. Our results showed that fullerene C60 nanoparticle may be more beneficial in preventing pancreatic damage.

Fullerene C60 reduces acute lung injury by suppressing oxidative stress-mediated DMBA-induced apoptosis and autophagy by regulation of cytochrome-C/caspase-3/beclin-1/IL-1α/HO-1/p53 signaling pathways in rats.

The objective of this study was to evaluate the effect of fullerene C60 nanoparticles against 7,12-dimethylbenz[a]anthracene (DMBA)-induced lung tissue damage in rats. 60 Wistar albino (8 weeks old) female rats were assigned into four groups: Control Group (C), Fullerene C60, DMBA, and Fullerene C60+DMBA. The rats in the DMBA and Fullerene C60+DMBA groups were administered DMBA (45 mg/kg bw, oral gavage). The rats in Fullerene C60, and Fullerene C60+DMBA groups were administered with Fullerene C60 (1.7 mg/kg bw, oral gavage). Expression levels of cytochrome-C, caspase-3, beclin-1, IL-1α, HO-1 and p53 proteins in lung tissue were determined by western blotting, lipid peroxidation malondialdehyde (MDA) analyzes, glutathione (GSH), glutathione peroxidase (GSH-Px), catalase activity (CAT) and total protein levels were determined by spectrophotometer. In addition, lung tissues were evaluated by histopathologically. Fullerene C60 reduced the increasing of MDA and IL-1α protein expression levels and attenuated histopathological changes in lung. Moreover, fullerene C60 enhanced the protein expression of cytochrome-C, caspase-3, beclin-1, HO-1, and p53, which were decreased in the DMBA group. Fullerene C60 has strong biological activity that it might be an effective approach for lung damage.

Royal jelly protects brain tissue against fluoride-induced damage by activating Bcl-2/NF-κB/caspase-3/caspase-6/Bax and Erk signaling pathways in rats.

This study is aimed at determining whether royal jelly (RJ) which has a powerful antioxidant property prevents fluoride-induced brain tissue damage and exploring whether Bcl-2/NF-κB/ and caspase-3/caspase-6/Bax/Erk pathways play a critical role in the neuroprotective effect of RJ. Wistar albino rats were chosen for the study, and they were randomly distributed into six groups: (i) control; (ii) royal jelly; (iii) fluoride-50; (iv) fluoride-100; (v) fluoride-50 + royal jelly; (vi) fluoride-100 + royal jelly. We established fluoride-induced brain tissue damage with 8-week-old male Wistar albino rats by administration of fluoride exposure (either 50 mg/kg or 100 mg/kg bw) through drinking water for 8 weeks. Then, the study duration is for 56 days where the rats were treated with or without RJ (100 mg/kg bw) through oral gavage. The effects of RJ on glutathione (GSH), catalase activity (CAT), and malondialdehyde (MDA) levels were determined via spectrophotometer. Western blot analysis was performed to investigate the effects of royal jelly on the protein expression levels of Bax, caspase-3, caspase-6, Bcl-2, NF-κB, COX-2, and Erk. It was also studied the effects of RJ on histopathological alterations in fluoride-induced damage to the rat brain. As a result, the Bcl-2, NF-κB, and COX-2 protein expression levels were increased in the fluoride-treated (50 and 100 mg/kg) groups but they were decreased significantly by RJ treatment in the brain tissue. Additionally, the protein expression of caspase-3, caspase-6, Bax, and Erk were decreased in fluoride-treated groups and they were significantly increased by RJ treatment compared to the un-treated rats. Our results suggested that RJ prevented fluoride-induced brain tissue damage through anti-antioxidant activities.

Nano-liquid chromatography with monolithic stationary phase based on naphthyl monomer for proteomics analysis.

Monolithic poly(2-vinylnaphthalene-co-divinylbenzene) columns were introduced, for the first time, and were evaluated as the separation media for nano-liquid chromatography (nano-LC). These columns were prepared by in-situ polymerization of 2-vinylnaphthalene (2-VNA) as the functional monomer and divinylbenzene (DVB) as the crosslinker in a fused silica capillary column of 50 µm i.d. Various porogenic solvents, including tetrahydrofuran (THF), dodecanol and toluene were used for morphology optimization. Final monolithic column (referred to as VNA column) was characterized by using scanning electron microscopy (SEM) and chromatographic analyses. Alkylbenzenes (ABs), and polyaromatic hydrocarbons (PAHs) were separated using the VNA column while the column offered excellent hydrophobic and π-π interactions under reversed-phase conditions. Theoretical plates number up to 41,200 plates/m in isocratic mode for ethylbenzene could be achieved. The potential of the final VNA column was demonstrated with a gradient elution in the  separation of six intact proteins, including ribonuclease A (RNase A), cytochrome C (Cyt C), lysozyme (Lys), ß-lactoglobulin (ß-lac), myoglobin (My) and α-chymotrypsinogen (α-chym) in nano LC system. The column was then applied to the peptide analysis of trypsin digested cytochrome C, allowing a high peak capacity up to 1440 and the further proteomics analysis of COS-7 cell line was attempted applying the final monolithic column in nano-LC UV system.

Fullerene C60 Attenuates Heart Tissue Inflammation by Modulating COX-2 and TNF-Alpha Signaling Pathways in DMBA Induced Breast Cancer in Rats.

The present study aimed to investigate the therapeutic effect of fullerene C60 nanoparticle against heart tissue damage caused by 7,12-dimethylbenz [a] anthracene (DMBA) in female rats. Female Wistar albino rats, 8 weeks old (n = 60) weighing around (150 ± 10 g) were used for the study. These rats were divided into 4 groups and each group included 15 rats. Groups: (i) Control Group: Fed with standard diet; (ii) C60 Group: C60 (1.7 mg/kg bw, oral gavage); (iii) DMBA Group: DMBA (45 mg/kg bw, oral gavage); (iv) C60 and DMBA Group: C60 (1.7 mg/kg bw, oral gavage) and DMBA (45 mg/kg bw, oral gavage) group. Malondialdehyde (MDA) analysis, catalase activity (CAT), and glutathione (GSH) in heart tissue were determined by spectrophotometer. In addition, heart tissue DNA damage was investigated. Caspase-3, p53, HO-1, COX-2, and TNF-α protein expression levels in heart tissue were determined by western blotting. As a result, Caspase-3, p53, HO-1 protein expression, GSH levels and CAT activity increased, COX-2, TNF-α protein expression, and MDA levels were significantly decreased in the C60 + DMBA group compared to the DMBA group. Therefore, the fullerene C60 nanoparticle may be a promising and effective therapy for the treatment of heart diseases associated with inflammation.

In vivo, in vitro and in silico anticancer investigation of fullerene C60 on DMBA induced breast cancer in rats.

AIMS: The aim of the study was to determine the protective and therapeutic effect of fullerene C60 nanoparticle on DMBA-induced breast cancer in rats. MAIN METHODS: In vitro cell viability was determined by the WST-1 test. In vivo analysis was performed in female Wistar Albino rats. The expression of caspase-3, Bcl-2, Nrf-2, NF-κB, TNF-α, COX-2, p53, IL-6, IL-1α ve p38α (MAPK) proteins were assessed by western blotting. Furthermore, malondialdehyde (MDA), glutathione (GSH), catalase activity (CAT), total protein levels and DNA damage were investigated. In addition, tissues were evaluated by histopathologically. In in silico analysis, the binding affinities of the fullerene C60 nanoparticle to transcription factors such as caspase-3, Bcl-2, Nrf-2, NF-κB, TNF-α, COX-2, VEGF and Akt were demonstrated by molecular docking. KEY FINDINGS: Treatment of MCF-7 cells at various concentrations of fullerene C60 (0.1 to 100 mg/ml) inhibited cell viability in a dose dependent manner. Fullerene C60 treated rats exhibited considerable increase in the level of caspase-3 while decrease in the level of pro-survival protein Bcl-2. Bcl-2, NF-κB, TNF-α, COX-2, IL-6, IL-1α and p38α (MAPK) protein expression levels and malondialdehyde (MDA) levels were decreased in the C60 + DMBA groups compared to the DMBA group. It was observed that caspase-3, Nrf-2 and p53 protein expression levels, glutathione (GSH) level, catalase activities (CAT) and total protein levels increased significantly which was further confirmed through the resulting DNA fragmentation. SIGNIFICANCE: In silico assays, fullerene C60 has been observed to have similar affinity to some crystal ligands, especially against cancer.

Quercetin and Luteolin Improve the Anticancer Effects of 5-Fluorouracil in Human Colorectal Adenocarcinoma In Vitro Model: A Mechanistic Insight.

The aim of this study was to investigate the antitumor effects of quercetin and luteolin combined with 5-Fluorouracil (5-FU) in HT-29 human colorectal cancer cells. Cell viability induced by quercetin, luteolin and combination of these compounds with 5-FU were determined by MTT assay, also Cell death detection Elisa assay and fluorescence microscopy were performed to investigate apoptotic effects. Hu-VEGF Elisa assay was employed to determine the effects of treatments on angiogenesis. Western blot and qRT-PCR analysis were performed to investigate effects on p53, Bax, Bcl-2, p38 MAPK, mTOR, PTEN, and Akt proteins and genes. The results indicated that quercetin, luteolin and combinations of these compounds with 5-FU inhibited the growth of HT 29 cells. Compared to the control, apoptosis were triggered 8.1 and 10.1 fold in HT-29 cells, that treated with quercetin + 5-FU and luteolin + 5-FU, respectively. VEGF amount significantly decreased by combined treatments. qRT-PCR and western blot results demonstrated that quercetin, luteolin and the combinations of these flavonoids with 5-FU, modulate the apoptotic pathways in HT-29 cells. The increase in p53, Bax, p38 MAPK, and PTEN gene expression levels compared to the control group was 1.71, 1.42, 3.26, and 3.29-fold with 5-FU + L treatment, respectively, while this increase was 8.43, 1.65, 3.55, and 3.54-fold with 5-FU + Q treatment, respectively. In addition, when the anti-apoptotic Bcl-2, mTOR, and Akt gene expression levels were normalized as 1 in the control group, they were 0.28, 0.41, and 0.22 with 5-FU + L treatment, and 0.32, 0.46, and 0.39, respectively, with 5-FU + Q treatment. These findings suggested that quercetin and luteolin synergistically enhanced the anticancer effect of 5-FU in HT 29 cells and may therefore minimize the toxic effects of 5-FU in the clinical treatment of colorectal cancer.

Ellagic acid prevents kidney injury and oxidative damage via regulation of Nrf-2/NF-κB signaling in carbon tetrachloride induced rats.

Phytochemicals, bioactive food compounds, found in plants have been described as protective agents against renal injury. This work was planned to evaluate the effects of EA on anti-oxidative and anti-inflammation pathways in kidney damage induced with carbon tetrachloride. In this study, experimental animals (n = 36, 8 weeks old rats) were divided into 4 groups as follows: 1) Control group 2) EA group (10 mg/kg body weight) 3) CCl4 group (1.5 ml/kg, body weight) 4) EA + CCl4 group. The potentially protective effect of EA on kidney damage exposed by CCl4 in rats were evaluated. EA administration protects CCl4 induced kidney damage against oxidative stress through its antioxidant protection. Treatment of EA significantly reduced lipid peroxidation and improved glutathione and catalase enzyme activity. Recently studies showed that EA activated caspase-3 and nuclear transcription factor erythroid 2 related factor driven antioxidant signal pathway and protected the kidney against damage induced by oxidative stress. Furthermore, EA also markedly decreased the level of cyclooxygenase-2, the vascular endothelial growth factor and tumor necrosis factor-alpha and suppressed the protein synthesis of nuclear factor-kappa-B. This study reveals that EA has kidney protective effect against CCl4 induced oxidative damage and inflammation.

Pristine C60 Fullerene Nanoparticles Ameliorate Hyperglycemia-Induced Disturbances via Modulation of Apoptosis and Autophagy Flux.

Diabetes mellitus is a prevalent metabolic disorder associated with multiple complications including neuropathy, memory loss and cognitive decline. Despite a long history of studies on diabetic complications, there are no effective therapeutic strategies for neuroprotection in diabetes. Hyperglycemia-induced imbalance in programmed cell death could initiate a decline in neural tissue cells viability. Various nanomaterials can induce either cell death or cell survival dependent on the type and surface features. Pristine C60 fullerene is a nontoxic nanomaterial, which exhibits antioxidant and cytoprotective properties. However, the precise molecular mechanism with which the C60 nanoparticle exerts cytoprotective effect in diabetic subjects has not yet been fully addressed. Thus, this study aimed to determine whether C60 fullerene prevents oxidative stress impairment and to explore the effects of C60 fullerene on apoptosis and autophagy in diabetes mellitus to clarify its potential mechanisms. These effects have been examined for olive oil extracted C60 fullerene on the hippocampus of STZ diabetic rats. Up-regulation of Caspase-3, Beclin-1 and oxidative stress indexes and down-regulation of Bcl-2 were observed in the brain of STZ-diabetic rats. The exposure to C60 fullerene for a period of 12 weeks ameliorate redox imbalance, hyperglycemia-induced disturbances in apoptosis and autophagy flux via modulation of Caspase-3, Bcl-2, Beclin-1 and LC3I/II contents. Furthermore, C60 fullerene ameliorated the LC3I/II ratio and prevented extremely increased autophagy flux. Contrarily, pristine C60 fullerene had no modulatory effect on all studied apoptotic and autophagy markers in non-diabetic groups. Therefore, oil extracted C60 fullerene exhibits cytoprotective effect in hyperglycemia-stressed hippocampal cells. The presented results confirm that pristine C60 fullerene nanoparticles can protect hippocampal cells against hyperglycemic stress via anti-oxidant, anti-apoptotic effects and amelioration of autophagy flux. Moreover, C60 fullerene regulates a balance of autophagy via BCL-2/Beclin-1 reciprocal expression that could prevent functional disturbances in hippocampus.

The Effect of TIGAR Knockdown on Apoptotic and Epithelial-Mesenchymal Markers Expression in Doxorubicin-Resistant Non-Small Cell Lung Cancer A549 Cell Lines.

Resistance to chemotherapeutic drugs is a critical problem in cancer therapy, but the underlying mechanism has not been fully elucidated. TP53-induced glycolysis regulatory phosphatase (TIGAR), an important glycolysis and apoptosis regulator, plays a crucial role in cancer cell survival by protecting cells against oxidative stress-induced apoptosis. In the present study, we investigated whether TIGAR is involved in epithelial-mesenchymal transition (EMT) in doxorubicin (DOX)-resistant human non-small cell lung cancer (NSCLC), A549/DOX cells. We found that the expression of TIGAR was significantly higher in A549/DOX cells than in the parent A549 cell lines. siRNA-mediated TIGAR knockdown reduced migration, viability and colony survival of doxorubicin-resistant lung cancer cells. Also, TIGAR knockdown decreased pro-survival protein Bcl-2 and increased pro-apoptotic Bax and cleaved poly (ADP-ribose) polymerase (PARP). Moreover, TIGAR depletion significantly up-regulated both caspase-3 and caspase-9 expression. Furthermore, TIGAR depletion up-regulated the expression of E-cadherin and down-regulated the expression of vimentin. These results indicate that TIGAR knockdown may inhibit EMT in doxorubicin (DOX)-resistant human NSCLC and may represent a therapeutic target for a non-small lung cancer cells chemoresistance.

Deciphering of The Effect of Chemotherapeutic Agents on Human Glutathione S-Transferase Enzyme and MCF-7 Cell Line.

BACKGROUND: Cancer is the disease that causes the most death after cardiovascular diseases all over the world these days. Breast cancer is the most common type of cancer among women and ranks the second among cancer-related deaths after lung cancer. Chemotherapeutics act by killing cancer cells, preventing their spread and slowing their growth. Recent studies focus on the effects of chemotherapeutics on cancer cells and new chemotherapy approaches that targeting enzymes that catalyze important metabolic reactions in the cell. OBJECTIVE: The aim of this study was to investigate the effects of chemotherapeutic agents, Tamoxifen and 5-FU, on MCF-7 cell line and human erythrocyte GST, an important enzyme of intracellular antioxidant metabolism. METHODS: In this study, it was investigated that the effect of chemotherapeutic agents, Tamoxifen and 5-FU, on MCF-7 breast cancer cell line and performed ROS analyzes. In addition, it was purified glutathione S-transferase (GST), one of the important enzymes of intracellular antioxidant mechanism, from human erythrocytes by using ammonium sulfate precipitation and glutathione agarose affinity chromatography, and investigated in vitro effects of chemotherapeutic agents, 5 - FU and Tamoxifen, on the activity of this enzyme for the first time. RESULTS: it was determined that Tamoxifen and 5-FU inhibited cellular viability and 5-FU increased intracellular levels of ROS, whereas Tamoxifen reduced intracellular levels of ROS. In addition, human erythrocyte GST enzyme with 16.2 EU/mg specific activity was purified 265.97-fold with a yield of 35% using ammonium sulfate precipitation and glutathione agarose affinity chromatography. The purity of the enzyme was checked by the SDS-PAGE method. In vitro effects of chemotherapeutics, 5-FU and Tamoxifen, on GST activity purified from human erythrocytes were investigated. The results showed that 5-FU increased the activity of GST in the concentration range of 77 to 1155 µM and that Tamoxifen increased the activity of GST in the concentration range of 0.54 to 2.70 µM. CONCLUSION: In this study, the effects of tamoxifen and 5-FU chemotherapeutic agents on both MCF-7 cell line and human GST enzyme were examined together for the first time. Our study showed that chemotherapeutic agents (5-FU and Tamoxifen) inhibited cellular viability and Tamoxifen reduced intracellular levels of ROS whereas 5-FU increased intracellular levels of ROS. In addition, 5-FU and Tamoxifen were found to increase the activity of GST enzyme purified from the human erythrocyte.

The preventive effect of ellagic acid on brain damage in rats via regulating of Nrf-2, NF-kB and apoptotic pathway.

The aim of this study was to investigate the neuroprotective role of ellagic acid (EA) on CCl4 -induced brain injury in rats. In this study, the rats were divided into four groups. Groups: (1) Control group; (2) EA group; (3) CCl4 group; (4) EA + CCl4 group. In brain tissue, tumor necrosis factor-α (TNF-α), nuclear factor kappa b (NF-kB), cyclooxygenase-2 (COX-2), nuclear erythroid related factor 2 (Nrf-2), cysteine-aspartic acid protease (caspase-3), VEGF (vascular endothelial growth factor) and B-cell lymphoma-2 (bcl-2) protein expression levels were analyzed by western blotting. MDA (malondialdehyde), catalase enzyme activity (CAT) and glutathione (GSH) analysis were determined by spectrophotometer. In our findings, EA ameliorated Nrf-2 and caspase-3 protein expression levels, GSH and catalase activities, NF-kB, TNF-α, VEGF, Bcl-2, COX-2 protein expression levels and MDA levels in CCl4 intoxicated rats. These results suggest that EA demonstrated the neuroprotective effect on CCl4 -induced brain damage in rats. PRACTICAL APPLICATIONS: Ellagic acid has different biological activities, these are; antioxidant, anti-inflammatory, antidepressant, antifibrosis, anticancer, neuroprotective and hepatoprotective. For example it was reported that EA protects the cells against DNA injury induced by free radicals and it can prevent the traumatic brain injury. These results obtained from this study reveals that EA has a protective effect against rat brain damage and it may be used as an alternative drugs for the brain injury treatment in future.

Production and characterization of polyclonal antibodies to human recombinant domain B-free antihemophilic factor VIII.

Moroctocog alpha is a human B-domain deleted recombinant factor VIII (BDDrFVIII), which represents a new generation of pure antihemophilic products. We describe here an optimized procedure for polyclonal anti-FVIII-antibody production with the use of BDDrFVIII as an immunogen. The main immunochemical characteristics of the produced antibodies and their potential biomedical applications are also reported. Rabbits were immunized with BDDrFVIII as an emulsion with Freund's adjuvant or with antigen immobilized in polyacrylamide gel (PAAG). Antibody titers in immune sera were assayed by enzyme-linked immunosorbent assay (ELISA). IgG purification was performed by afine chromatography on protein A-sepharose. Immune sera and IgG were tested by immunoblotting with the use of human plasma of healthy donors and people with hemophilia A, platelet lysates, and commercial plasma-derived concentrates as sources of FVIII-related antigens. FVIII-producing human umbilical vein cells were processed for immunocytochemical staining with the use of purified anti-FVIII-antibodies. Immunization of rabbits with PAAG-trapped antigen induced more potent immune response compared to the standard immunization procedure with Freund's adjuvant. The lowest working amount of immune IgG, measured by ELISA, was ~50 ng. Immunoblotting demonstrated that anti-BDDrFVIII antibodies effectively recognize the whole FVIII molecule (320 kDa), as well as different truncated polypeptides thereof, and are suitable for immunocytochemical analysis of FVIII-producing cells. An optimized procedure for the production of polyclonal antibodies against FVIII with the use of PAAG-immobilized BDDrFVIII (moroctocog alpha) was proposed and successfully validated. The produced antibodies are suitable for detecting and measuring FVIII-related antigens and may have various biomedical applications.

Taurine ameliorates neuropathy via regulating NF-κB and Nrf2/HO-1 signaling cascades in diabetic rats.

Diabetic neuropathy is one of common complications of diabetes mellitus. Hyperglycemia induced oxidative stress involves in the development of diabetic neuropathy, which could be reversed by supplementation of taurine, an endogenous antioxidant. This experiment was conducted to evaluate alterations in the expressions of transcription factors [nuclear factor kappa B (NF-κB), nuclear factor-E2-related factor-2 (Nrf2), and heme oxygenase 1 (HO-1)] and glucose transporters and glucose metabolism in the brain of diabetic rats. In a 2×2 factorially arranged groups, taurine (2%) or water was administered per orally to healthy and streptozotocin (STZ)-induced diabetic rats (n=10 per group) for 8 weeks. Diabetes was associated with weight loss, hyperglycemia, and oxidative stress as reflected by increased serum malondialdehyde (MDA) concentrations. Diabetic rat brains had increased the NF-κB expression and decreased the Nrf2, HO-1, GLUT1,3 expressions as compared to healthy rat brains. Supplemental taurine did not alter body weight and blood glucose concentration, but partially reduced serum MDA concentration in the diabetic rats. Taurine also partially alleviated neuroinflammation as reflected by suppressed the NF-κB expression and enhanced the Nrf2, HO-1, GLUT1,3 expressions in the diabetic rats. In conclusion, taurine reduces the severity of oxidative stress through activating antioxidative defense signaling pathway in diabetic rat brain.

Lycopene counteracts the hepatic response to 7,12-dimethylbenz[a]anthracene by altering the expression of Bax, Bcl-2, caspases, and oxidative stress biomarkers.

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.

Impact of chromium histidinate on high fat diet induced obesity in rats.

BACKGROUND: Chromium (Cr) is an essential trace element that has garnered interest for use as a weight loss aid, but its molecular mechanism in obesity is not clear. In this study, an attempt has been made to investigate the effects of chromium histidinate (CrHis) on glucose transporter-2 (GLUT-2), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB p65) and the oxidative stress marker 4-hydroxynonenal adducts (HNE) expressions in liver of rats fed high fat diet (HFD). METHODS: Male Wistar rats (n = 40, 8 wk-old) were divided into four groups. Group I was fed a standard diet (12% of calories as fat); Group II was fed a standard diet and supplemented with 110 µg CrHis/kg BW/d; Group III was fed a HFD (40% of calories as fat); Group IV was fed HFD and supplemented with 110 µg CrHis/kg BW/d. RESULTS: Rats fed HFD possessed greater serum insulin (40 vs.33 pmol/L) and glucose (158 vs. 143 mg/dL) concentration and less liver Cr (44 vs.82 µg/g) concentration than rats fed the control diet. However, rats supplemented with CrHis had greater liver Cr and serum insulin and lower glucose concentration in rats fed HFD (P < 0.05). The hepatic nuclear factor-kappa B (NF-κB p65) and HNE were increased in high fat group compared to control group, but reduced by the CrHis administration (P < 0.05). The levels of hepatic Nrf2 and HO-1 were increased by supplementation of CrHis (P < 0.05). CONCLUSION: These findings demonstrate that supplementation of CrHis is protective against obesity, at least in part, through Nrf2-mediated induction of HO-1 in rats fed high fat diet.

A tomato lycopene complex protects the kidney from cisplatin-induced injury via affecting oxidative stress as well as Bax, Bcl-2, and HSPs expression.

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% ß-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.