Royal jelly arranges apoptotic and oxidative stress pathways and reduces damage to liver tissues of rats by down-regulation of Bcl-2, GSK3 and NF-κB and up-regulation of caspase and Nrf-2 protein signalling pathways.

IntroductionRoyal jelly (RJ) from the honey bee, Apis mellifera, is a traditional product that is widely used as a food supplement to support the medical treatment of various diseases.Material and methodsOur study continued for 8 weeks. 42 Wistar albino (8 weeks old) male rats were used in the study. The study included 6 groups; Group 1: Control group (fed with standard diet), Group 2: RJ (100 mg/kg, bw), Group 3: F-50 (50 mg/kg, bw), group 4: F-100 (100 mg/kg, bw) group 5: F-50 (50 mg/kg, bw) + RJ (100 mg/kg, bw) Group 6: F-100 (100 mg/kg, bw) + RJ (100 mg/kg, bw). Malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) activities in liver tissue were determined by spectrophotometer. Liver tissue samples were examined histopathologically and various protein levels were determined by Western blotting technique.ResultsRJ caused a significant decrease in MDA level, Bcl-2, GSK3 and NF-κB protein expression levels, whereas induced a significant increase in GSH level, CAT activities and Bax, BDNF, caspase-6, caspase-3, Nrf-2 protein expression levels.ConclusionOur findings suggest RJ to be used as a hepatoprotective agent in the clinic to modulate the toxic effects of fluoride and other chemicals in the future.

Protective effect of royal jelly on fluoride-induced nephrotoxicity in rats via the some protein biomarkers signalling pathways: a new approach for kidney damage.

INTRODUCTION: Protective effect of royal jelly (RJ) on fluoride-induced nephrotoxicity was investigated in this study. METHODS: 42 healthy male Wistar rats (n = 42, 8 weeks of age) were divided equally into 6 groups with 7 rats in each; (1) Group-1: Controls fed with standard diet; (2) Group-2: RJ [100 mg/kg] bw (body weight), by oral gavage; (3) Group-3: Fluoride [50 mg/kg] bw, in drinking water; (4) Group-4: Fluoride [100 mg/kg] bw, in drinking water; (5) Group-5: RJ [100 mg/kg] bw, by oral gavage + Fluoride [50 mg/kg] bw, in drinking water; (6) Group-6: RJ [100 mg/kg] bw, by oral gavage + Fluoride [100 mg/kg] bw, in drinking water. After 8 weeks, all rats were decapitated and their kidney tissues were removed for further analysis. The protein expression levels of caspase-3, caspase-6, caspase-9, Bcl-2, Bax, VEGF, GSK-3, BDNF, COX-2 and TNF-α proteins in kidney tissue were analysed by western blotting technique. RESULTS: RJ increased Bcl-2, COX-2, GSK-3, TNF-α and VEGF protein levels and a decreased caspase-3, caspase -6, caspase-9, Bax and BDNF protein levels in fluoride-treated rats. CONCLUSION: RJ application may have a promising therapeutical potential in the treatment of many diseases in the future by reducing kidney damage.

Ellagic acid inhibits proinflammatory intermediary manufacture by suppressing NF-κB/Akt, VEGF and activating Nrf-2/Caspase-3 signaling pathways in rat testicular damage: a new way for testicular damage cure and in silico approach.

Ellagic acid (EA) has protective effect on testicular damage and this natural compound decreases oxidative damage. The present study aims to examine the preventive effect of ellagic acid (EA) against carbon tetrachloride (CCl4)-induced testicular tissue damage in rats. In testicular tissue, tumor necrosis factor-α (TNF-α), Nuclear factor erythroid-2 related factor 2 (Nrf-2), B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor (VEGF), Nuclear factor-kappa B (NF-κB), cysteine aspartic proteases (caspase-3) and protein kinase B (Akt) synthesis levels were analyzed by western blot method, reactive oxygen species (ROS) was measured by malondialdehyde (MDA) levels, Glutathione (GSH) level and catalase (CAT) by spectrophotometer. As a result, in comparison with the CCl4 group, caspase-3 and Nrf-2 protein synthesis levels increased in EA + CCl4 group, however, VEGF, Bcl-2, NF-κB, TNF-α and Akt protein synthesis levels decreased, EA application raised GSH levels and CAT activity, reduced MDA levels. In this study, in silico tools were applied to confirm the activity of EA against the cancer with macromolecules such as the above mentioned transcription factors. EA, turned out to show significant activity similarly to some cocrystal ligands, particularly against cancer. These results points out that EA can be used as a testicular damage cure drug in future.

The impact of ellagic acid on some apoptotic gene expressions: a new perspective for the regulation of pancreatic Nrf-2/NF-κB and Akt/VEGF signaling in CCl4-induced pancreas damage in rats.

OBJECTIVE: The aim of this study was to evaluate the potential effect of ellagic acid (EA) in the treatment of pancreatic injury. EA has been found to have strong anti-inflammatory, antioxidative, and anticancer properties. The effects of EA on pancreati˜c star cell (PSC) activation and cell functions have been evaluated and it has been shown that it inhibits the activation of basic cell functions and PSCs and. it has antidiabetic activity through its effect on ß-pancreas cells. MATERIALS AND METHODS: In this work, 36 Wistar albino rats (n = 36, 8 weeks old) were used. Rats were divided to 4 groups and 9 rats were each group. Groups: Group 1: control group; Group 2: EA group; Group 3: carbon tetrachloride (CCl4) group; Group 4: EA + CCl4 group. Animals were decapitated after 8 weeks and their pancreas tissue samples were taken and researched. In pancreas tissue, NF-κB, TNF-α, Nrf-2, VEGF, Bcl-2, caspase-3, and Akt proteins expression ratios were analyzed by western blotting method, CAT activity and GSH levels were determined by spectrophotometer and ROS production was detected by MDA. RESULTS: In our results, the Nrf-2 and caspase-3 protein expressions, catalase activities and GSH levels increased, TNF-α, NF-κB, Bcl-2, VEGF, and Akt protein expressions and MDA levels reduced in EA + CCl4 group comparable to the CCl4 group. CONCLUSIONS: These findings reveal that EA decreases pancreas tissue injury in rats and that EA may also be used as a drug against pancreas tissue injury in the future.

Royal jelly abrogates flouride-induced oxidative damage in rat heart tissue by activating of the nrf-2/NF-κB and bcl-2/bax pathway.

Royal jelly is known to strengthen memory, provide antioxidative, antidiabetic, antitumor, anticancer, antibacterial, antiinflammatory, antihypertensive. In this study, 42 rats (n = 42) were used, and these rats were divided into 6 groups of 7 rats each. Groups: (i) Control Group: Group fed with standard diet; (ii) Royal Jelly (RJ) Group: RJ (100 mg/kg bw, gavage); (iii) F50 Group: Fluoride (50 mg/kg bw, drinking water); (iv) F100 Group: F (100 mg/kg bw, drinking water); (v) F50 + RJ Group: F (50 mg/kg bw, drinking water) + RJ (100 mg/kg bw, gavage); (vi) F100 + RJ Group: F (100 mg/kg bw, drinking water) + RJ (100 mg/kg bw, gavage). The rats were decapitated after 8 weeks, and their heart tissues were taken and examined. Lipid peroxidation by MDA (malondialdehyde) analyzes, GSH (glutathione) level and catalase activity were determined by spectrophotometer. Protein expression levels of caspase-3, caspase-6, caspase-9, Bcl-2, Bax, BDNF, Gsk-3, Nrf-2 and NF-κB proteins in heart tissue were determined by western blotting technique and hearth tissue evaluated by histopathologically. As a result, MDA levels, Bcl-2, Gsk-3 and NF-κB protein expression levels were reduced, whereas GSH levels, caspase-3, caspase-9, caspase-6, Bax, BDNF and Nrf-2 protein levels were increased in the F50 + RJ and F100 + RJ groups compared to the F50 and F100 groups. According to the results of this study, it has been concluded that Royal jelly has the potential to be developed in to a drug for treatment of heart diseases in addition to providing protection against heart damage.

The effect of ellagic acid on caspase-3/bcl-2/Nrf-2/NF-kB/TNF-α /COX-2 gene expression product apoptosis pathway: a new approach for muscle damage therapy.

The goal of this study was to determine the protective role of ellagic acid (EA) against CCl4-induced muscle injury in rats. In this study, 36 Wistar albino rats (n = 36, 8 weeks old) were used. The rats were divided into 4 groups and 9 rats were included each group. Groups: (i) control Group: standard diet; (ii) EA Group: standard diet + EA group; (iii) CCl4 group: standard diet + CCl4 group; (iv) EA + CCl4 group: standard diet + EA + CCl4. The animals were decapitated after 8 weeks, and their muscle tissues were received and investigated. In the muscle tissue, TNF-α, COX-2, Nrf-2, NF-kB, caspase-3 and bcl-2 expression levels were analyzed by the western blotting technique, lipid peroxidation was detected by MDA (malondialdehyde), and catalase and GSH levels were determined by a spectrophotometer. In our findings, in comparison to the CCl4 group, in the EA + CCl4 group, the Nrf-2 and caspase-3 protein expression levels, GSH and catalase activities increased, while the NF-kB, bcl-2, TNF-α and COX-2 protein expression levels and MDA levels decreased. These results suggest that EA reduces muscle tissue damage rate in rats and that EA may also be used as a potential drug to protect against muscle tissue damage in the future.

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.

Serum sirtuin 1 protein as a potential biomarker for type 2 diabetes: Increased expression of sirtuin 1 and the correlation with microRNAs.

BACKGROUND: Type 2 diabetes (T2DM) is characterized by hyperglycemia and insulin deficiency. Sirtuin 1 (SIRT1), serving as a deacetylase, is critical in the regulation of glucose and lipid metabolism. Recently, a number of studies have been conducted to investigate the role of SIRT1 in the pathogenesis of T2DM. However, there are no sufficient data about the relationship between SIRT1 and T2DM. The aim of this study was to analyze the expressions of microRNAs (miRNAs) (miR-34a, miR-9, miR-132, and miR-181a) involved in SIRT1 regulation and SIRT1 protein in the serum of T2DM patients and controls. MATERIALS AND METHODS: miRNA expressions were determined by real-time polymerase chain reaction, and enzyme-linked immunosorbent assay was used to measure the SIRT1 protein levels in 25 T2DM patients and 25 controls. RESULTS: Fasting blood glucose and glycated hemoglobin levels were significantly higher in patients when compared with controls (P < 0.001). There was no difference for miRNA expressions between the groups (P > 0.05). SIRT1 protein level was significantly increased in patients as compared to controls (P = 0.044). Moreover, SIRT1 was negatively correlated with miR-181a (r = -0.558, P = 0.005) and miR-132 (r = -0.435, P = 0.034) in patients. CONCLUSION: Obtained results indicate that serum SIRT1 may be a potentially new biomarker for T2DM and also miR-181a and miR-132 may be involved in the development of T2DM by targeting SIRT1. This is the first study reporting on the effects of SIRT1 and related miRNAs in Turkish T2DM patients.

The role of vitamin D receptor gene polymorphisms in Turkish infants with urolithiasis.

Polymorphisms in the vitamin D receptor (VDR) gene have recently been reported to be associated with urinary calculi in pediatric and adult cases, but no studies have looked at the youngest period of life. The purpose of this study was to investigate the role of VDR gene polymorphisms in infantile urolithiasis in a Turkish population. We compared a study group of 104 infants (55 girls and 49 boys, mean age 6.94 ± 3.81 months) with a control group of 96 infants (51 girls and 45 boys, mean age 7.51 ± 3.23) to evaluate their demographics and metabolic risk factors. PCR-based restriction analysis of the polymorphisms on the VDR gene (BsmI and TaqI) showed statistically significant differences between study and control groups (p = 0.001 and 0.043, respectively). In addition, the prevalence of the BsmI genotype was significantly different between the hypercalciuric and normocalciuric stone formers (p = 0.007). Allelic frequencies were similar between the urolithiasis and control groups (p > 0.05). The B allele of BsmI and the A allele of ApaI were more prevalent in the hypercalciuric stone formers than in the normocalciuric stone formers (p = 0.018 vs.0.036, respectively). These results suggest that the BsmI and TaqI VDR genotypes could be candidate genes leading to infantile urolithiasis.

A novel non-surgical, minimally invasive technique for parathyroid autotransplantation: a case report.

We present a case report of intramuscular autotransplantation of the parathyroid cell suspension acquired after total parathyroidectomy. A 15-yr-old female patient who had been undergoing hemodialysis due to chronic renal failure for eight yr was diagnosed with secondary hyperthyroidism and subsequently underwent total parathyroidectomy. The parathyroid cells were acquired from the resected tissues, processed through isolation and cultivation phases, and counted using a cell counter. A total of two million cells were injected into the left deltoid muscle using a 22-gauge needle. After surgery, five and 10 million cells were injected in the fifth and 12 week, respectively. The desired serum levels of parathyroid hormones and calcium were not achieved after the first two transplantations. In addition, there was no regression in the patient's symptoms. However, at four wk after the third transplantation, serum parathyroid hormone level did not decrease to <3 pg/mL, the patient was asymptomatic, and the oral treatment was stopped. Our findings indicate that this new technique is applicable because it is minimally invasive, and it can be easily repeated.

SIRT1 gene variants are related to risk of childhood obesity.

UNLABELLED: Obesity is a multifactorial disorder resulting from the interaction between genetic, psychological, physical, environmental, and socioeconomic factors. SIRT1 gene has important effects on the regulation of adiponectin, caloric restriction, insulin sensitivity, coronary atherosclerosis, and cardiovascular diseases. The aim of this study was to investigate the association between childhood obesity and SIRT1 gene polymorphisms regarding rs7895833 A > G in the promoter region, rs7069102 C > G in intron 4, and rs2273773 C > T in exon 5 using PCR-CTPP method in 120 obese and 120 normal weight children. In this study, BMI, systolic and diastolic blood pressure, LDL cholesterol, triglyceride, and insulin levels were significantly higher and HDL-cholesterol levels were significantly lower in obese children compared to normal weight children. For rs7895833 A > G, the rate of having AG genotype and G allele was significantly higher in obese children compared to non-obese group (p < 0.001). The risk for obesity was increased by 1.9 times in G allele carriers; therefore, A allele may be protective against obesity. Both study groups had CT heterozygote genotype for rs2273773 C > T. There was no significant difference for rs7069102 C > G gene polymorphism between groups. CONCLUSION: This is the first study reporting an association between SIRT1 gene polymorphisms and obesity in children.

Efficacy of statins on sirtuin 1 and endothelial nitric oxide synthase expression: the role of sirtuin 1 gene variants in human coronary atherosclerosis.

Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and are used to reduce the risk of coronary artery disease (CAD) due to their pleiotropic effects. Recently, greater focus has been placed on the role of sirtuin 1 (SIRT1) in cardiovascular disease research. However, insufficient data exist on the relationships between statins, SIRT1 protein levels, and SIRT1 gene variants. In the present study, we investigated the effects of statins, atorvastatin and rosuvastatin, in CAD patients by analysing the associations between SIRT1 gene variants, rs7069102C>G and rs2273773C>T, and SIRT1/endothelial nitric oxide (eNOS) expression, as well as total antioxidant and oxidant status, and the oxidative stress index. SIRT1 expression was significantly higher, and eNOS expression was significantly lower in CAD patients when compared with controls. Statin treatment reduced SIRT1 expression and increased eNOS expression, similar to the levels found in the control population, independent from the studied SIRT1 gene variants. Oxidative stress parameters were significantly increased in CAD patients, and were decreased by statin treatment, demonstrating the antioxidative effects of statins on atherosclerosis. These results indicate that statin treatment could produce its protective effect on cardiovascular disease through the inhibition of SIRT1 expression. This is the first study reporting on the effect of statins, specifically atorvastatin and rosuvastatin, on SIRT1 expression in CAD patients.

GAS6 intron 8 c.834 + 7G > A gene polymorphism in diabetic nephropathy.

UNLABELLED: BACKGROUND - AIM: In animal experiments, growth arrest-specific 6 (Gas6) protein plays a key role in the development of mesangial cell and glomerular hypertrophy in the early phase of diabetic nephropathy, and diabetic nephropathy is prevented by warfarin-induced inhibition of GAS6 protein. It was shown that GAS6 intron 8 c.834 + 7G > A polymorphism is protective against type 2 diabetes mellitus, and AA genotype is associated with higher blood levels of GAS6 protein. Our aim is to investigate whether this polymorphism is a risk factor for diabetic nephropathy in type 2 diabetes mellitus. METHOD: Eighty-seven patients with diabetic nephropathy were compared with 66 non-diabetic controls in terms of GAS6 intron 8 c.834 + 7G > A polymorphism. Patients with history of stroke, ischemic heart disease were excluded. Each patient was examined by the ophthalmologist to determine diabetic retinopathy. RESULTS: Frequency of GG, GA and AA genotypes are similar in diabetic nephropathy and control groups according to GAS6 intron 8 c.834 + 7G > A polymorphism (p = .837). Rate of diabetic retinopathy was 54.02%. In the subgroup analysis, GA genotype was significantly more frequent than GG genotype in patients with diabetic retinopathy when compared to without diabetic retinopathy (p = .010). CONCLUSION: In our study, GAS6 intron 8 c.834 + 7G > A polymorphism was not associated with diabetic nephropathy in type 2 diabetes mellitus. However, heterozygous state of this polymorphism may be a risk factor for diabetic retinopathy in patients with diabetic nephropathy.

Melatonin attenuates phenytoin sodium-induced DNA damage.

Phenytoin sodium (PHT Na(+)) is a potent antiepileptic drug against epileptic seizures and is used as a prophylactic treatment in traumatic brain injury. PHT Na(+) leads to the formation of reactive oxygen species (ROS), and DNA is a crucial molecular target of ROS-initiated toxicity. Melatonin and its metabolites possess free-radical-scavenging activity. We therefore designed this study to investigate the potential protective effect of melatonin against PHT Na(+)-induced DNA damage by using the comet assay in a rat model in vivo. Thirty-three 3-month-old male Wistar rats were divided into five groups of control treated with isotonic sodium chloride (a single injection of isotonic sodium chloride and 100 µL in drinking water for 10 days), ethanol treated (in drinking water for 10 days containing 100 µL of ethanol in each 300-mL drinking bottle), melatonin treated (4 mg/kg body weight [b.w.] intraperitoneally [i.p.] at the start, in drinking water for 10 days), PHT Na(+) treated (a single i.p. injection of 50 mg/kg) and PHT Na(+) (50 mg/kg b.w., single i.p.) and melatonin (4 mg/kg b.w. i.p. at the start and 4 mg/kg in drinking water for 10 days) cotreated. To determine the protective effects of melatonin, the comet assay was performed using lymphocytes isolated in different time intervals (0, 15, 30, 45 and 60 minutes) from each group of animals. On days 1, 3, 7 and 10, blood samples were taken and the comet assay technique was performed. Our present data suggest that melatonin reversed PHT Na(+)-induced DNA damage.

Serum paraoxonase 1 activity and oxidative stress in pediatric patients with pulmonary tuberculosis.

OBJECTIVES: The aim of this study was to determine the oxidative stress and paraoxonase 1 (PON1) levels in children with pulmonary tuberculosis (TB) compared to healthy controls, and to examine the association of demographical with oxidative stress. SUBJECTS AND METHODS: Forty children diagnosed with pulmonary TB and 40 age- and gender-matched healthy controls were enrolled in the study. Serum total antioxidant status (TAS), total oxidant status (TOS) and PON1 levels were measured. The oxidative stress index (OSI) was calculated to indicate the degree of oxidative stress. RESULTS: The TAS levels were lower (1.73 ± 0.5 vs. 2.54 ± 1.2 µmol Trolox Eq/l) while TOS levels were significantly higher (26.9 ± 14.4 vs. 13.4 ± 7.7 µmol H2O2 Eq/l) in the TB group than in the controls (p < 0.001). The OSI was significantly higher in the TB group than in the controls (21.2 ± 5.1 vs. 6.5 ± 4.9 units, p = 0.006). Serum PON1 levels were significantly lower in the TB group than in the controls (14.2 ± 13.2 vs. 28.4 ± 17.3 U/l, p < 0.001). The lower PON1 levels correlated with TAS and OSI levels but not with anthropometric parameters (r = 0.264, p = 0.018 and r = -0.255, p = 0.023, respectively). CONCLUSION: The TOS and OSI levels were higher and the TAS and PON1 levels were lower in pediatric patients with pulmonary TB when compared to healthy controls. This indicates greater oxidative stress in the patients.

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.

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.

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.

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.

Activation of Nrf-2 Transcription Factor and Caspase Pathway with Royal Jelly Reduces Fluoride Induced Testicular Damage and Infertility in Rats.

This study was carried out to investigate the protective properties of royal jelly on the testicular tissue of rats with testicular damage by giving fluoride. Sperm motility, epididymal sperm density and abnormal sperm ratios were examined and visualized with a light microscope. Expression levels of Caspase-3, Bcl-2, Nrf-2, NF-κB, COX-2, TNF-α and IL1-α proteins in testis tissue were determined by western blot technique. As a result of the study, MDA level, expression level of Bcl-2, NFÒ¡B, COX-2, TNF-α and IL1-α proteins, abnormal sperm rates were found higher in Fluoride-50 and Fluoride100 groups compared to other groups. In addition GSH, Catalase enzyme levels, expression levels of Caspase-3 and Nrf-2 proteins were found to be higher in Fluoride + Royal Jelly groups compared to Fluoride-50 and Fluoride-100 groups. In addition, lower degeneration of testicular tissue was found in the histological evaluation in the Fluoride + Royal Jelly groups compared to the other groups. When the data are evaluated royal jelly provides effective protection against testicular damage. From this point of view, we hope that similar results will be obtained when royal jelly is tested on humans.