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.

Protective effects of rosmarinic acid against azoxymethane-induced colorectal cancer in rats.

Colorectal cancer (CRC) incidence is increasing gradually and has been become one of the most common cancers worldwide. Hence, it is important to discover cheap, naturally occurring compounds to be effective in suppressing the devastating effect of colon-related tumors. Rosmarinic acid (RA), one of the compounds of plant origin, possesses attractive features for use as an agent for cancer prevention and treatment. This study investigated the ability of RA to prevent azoxymethane (AOM)-induced rat colon carcinogenesis by evaluating the effect of RA on tumor formation and circulatory oxidant-antioxidant status. Moreover, plasma levels of adiponectin (APN) monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) were detected by enzyme linked immunosorbent assay. The animals were divided into three groups: Control, AOM, and AOM + RA. Rats were fed a modified pellet diet (15.8% peanut oil was added to the standard diet) during the experimental period. Colon cancer was formed by applying 15 mg/kg AOM intraperitoneal once a week for 4 weeks in both the CRC group and AOM + RA group. Besides AOM, AOM + RA group received 5 mg/kg body weight RA orally every day during the study. The results showed that adenocarcinoma rates formed 87.5% of the AOM group. With treatment of RA, a reduction in the incidence of adenocarcinoma was observed in the AOM + RA group. The plasma MCP-1, IL-6, and TO levels were significantly higher, APN and TAS levels were significantly lower in the AOM group with respect to controls. In addition, there was a significant increase in TAS levels in the RA treatment group compared to the AOM group. These findings suggested that RA may be beneficial in preventing AOM-induced colon carcinogenesis formation.

Evaluation of the Effects of Topical Application of Chlorhexidine, Ozone, and Metronidazole on Palatal Wound Healing: A Histopathological Study.

ABSTRACT: This study aimed to evaluate the effects of chlorhexidine, metronidazole, and ozone application on the healing of palatal wounds in diabetic rats. A defect in the form of a 4 mm-diameter wound was created on the palatal mucosa of 84 adult female Wistar albino rats, which were randomly divided into 4 groups: control, chlorhexidine, metronidazole, and ozone groups. The animals were euthanized after 3, 6, and 10 days, and wound closure was histologically assessed. On day 3, polymorphonuclear leukocytes were significantly higher in the control group than in the chlorhexidine and ozone groups ( P < 0.05). Fibrosis was higher in the ozone group than in the control and chlorhexidine groups ( P < 0.05). Vascular endothelial growth factor was higher in the metronidazole and ozone groups than in the control group ( P < 0.05). On day 6, the quantity of polymorphonuclear leukocytes was higher in the control, metronidazole, and chlorhexidine groups than in the ozone group ( P < 0.05). Vascular endothelial growth factor was higher in the ozone group than in the control, chlorhexidine, and metronidazole groups ( P < 0.05). On day 10, Vascular endothelial growth factor was higher in the control, chlorhexidine, and metronidazole groups than in the ozone group ( P < 0.05). The authors concluded that the use of chlorhexidine, ozone, and metronidazole pastes resulted in enhanced wound healing, as determined histologically.The authors suggest that ozone supplementation can be an alternative therapy to chlorhexidine in impaired wound healing in diabetes mellitus.

Evaluation of Effects of Systemic Zoledronic Acid Application on Bone Maturation in the Consolidation Period in Distraction Osteogenesis.

ABSTRACT: Distraction osteogenesis (DO) is a physiological process that generates new bone tissue formation, using progressively separated bone fragments. Recently, several techniques have been investigated to develop the maturation of the new bone tissue. Bisphosphonates was an effective material for the acceleration of bone formation in DO procedures. The purpose of this study was to evaluate the effects of the systemic zoledronic acid application at the beginning of the consolidation period on new bone genesis in a DO model of rat femurs. The rats were divided randomly into 3 groups, as follows: Control group (CNT group) (n = 10), zoledronic acid dosage-1 (n = 10), and dosage-2 (n = 10) groups (ZA-D-1 and ZA-D-2). No treatment was administered in controls, but DO was applied to the rat femurs. A single dose of 0.1 mg/kg and 0.2 mg/kg of zoledronic acid was administered systematically at the beginning of the consolidation period after the distraction in treatment groups, respectively. Histomorphometric analyses were performed on the original distracted bone area and the surrounding bone tissue. Osteoblasts, new bone formation, and fibrosis were scored. New bone formation in the ZA-D-1 and ZA-D-2 groups, when compared with the control group, was detected highly (P < 0.05). The numbers of osteoblasts in the ZA-D-1 and ZA-D-2 groups were higher when compared with the controls (P < 0.05). Fibrosis in the controls, when compared with the ZA-D-1 and ZA-D-2 groups, was found to be higher (P < 0.05). Zoledronic acid application is an effective method for bone maturation in consolidation period in DO.

Allyl isothiocyanate attenuates LED light-induced retinal damage in rats: exploration for the potential molecular mechanisms.

PURPOSE: Environmental light pollution due to artificial light may increase the rate and severity of retinal diseases, and plant-based nutritional interventions with antioxidant properties have the potential to reverse this phenomenon. We aimed to investigate the potential effects of allyl isothiocyanate (AITC) against white light-emitting diode (LED)-induced retinal degeneration (RD) in the rats. METHODS: Twenty-eight male rats were allocated as: (i) Control, (ii) LED, (iii) LED + AITC (10 mg/kg BW), (iv) LED + AITC (20 mg/kg BW). Rats were administered with AITC for 28 days, followed by two days of intense environmental LED light (750 Lux) exposure to the eyes. Animals were sacrificed immediately at the end of the study, then the blood and eyeballs were taken for the biochemical, western blotting, and histopathology examinations. RESULTS: AITC lowered the serum and retina malondialdehyde (MDA) levels while significantly (p < 0.05) improving the retinal antioxidant enzyme activities in a dose-dependent manner. AITC improved retinal and outer nuclear layer (ONL) thickness as compared to the LED group (p < 0.05). AITC increased the levels of Bax, caspase-3, HO-1, GAP43, and VEGF, while decreasing IL-1ß, IL-6, NF-κB, Bcl-2, GFAP, Grp78, activating ATF4 and ATF6 as compared to the LED group (p < 0.05). CONCLUSION: In conclusion, four weeks of AITC administration to the rats showed specific protective effects against two days of intense LED light-induced retinal damage; through antiinflammatory, antioxidant, anti-apoptotic, and modulating mitochondrial metabolic pathways.

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 inhibition of Src kinase suppresses the production of matrix metalloproteinases in from synovial fibroblasts and inhibits MAPK and STATs pathways

Background/aim: The purpose of this study was to investigate the antiarthritic potentials of the inhibition of Src kinase in vivo and in vitro settings. Materials and methods: Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund's adjuvant (collagen induced arthritis [CIA] model) in Wistar albino rats. One day after the onset of arthritis, dasatinib, a potent Src kinase inhibitor, (5 mg/kg/day) was given via oral gavage. Tissue Src, Fyn, MAPK and STAT mRNA expressions were determined by real-time polymerase chain reaction. On the other hand, fibroblast like synoviocytes (FLSs) were harvested patients with rheumatoid arthritis (RA) undergoing surgical knee joint replacement. FLSs were stimulated with cytokines and dasatinib was added in different concentrations. MMP ­1, ­3, and ­13 levels in FLSs culture were determined by ELISA. Results: The tissue mRNA expressions of Src, Fyn, MAPK and STATs were increased in the arthritis CIA group compared to the control group. Their mRNA expressions in the CIA + dasatinib group were decreased and similar in the control group. In in vitro setting, MMP ­1, ­3, and ­13 expressions from FLSs induced by IL-1ß and TNF-α were increased, while dasatinib suppressed their productions from FLSs. Conclusion: The present study shows that the inhibition of Src kinase has antiarthritic potentials in both in vivo and in vitro settings. Src kinase inhibition may be candidate to further research in human RA.

Comparison of the effect of topical bevacizumab and sorafenib in experimental corneal neovascularization.

PURPOSE: The purpose of this study was to compare the neovascularization inhibiting the effect of topical bevacizumab and sorafenib and to determine the effective dose of sorafenib. MATERIAL AND METHODS: Forty-two healthy Wistar albino rats were randomly divided into six groups. The right corneas of all rats except group 1 were cauterised with silver nitrate. Group 2 received DMSO, group 3 received topical bevacizumab (5 mg/dL, 3 times a day) and group 4, 5 and 6 received topical sorafenib (2.5 mg/dl, 5 mg/dL, 7.5 mg/dL, 2 times a day respectively), between days 1 and 7. Corneal photographs were taken on day 8 and the corneal neovascular area percentage was calculated. Following decapitation, the corneas were removed to determine the levels of VEGF ELISA and corneal immune staining. The Mann-Whitney U-test was used for statistical analysis. RESULTS: The neovascular corneal area percentage was statistically significantly lower in the treatment groups than group 2 (p < 0.05). The intensity of VEGF immune staining was also lower in groups 3, 5 and 6 from the group 2. Group 3, 5 and 6 were no significant differences compared to group 1. The VEGF ELISA levels were statistically significantly lower in group 3, 5 and 6 compared to group 2 (p < 0.05). There was no statistically difference between VEGF ELISA levels of group 2 and 4 (p > 0.05). CONCLUSIONS: Sorafenib was as effective as bevacizumab in the regression of corneal neovascularization. The effect of sorafenib seems to be dose-dependent. The low doses and twice a day administration are important advantages of sorafenib.

Mango ginger (curcuma amada) inhibits collagen-induced arthritis by modulating inflammatory cytokine levels in rats

Background/aim: Mango ginger (MG: curcuma amada) has antioxidant and antiinflammatory activities. The aim was to evaluate the antiarthritic potential efficacy of MG on collagen-induced arthritis. Materials and methods: Twenty-one female Wistar-albino rats were divided into three groups. Arthritis was induced by intradermal injections of type II collagen and Freund's adjuvant. MG extract was orally administered starting from the first collagen injection. TNF-α, IL-6, IL-17, obestatin, sclerostin, and DKK-1 serum levels were determined, and perisynovial inflammation and cartilage-bone destruction in the paws were histologically evaluated. Moreover, joint tissue TNF-α, IL-17, NF-κB, and COX-2 levels were analyzed. Results: TNF-α, IL-17, IL-6, and DKK-1 serum levels were increased, and obestatin and sclerostin serum levels were decreased in the arthritis group compared to the control group. However, MG supplements decreased TNF-α, IL-17, IL-6, and DKK-1 serum levels and increased obestatin and sclerostin serum levels. Similarly, while collagen injection increased tissue TNF-α, IL-17, NF-κB, and COX-2 levels, MG decreased TNF-α, IL-17, and NF-κB levels. Moreover, MG ameliorated perisynovial inflammation and cartilage-bone destruction in the paws. Conclusion: MG ameliorates arthritis via actions on inflammatory ways and wingless (Wnt) signaling pathway. These results suggest that MG may have a considerable potential efficacy for the treatment of rheumatoid arthritis.

Is there any potential anticancer effect of raloxifene and fluoxetine on DMBA-induced rat breast cancer?

Breast cancer is the most common cancer among women in the world and the incidence is increasing alarmingly. It was aimed to determine the effect of raloxifene (RAL) and fluoxetine (FLX) on selected parameters in 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma. Thirty-two female Wistar albino rats were assorted into four groups: DMBA (group I), DMBA+RAL (group II), DMBA+FLX (group III), and DMBA+RAL+FLX (group IV). Mammary tissue vascular endothelial growth factor (VEGF), macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-9 (MMP-9), and tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) levels were determined by the enzyme-linked immunosorbent assay method. The tissue VEGF levels were lower in group IV compared with DMBA group. Decreased M-CSF levels were observed in all therapeutic groups rather than the DMBA group, but the most effective decrease was found in group IV. Compared with the DMBA group, MMP-9 levels were statistically significantly decreased in group II and group IV. However, TIMP-1 levels were higher in the whole therapeutic groups rather than the DMBA group and the most effective increase was observed in group IV. Results of the present study suggest that combined therapy of RAL with FLX might lead to a better outcome targeting breast tumor.

Effects of allyl isothiocyanate on insulin resistance, oxidative stress status, and transcription factors in high-fat diet/streptozotocin-induced type 2 diabetes mellitus in rats.

Allyl isothiocyanate (AITC), a dietary phytochemical found in some cruciferous vegetables, is commonly used as an antimicrobial, anticancer, and antioxidant agent. In the present study, we investigated the effects of AITC on insulin resistance and transcription factors in a diabetic rat model. A total of 42 Wistar rats were divided into six groups and orally treated for 12 weeks as follows: (i) control; (ii) AITC (100 mg/kg body weight [BW]); (iii) high fat diet (HFD); (iv) HFD + AITC (100 mg/kg BW); (v) HFD + streptozotocin (STZ, 40 mg/kg BW); and (vi) HFD + STZ + AITC. Administration of AITC reduced blood glucose, total cholesterol, triglycerides, and creatinine levels, but increased (P < 0.001) total antioxidant capacity. In AITC-treated rats, the glucose transporter-2, peroxisome proliferator-activated receptor gamma, p-insulin receptor substrate-1, and nuclear factor erythroid-derived 2 in the liver and kidney were increased while nuclear factor-kappa B was downregulated (P < 0.05). In conclusion, AITC possesses antidiabetic, antioxidant, and anti-inflammatory activities in HFD/STZ-induced T2DM in rats. These findings may further justify the importance of AITC in phytomedicine.

(3R, 3'R)-zeaxanthin protects the retina from photo-oxidative damage via modulating the inflammation and visual health molecular markers.

PURPOSE: Zeaxanthin protects the macula from ocular damage due to light or radiation by scavenging harmful reactive oxygen species. In the present study, zeaxanthin product (OmniXan®; OMX), derived from paprika pods (Capsicum annum; Family-Solanaceae), was tested for its efficacy in the rat retina against photooxidation. METHODS: Forty-two male 8-week-old Wistar rats exposed to 12L/12D, 16L/8D and 24L/0D hours of intense light conditions were orally administrated either 0 or 100 mg/kg BW of zeaxanthin concentration. Retinal morphology was analyzed by histopathology, and target gene expressions were detected with real-time polymerase chain reaction methods. RESULTS: OMX treatment significantly increased the serum zeaxanthin concentration (p < 0.001) and ameliorated oxidative damage by increasing the antioxidant enzyme activities in the retina induced by light (p < 0.001). OMX administration significantly upregulated the expression of genes, including Rhodopsin (Rho), Rod arrestin (SAG), Gα Transducin 1 (GNAT-1), neural cell adhesion molecule (NCAM), growth-associated protein 43 (GAP43), nuclear factor-(erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase (HO-1) and decreased the expression of nuclear factor-κB (NF- κB) and GFAP by OMX treatment rats. The histologic findings confirmed the antioxidant and gene expression data. CONCLUSIONS: This study suggests that OMX is a potent substance that can be used to protect photoreceptor cell degeneration in the retina exposed to intense light.

Intratumoral Cytotoxic T-Lymphocyte Density and PD-L1 Expression Are Prognostic Biomarkers for Patients with Colorectal Cancer.

Background and objectives: Cytotoxic T-lymphocyte (CTL)-mediated inflammatory response to tumors plays a crucial role in preventing the progression of some cancers. Programmed cell death ligand 1 (PD-L1), a cell-surface glycoprotein, has been reported to repress T-cell-mediated immune responses against tumors. However, the clinical significance of PD-L1 in colorectal cancer (CRC) remains unclear. Our aim was to elucidate the prognostic significance of PD-L1 expression and CD8+ CTL density in CRC. Materials and methods: CD8 and PD-L1 immunostaining was conducted on 157 pathologic specimens from patients with CRC. The CD8+ CTL density and PD-L1 expression within the tumor microenvironment were assessed by immunohistochemistry. Results: Tumor invasion (pT) was significantly correlated with intratumoral (p = 0.011) and peritumoral (p = 0.016) CD8+ CTLs density in the tumor microenvironment. In addition, there was a significant difference in the intensity of CD8+ CTLs between patients with and without distant metastases (intratumoral p = 0.007; peritumoral p = 0.037, T-test). Lymph node metastasis (pN) and TNM stage were significantly correlated with PD-L1 expression in CRC cells (p = 0.015, p = 0.029, respectively). Multivariate analysis revealed a statistically significant relationship between the intratumoral CD8+ CTL density and disease-free survival (DFS) (hazard ratio [HR] 2.06; 95% confidence interval [CI]: 1.01-4.23; p = 0.043). The DFS was considerably shorter in patients with a high expression of PD-L1 in cancer cells than those with a low expression (univariate HR 2.55; 95% CI 1.50-4.34; p = 0.001; multivariate HR 0.48; 95% CI 0.28-0.82; p = 0.007). Conversely, patients with high PD-L1 expression in tumor-infiltrating lymphocytes had a longer DFS in both univariate analysis (HR 0.25; 95% CI: 0.14-0.44; p < 0.001) and multivariate analysis (HR 3.42; 95% CI: 1.95-6.01; p < 0.001). Conclusion: The CD8+ CTL density and PD-L1 expression are prognostic biomarkers for the survival of patients with CRC.

LFM-A13, a potent inhibitor of polo-like kinase, inhibits breast carcinogenesis by suppressing proliferation activity and inducing apoptosis in breast tumors of mice.

The goals of the present study were to define the anticancer activity of LFM-A13 (α-cyano-ß-hydroxy-ß-methyl-N-(2,5-dibromophenyl)-propenamide), a potent inhibitor of Polo-like kinase (PLK), in a mouse mammary cancer model induced by 7,12-dimethylbenz(a)anthracene (DMBA) in vivo and explore its anticancer mechanism(s). We also examined whether the inhibition of PLK by LFM-A13 would improve the efficiency of paclitaxel in breast cancer growth in vivo. To do this, female BALB/c mice received 1 mg of DMBA once a week for 6 weeks with oral gavage. LFM-A13 (50 mg/kg body weight) was administered intraperitoneally with DMBA administration and continued for 25 weeks. We found that LFM-A13, paclitaxel, and their combination have a significant effect on the DMBA-induced breast tumor incidence, mean tumor numbers, average tumor weight, and size. At the molecular level, the administration of LFM-A13 hindered mammary gland carcinoma development by regulating the expression of PLK1, cell cycle-regulating proteins cyclin D1, cyclin dependent kinase-4 (CDK-4), and the CDK inhibitor, p21. Moreover, LFM-A13 treatment upregulated the levels of IκB, the pro-apoptotic proteins Bax, and caspase-3, and down-regulated p53 and the antiapoptotic protein Bcl-2 in mammary tumors. The combination of LFM-A13 with paclitaxel was found to be more effective compared with either agent alone. Collectively, these results suggest that LFM-A13 has an anti-proliferative activity against breast cancer in vivo and that LFM-A13 and paclitaxel combination could be a strategy for the treatment of breast cancer.

Octreotide ameliorates dermal fibrosis in bleomycin-induced scleroderma

Background/aim: Insulin-like growth factor (IGF)-I is a differentiation and growth factor. Antifibrotic action of octreotide has been reported in pulmonary fibrosis. The present study aimed to research the prophylactic and therapeutic potential of octreotide on a bleomycin (BLM)-induced experimental scleroderma model. Materials and methods: Sixty Balb/c female mice were divided into 6 groups. Daily subcutaneous BLM (100 µg) was injected for 3 weeks in groups II and III and for 6 weeks in groups V and VI. Octreotide (100 µg/kg per day) was injected subcutaneously for the first 3 weeks in group III (prophylactic) and the second 3 weeks in group VI (therapeutic). Mice in groups I, II, and III were sacrificed at the end of the third week, while mice in groups IV, V, and VI were sacrificed at the end of the sixth week. Results: Repeated BLM applications increased dermal inflammatory cell counts and dermal thickness, and led to dermal fibrosis at both the third and sixth weeks. Moreover, mRNA expressions of TGF-ß1 and IGF binding protein (IGFBP)-3 and -5 were higher in the BLM- injected sham groups. On the other hand, IGFBP-3 and -5 mRNA expressions were significantly decreased in both the prophylactic and therapeutic octreotide groups. Similarly, octreotide decreased dermal inflammatory infiltrations and dermal thickness. Conclusion: Octreotide has antifibrotic actions on experimentally induced dermal fibrosis. It can be suggested that IGF-I plays pathogenic roles, and octreotide is a candidate for research in the treatment of scleroderma.

Paricalcitol inhibits the Wnt/beta-catenin signaling pathway and ameliorates experimentally induced arthritis

Background/aim: The Wnt/ß-catenin pathway has important biological activities, including the differentiation of cells and joint formations. The aim of our study was to determine the effect of paricalcitol on experimentally induced arthritis. Materials and methods: Type II collagen combined with Freund's adjuvant was applied to induce arthritis in Wistar albino female rats. Paricalcitol (0.3 µg/kg daily) was subcutaneously injected starting 1 day after collagen applications (prophylactic group) or 1 day after the onset of arthritis (therapeutic group), until day 29. Results: The 29th day arthritis scores were lower compared to the 13th day scores in the paricalcitol groups (P < 0.05), while they were higher in the arthritis group (P < 0.05). Marked cartilage-bone destruction and extensive perisynovial inflammation were detected in the arthritis group. Decreased cartilage-bone destruction and perisynovial inflammation in the paws were observed in the paricalcitol groups. The tissue mRNA levels of DKK1, Wnt5a, and axin-2 were higher in the arthritis group than in the control group. In the paricalcitol groups, mRNA expressions were lower than in the arthritis group. Conclusion: The present study shows that the Wnt/ß-catenin signaling pathway is active in arthritis. Moreover, paricalcitol ameliorates arthritis via inhibiting the Wnt/ß-catenin pathway. Paricalcitol and the Wnt/ß-catenin pathway are candidates for research in human rheumatoid arthritis.

Genetic polymorphism of antioxidant enzymes in eosinophilic and non-eosinophilic nasal polyposis.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the paranasal sinuses, and its pathophysiology is not yet precisely known. It is suggested that oxygen free radicals play an important role in the pathogenesis of nasal polyposis. This study aimed to identify genetic polymorphisms of superoxide dismutase (SOD 2), catalase (CAT), and inducible nitric oxide synthase (iNOS) enzymes in eosinophilic CRSwNP and non-eosinophilic CRSwNP patients; the study also aimed to evaluate the effect of genetic polymorphism of antioxidant enzymes on CRSwNP etiopathogenesis. One hundred thirty patients, who received endoscopic sinus surgery due to CRSwNP, and 188 control individuals were included in this study. Nasal polyp tissues were divided into two groups histopathologically as eosinophilic CRSwNP and non-eosinophilic CRSwNP. Venous blood samples were taken from the patient and control groups. Polymorphisms in the Ala16Va1 gene, which is the most common variation of SOD-2 gene, and 21 A/T polymorphisms in catalase gene were evaluated with the restriction fragment length polymorphism method and -277 C/T polymorphism in the iNOS gene was evaluated with the DNA sequencing method. The GG genotype distribution for the (-277) A/G polymorphism in the iNOS gene was a statistically significant difference between eosinophilic CRSwNP and control groups (p < 0.05). The CC genotype distribution for the SOD2 A16V (C/T) polymorphism was not statistically significant in all groups (p > 0.05). The TT genotype distribution for the A/T polymorphism in catalase gene at position -21 was statistically significant differences in eosinophilic CRSwNP and control groups (p < 0.05). Increased free oxygen radical levels, which are considered effective factors in the pathogenesis of CRSwNP, can occur due to genetic polymorphism of enzymes in the antioxidant system and genetic polymorphism of antioxidant enzymes in eosinophilic CRSwNP patients might contribute to the pathophysiology.

Effects of Mucuna pruriens on Free Fatty Acid Levels and Histopathological Changes in the Brains of Rats Fed a High Fructose Diet.

OBJECTIVE: To investigate free fatty acid levels and histopathological changes in the brain of rats fed a high fructose diet (HFrD) and to evaluate the effects of Mucuna pruriens, known to have antidiabetic activity, on these changes. MATERIALS AND METHODS: The study comprised 28 mature female Wistar rats. The rats were divided into 4 groups, each included 7 rats. Group 1: control; group 2: fed an HFrD; group 3: fed normal rat chow and M. pruriens; group 4: fed an HFrD and M. pruriens for 6 weeks. At the end of 6 weeks, the rats were decapitated, blood and brain tissues were obtained. Serum glucose and triglyceride levels were measured. Free fatty acid levels were measured in 1 cerebral hemisphere of each rat and histopathological changes in the other. The Mann-Whitney U test was used to compare quantitative continuous data between 2 independent groups, and the Kruskal-Wallis test was used to compare quantitative continuous data between more than 2 independent groups. RESULTS: Arachidonic acid and docosahexaenoic acid levels were significantly higher in group 2 than in group 1 (p < 0.05). Free arachidonic acid and docosahexaenoic acid levels in group 4 were significantly less than in group 2 (p < 0.05). Histopathological examination of group 2 revealed extensive gliosis, neuronal hydropic degeneration, and edema. In group 4, gliosis was much lighter than in group 2, and edema was not observed. Neuronal structures in group 4 were similar to those in group 1. CONCLUSIONS: The HFrD increased the levels of free arachidonic acid and docosahexaenoic acid probably due to membrane degradation resulting from possible oxidative stress and inflammation in the brain. The HFrD also caused extensive gliosis, neuronal hydropic degeneration, and edema. Hence, M. pruriens could have therapeutic effects on free fatty acid metabolism and local inflammatory responses in the brains of rats fed an HFrD.

Comparative evaluation of the sexual functions and NF-κB and Nrf2 pathways of some aphrodisiac herbal extracts in male rats.

BACKGROUND: Mucuna pruriens, Tribulus terrestris and Ashwagandha (Withania somnifera) are widely known as antioxidant effective herbals and have been reported to possess aphrodisiac activities in traditional usages. In this study, we determined the effects of these herbals on sexual functions, serum biochemical parameters, oxidative stress and levels of NF-κB, Nrf2, and HO-1 in reproductive tissues. METHODS: Thirty-five male rats were divided into five groups: the control group, sildenafil-treated group (5 mg/kg/d), Mucuna, Tribulus and Ashwagandha groups. The extract groups were treated orally either with Mucuna, Tribulus or Ashwagandha (300 mg/kg b.w.) for 8 weeks. RESULTS: All of the extracts were found to be significantly effective in sexual functioning and antioxidant capacity and Tribulus showed the highest effectiveness. Serum testosterone levels significantly increased in Tribulus and Ashwagandha groups in comparison to control group. Tribulus was able to reduce the levels of NF-κB and increase the levels of Nrf2 and HO-1 to a much greater extent than Mucuna and Ashwagandha. CONCLUSIONS: These results demonstrate for the first time that Mucuna, Tribulus and Ashwagandha supplementation improves sexual function in male rats via activating Nrf2/ HO-1 pathway while inhibiting the NF-κB levels. Moreover, Tribulus terrestris extract was found to be more bioavailable from Ashwagandha extract followed by Mucuna extract. Schematic representation of the mode of action of some aphrodisiac herbal extracts to improve sexual functions.