The Effect of Spironolactone on ß-amyloid-Induced Memory Impairment in Male Rats: The Role of Microglial Inhibition.

Purpose: Neuroinflammation was indicated in the pathophysiology of Alzheimer's disease (AD). Previous reports have also signified that spironolactone has anti-inflammatory effects. Therefore, the aim of this study was to assess the modulatory effects of spironolactone on neuroinflammation and memory loss in a rat model of AD. Methods: The ß-amyloid protein fragment 25-35 (Aß) was injected in the dorsal hippocampus (5 µg/2.5 µL each side) of male Sprague-Dawley rats for four consecutive days to induce memory impairment. Animals have intraperitoneally received spironolactone (10, 25, or 50 mg/kg, N = 6/ group) or vehicle for 14 days. The passive inhibitory avoidance and the novel recognition tests were used for memory evaluation. Neuroinflammation was assessed by measuring the level of Iba1 protein, a marker of microglial activation, using western immunoblotting. Results: Different doses of spironolactone showed no significant changes in latency times and discriminations ratios in passive inhibitory avoidance and novel recognition tests, respectively, as compared to vehicle. However, spironolactone-treated groups showed significantly lower Iba1 protein levels in comparison to the vehicle-treated group (P < 0.01). Conclusion: Spironolactone had a modulatory effect on neuroinflammation through a repressive effect on microglial activation with no valuable effect on memory improvement in a rat model of AD. The findings of this study suggest that Aß-induced memory loss may not be directly linked to microglial activation. Spironolactone may be a potential candidate to be examined in other neuroinflammatory disorders.

Photocatalytic TiO2@MIL-88A (Fe)/polyacrylonitrile mixed matrix membranes: Characterization, anti-fouling properties, and performance on the removal of natural organic matter.

Photocatalytic membrane reactors (PMRs), coupling photocatalysts and membranes in a single system, have shown a considerable potential to reduce membrane fouling, which is one of the major drawbacks of using membranes to treat water and wastewater. In this study, the visible light-activated photocatalysts were incorporated into the polyacrylonitrile (PAN) casting solution to synthesize the photocatalytic composite membranes. The physicochemical properties and the morphology of the membranes and photocatalysts were characterized by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction analysis (XRD), ultraviolet-visible diffuse reflectance spectroscopy (UV-visible DRS), photoluminescence (PL), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), Brunauer-Emmett-Teller (BET), porosimetry, and contact angle analyses. The performance of the synthesized photocatalytic mixed matrix membranes (MMMs) in treating water containing humic acid, as one of the major components in natural organic matter (NOM) existing in drinking water sources, was investigated. Under visible light irradiation, the PAN/TiO2@MIL-88A (Fe) MMMs simultaneously adopted photocatalysis and membrane separation in the PMR and thereby enhanced humic acid removal and anti-fouling properties. The best synthesized photocatalytic membrane could remove 92.4% of the humic acid once exposed to visible light. The optimum membrane had suitable water permeability, a high flux recovery ratio (99.5%), and a 13.5% decline in the humic acid flux after a 10-h run, considerably lower compared to the corresponding decline of the pristine membrane (37.5% over the same period). The remarkable properties of the PAN/TiO2@MIL-88A (Fe) membrane, including its high anti-fouling specification, confirm the appropriateness of the synthesized MMM for treating water involving humic acid.

Contribution of Lysosome and Sigma Receptors to Neuroprotective Effects of Memantine Against Beta-Amyloid in the SH-SY5Y Cells.

Purpose: Memantine is an approved drug for the treatment of Alzheimer's disease (AD). Autophagy, lysosome dysfunction, and sigma receptors have possible roles in the pathophysiology of AD. Therefore, we aimed to investigate the contribution of sigma receptors and lysosome inhibition to the neuroprotective effects of memantine against amyloid-beta (Aß)-induced neurotoxicity in SH-SY5Y cells. Methods: We determined the neuroprotective effects of memantine (2.5 µM), dizocilpine (MK801, as a selective N-methyl-D-aspartate (NMDA) receptor antagonist) (5 µM) against Aß25- 35 (2 µg/µL)-induced neurotoxicity. We used chloroquine (10, 20, and 40 µM) as a lysosome inhibitor and BD-1063 (1, 10, and 30 µM) as a selective sigma receptor antagonist. The MTT assay was used to measure the neurotoxicity in the SH-SY5Y cells. Data were analyzed using the one-way ANOVA. Results: Memantine (2.5 µM), dizocilpine (5 µM), chloroquine (10 and 20 µM) and BD-1063 (1, 10 and 30 µM) decreased the neurotoxic effects of Aß on the SH-SY5Y cells. However, chloroquine (40 µM) increased the neurotoxic effects of Aß. Cell viability in the cells treated with memantine + Aß + chloroquine (10, 20, and 40 µM) was significantly lower than the memantine + Aß-treated group. Moreover, cell viability in the memantine + Aß group was higher than the memantine + Aß + BD-1063 (10 and 30 µM) groups. Conclusion: The lysosomal and sigma receptors may contribute to the neuroprotective mechanism of memantine and other NMDA receptor antagonists. Moreover, the restoration of lysosomes function and the modulation of sigma receptors are potential targets in the treatment of AD.

Protective effect of standardized extract of Myrtus communis L. (myrtle) on experimentally bleomycin-induced pulmonary fibrosis: biochemical and histopathological study.

CONTEXT: Myrtle (Myrtus communis L) has been used widely in traditional medicine for different respiratory disorders. Idiopathic pulmonary fibrosis (IPF) is an inflammatory disease characterized by progressive loss of lung function with poor prognosis. The pathogenesis of disease has not been completely elucidated, but probably persistent epithelial damages are involved. OBJECTIVE: Evaluation of biochemical and histopathological effect of preventive and therapeutic doses of myrtle against bleomycin (BLM)-induced pulmonary fibrosis (PF) in animal model. MATERIALS AND METHODS: Methanolic extract of M. communis was prepared by maceration method. Total flavonoid content was determined and experimentally PF was induced in rat with intratracheal instillation of a single dose of BLM (5 mg/kg) only on day 0. Myrtle antifibrotic effect was evaluated as preventive (50 mg/kg/day, intraperitoneal (i.p.) injection, from day 0-13) and therapeutic agent (50 mg/kg, i.p., from day 14-27) in comparison with methyl prednisolone (M-pred) (4 mg/kg, i.p. for 14 days). RESULTS: Parenchymal inflammation and fibrotic changes significantly were reduced by myrtle and M-pred. Significant decrease in hydroxyproline content and lipid peroxidation were observed in animals receiving myrtle extract while catalase activity was increased by myrtle. Improvement in inflammation and fibrosis was observed in myrtle group especially in the early phase of fibrosis (preventive regime). DISCUSSION AND CONCLUSION: Myrtle extract effectively inhibited the inflammation and fibrosis of lung parenchyma in both preventive and therapeutic methods. This effect might be due to the reduction of tissue inflammation and inhibition of oxidative stress. More studies are being carried out to find main mechanisms and separation of active compounds.

Anti-Inflammatory Subfractions Separated from Acidified Chloroform Fraction of Fenugreek Seeds (Trigonella foenum-graecum L.).

Considering the side effects of current anti-inflammatory drugs, novel therapeutic agents are desired. We have succeeded in separating flavonoid-rich fractions with anti-inflammatory effect from fenugreek seeds (Trigonella foenum-graecum L.). In this work, we aimed to carry out further fractionation to find active anti-inflammatory subfractions. Trigonelline content of the plant was determined by spectrophotometric method. Fenugreek seeds were extracted consecutively with petroleum ether, acidified chloroform (ACC), alkaline chloroform (AKC), methanol, and water. ACC fraction, which had exhibited the highest anti-inflammatory effect, was further fractionated using column chromatography. Obtained subfractions were evaluated using carrageenan-induced paw edema (CIPE) method. Animals were pretreated by test compounds, and after 30 minutes edema was induced by subcutaneous injection of 100 µl of 1% w/v carrageenan into the right paw of animals. Volume difference of both paws was measured at different times after carrageenan injection. The concentration of trigonelline was determined as 16.2%. ACC fraction inhibited paw edema significantly in comparison to control (p < .05). Four subfractions (dry weight percentage basis) were selected for pharmacological study. F3 subfraction exhibited the greatest inhibition at 15 mg/kg (p < .001). ACC fraction and F4 significantly inhibited paw edema at doses of 5, 10, and 15 mg/kg (p < .001). Phytochemical studies indicated the presence of flavonoids in ACC and active subfractions. Further separation can lead to finding active components from active subfractions, which probably belong to flavonoid phytochemicals. Considering the gastroprotective effect of fenugreek, we hope the separated fractions also would be free of gastrointestinal side effects.

Accelerated Burn Wound Closure in Mice with a New Formula Based on Traditional Medicine.

BACKGROUND: A combination of the oils of sesame, hemp, wild pistachio, and walnut has been used for treatment of skin disorders, including wound burns, in some parts of Kerman, Iran. Evaluation of this remedy in the form of a pharmaceutical formulation in animal models can pave the way for its future application in wound burn healing in humans. OBJECTIVES: This experimental study investigated the healing potential of a new formula (NF) based on folk medicine from Iran for the treatment of third degree burns in mice. The formula was a combination of the oils of four plants: sesame (Sesamum indicum L.), wild pistachio (Pistacia atlantica Desf.), hemp (Cannabis sativa L.), and walnut (Juglans regia L.). METHODS: Twenty-four mice were selected based on simple random sampling. Twenty-five percent of the total body surface area was burned by exposure to boiling water, according to the Walker-Mason method. NF and silver sulfadiazine (the positive control) were applied topically twice a day for 21 days. The burned area in the negative control group was left untreated. Epithelialization time and the percent of wound contraction were measured during the treatment period. The process of wound repairing was evaluated using histological (H and E and trichrome staining) and immunohistological (anti-pancytokeratin) methods. RESULTS: When compared to the controls, NF significantly improved wound contraction after day 10. Epithelialization time in the NF group was significantly faster than in the other groups (20 vs. 25.5 days) (P < 0.001). Histopathological and immunohistochemical findings confirmed the efficacy of the NF. CONCLUSIONS: A new therapeutic remedy was introduced for the treatment of burn wounds. Further clinical and molecular studies are suggested to determine the exact mechanism(s) involved in the burn wound healing effect of NF.

Investigation of association between donors' and recipients' NADPH oxidase p22(phox) C242T polymorphism and acute rejection, delayed graft function and blood pressure in renal allograft recipients.

BACKGROUND: Production of reactive oxygen species (ROS) and thereby induction of oxidative stress seem to be one of the major mediators of inflammatory adverse outcomes after renal transplantation. p22(phox) is a polymorphic subunit of NAD(P)H-oxidase that is critical for activation and stabilization of the enzyme. This enzyme is involved in the production of superoxide that triggers inflammatory injuries to the kidney. So in this study, the association between donors and recipients' C242T polymorphism of p22(phox) and acute rejection (AR), delayed graft function (DGF), creatinine clearance (CrCl), and blood pressure in renal-allograft recipients was studied. METHODS: One hundred ninety six donor-recipient pairs were studied. The C242T polymorphism of p22(phox) was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). According to p22 genotype, the subjects were divided in wild-type (CC) and T allele carriers (CT+TT). Transplantation outcomes were determined using acute rejection and delayed graft function criteria. The mean arterial pressure was also measured monthly after transplantation. RESULTS: There was a significant association between the recipients' p22(phox) polymorphism and DGF occurrence (OR=2.5, CI: 1.2-4.9, p=0.0009). No significant association was detected between donors' p22(phox) polymorphism and AR and DGF events. CrCl during the six months follow-up after transplantation was lower in the patients who received allograft from donors carrying 242T allele (B=-12.8, CI: -22.9-12.8 (-22.9 to -2.6)). Changes in the blood pressure were not different among the patients having different genotypes of p22(phox). CONCLUSION: These results suggest that the recipients' p22(phox) C242T polymorphism may be a major risk factor for DGF in renal transplantation. Moreover, the donors' 242T allele seems to affect the rate of CrCl in the renal allograft recipients.