Scutellarin alleviates lipopolysaccharide-provoked septic nephrotoxicity via attenuation of inflammatory and oxidative events and mitochondrial dysfunction.

BACKGROUND: Sepsis-associated acute kidney injury (AKI) is highlighted by high incidence of mortality and morbidity. Scutellarin is a flavone extracted from certain medicinal plants with anti-inflammatory and anti-oxidative properties. This research study was done to investigate the beneficial effect of scutellarin on lipopolysaccharide (LPS) murine model of AKI. MATERIALS AND METHODS: Five groups of mice were used including control (without LPS injection), LPS group (LPS injection, 10 mg/kg), and LPS + Scutellarin25, 50, and/or 100 groups (receiving scutellarin orally at different doses of 25, 50, or 100 mg/kg before LPS injection). RESULTS: Scutellarin pretreatment effectively lowered kidney function markers (BUN, creatinine, and cystatin C), improved superoxide dismutase (SOD) besides enhancement of level, and/or gene expression for nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) and also reduced oxidative stress factors including reactive oxygen species (ROS) and malondialdehyde (MDA). In addition, scutellarin reduced tissue level and/or gene expression of inflammatory markers comprising toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-κB), and tumor necrosis factor α (TNF-α) and properly raised anti-inflammatory factor IL-10. Moreover, scutellarin enhanced mitochondrial membrane potential (MMP) and attenuated histopathological changes in renal tissue subsequent to LPS challenge. Beneficial effects of scutellarin was associated with improvement of gene expression regarding peroxisome proliferator-activated receptor gamma (PPARγ) and its coactivator PGC-1α as specific markers of mitochondrial biogenesis. CONCLUSION: These results indicate that scutellarin could protect against LPS-provoked AKI through restraining inflammation and oxidative stress and maintenance of mitochondrial health and biogenesis which is partly mediated through its regulation of Nrf2/PPAR-γ/PGC-1α/NF-kB/TLR4.

S-allyl cysteine, an active ingredient of garlic, attenuates acute liver dysfunction induced by lipopolysaccharide/ d-galactosamine in mouse: Underlying mechanisms.

In the present study, beneficial effect of S-allyl cysteine (SAC) was evaluated in the lipopolysaccharide/d-galactosamine (LPS/d-Gal) model of acute liver injury (ALI). To mimic ALI, LPS and d-Gal (50 µg/kg and 400 mg/kg, respectively) were intraperitoneally administered and animals received SAC per os (25 or 100 mg/kg/d) for 3 days till 1 hour before LPS/d-Gal injection. Pretreatment of LPS/d-Gal group with SAC-lowered activities of alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase and partially reversed inappropriate alterations of hepatic oxidative stress- and inflammation-related biomarkers including liver reactive oxygen species, malondialdehyde, and hepatic activity of the defensive enzyme superoxide dismutase, ferric reducing antioxidant power (FRAP), toll-like receptor-4 (TLR4), cyclooxygenase 2, NLR family pyrin domain containing 3 (NLRP3), caspase 1, nuclear factor κB (NF-κB), interleukin 1ß (IL-1ß), IL-6, tumor necrosis factor-α, and myeloperoxidase activity. Additionally, SAC was capable to ameliorate apoptotic biomarkers including caspase 3 and DNA fragmentation. In summary, SAC can protect liver against LPS/d-Gal by attenuation of neutrophil infiltration, oxidative stress, inflammation, apoptosis, and pyroptosis which is partly linked to its suppression of TLR4/NF-κB/NLRP3 signaling.

Soy isoflavone genistein attenuates lipopolysaccharide-induced cognitive impairments in the rat via exerting anti-oxidative and anti-inflammatory effects.

Systemic inflammation during infectious disorders usually accompanies chronic complications including cognitive dysfunction. Neuroinflammation and cognitive deficit are also observed in some debilitating neurological disorders like Alzheimer's and Parkinson's diseases. Genistein is a soy isoflavone with multiple beneficial effects including anti-inflammatory, anti-oxidative, and protective properties. In this research study, the effect of genistein in prevention of lipopolysaccharide (LPS)-induced cognitive dysfunction was investigated. LPS was given i.p. (500 µg/kg/day) and genistein was orally given (10, 50, or 100 mg/kg) for one week. Findings showed that genistein could dose-dependently attenuate spatial recognition, discrimination, and memory deficits. Additionally, genistein treatment of LPS-challenged group lowered hippocampal level of malondialdehyde (MDA) and increased activity of superoxide dismutase (SOD) and catalase and glutathione (GSH) level. Furthermore, genistein ameliorated hippocampal acetylcholinesterase (AChE) activity in LPS-challenged rats. Furthermore, genistein administration to LPS-injected group lowered hippocampal level of interleukin 6 (IL-6), nuclear factor-kappaB (NF-κB) p65, toll-like receptor 4 (TLR4), tumor necrosis factor α (TNFα), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), glial fibrillary acidic protein (GFAP), and increased hippocampal level of antioxidant element nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In conclusion, genistein alleviated LPS-induced cognitive dysfunctions and neural inflammation attenuation of oxidative stress and AChE activity and appropriate modulation of Nrf2/NF-κB/IL-6/TNFα/COX2/iNOS/TLR4/GFAP.

Protective effect of sesamin in lipopolysaccharide-induced mouse model of acute kidney injury via attenuation of oxidative stress, inflammation, and apoptosis.

CONTEXT: Acute kidney injury (AKI) is considered a major public health concern in today's world. Sepsis-induced AKI is large as a result of exposure to lipopolysaccharide (LPS) that is the major outer membrane component of Gram-negative bacteria. Sesamin is the main lignan of sesame seeds with multiple protective effects. OBJECTIVE: In this research, we tried to demonstrate the protective effect of sesamin pretreatment in LPS-induced mouse model of AKI. METHODS: LPS was injected at a single dose of 10 mg/kg (i.p.) and sesamin was given p.o. at doses of 25, 50, or 100 mg/kg, one hour prior to LPS. RESULTS: Treatment of LPS-challenged mice with sesamin reduced serum level of creatinine and blood urea nitrogen (BUN) and returned back renal oxidative stress-related parameters including glutathione (GSH), malondialdehyde (MDA), and activity of catalase and superoxide dismutase (SOD). Moreover, sesamin alleviated inappropriate changes of renal nuclear factor-kappaB (NF-κB), toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX2), tumor necrosis factor α (TNFα), interleukin-6, DNA fragmentation (an apoptotic index), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In addition, sesamin diminished magnitude of kidney tissue damage due to LPS. CONCLUSION: In summary, sesamin could dose-dependently abrogate LPS-induced AKI via attenuation of renal oxidative stress, inflammation, and apoptosis.

New pressure-assisted sweeping on-line preconcentration for highly polar environmentally relevant nitrosamines: Part 2. Cationic and anionic surfactants with zero-flow capillaries.

We recently introduced a pressure-assisted sweeping-reversed migration-EKC (RM-EKC) method for preconcentration of neutral polar N-nitrosamines with low affinity for the micellar phase. The type of surfactant and phase ratio are dominant factors in dictating the magnitude of interactions between analyte and micellar phase, thus four surfactants (anionic and cationic) with a range of functionalities (SDS, ammonium perfluorooctanoate (APFO), bile salts, and cetyltrimethylammonium chloride (CTAC)) were evaluated for sweeping-RM-EKC of highly polar N-nitrosamines. All gave acceptable results for sweeping-RM-EKC when used in high concentrations (≥200 mM) with low EOF. While no single surfactant was superior by all measures, all but the bile salts had useful performance characteristics. APFO showed the narrowest peak widths and highest number of theoretical plates, though two species co-migrated at all concentrations (25-300 mM); SDS and the cationic surfactant CTAC also showed good separation characteristics and could resolve all peaks, but CTAC had wider separation window. Various types of capillaries coated for EOF control were compared for use with anionic and cationic surfactants. A commercial zero-EOF capillary coated with a polymer bearing sulfonic acid functional groups showed superior EOF suppression and reproducibility of migration time with all surfactants.

How the combination of alginate and chitosan can fabricate a hydrogel with favorable properties for wound healing.

Wound management has always been a significant concern, particularly for men, and the search for effective wound dressings has led to the emergence of hydrogels as a promising solution. In recent years, hydrogels, with their unique properties, have gained considerable importance in wound management. Among the various types of hydrogels, those incorporating chitosan and alginate, two distinct chemical materials, have shown potential in accelerating wound healing. This review aims to discuss the desirable characteristics of an effective wound dressing, explore the alginate/chitosan-based hydrogels developed by different researchers, and analyze their effects on wound healing through in vitro and in vivo assessments. In vitro tests encompass a wide range of evaluations, including swelling capacity, degradation rate, porosity, Fourier Transform Infrared Spectroscopy, X-ray diffraction analysis, moisture vapor transmission rate, release studies, mechanical properties, microscopic observation, antibacterial properties, compatibility assessment, cell adhesion investigation, blood clotting capability, cell migration analysis, water contact angle determination, and structural stability. Furthermore, in vivo assessments encompass the examination of wound closure rate, modulation of gene expression, as well as histopathological and immunohistochemical studies.

Protective effect of sinomenine against CCl4-induced acute liver injury through regulation of mitochondrial biogenesis.

Carbon tetrachloride (CCl4)-provoked acute liver injury (ALI) is typified by intensified apoptotic, inflammatory, and oxidative changes besides mitochondrial dysfunction. Sinomenine is an active constituent in the medicinal plant Sinomenium acutum. The main objective of this study was to determine sinomenine-induced hepatoprotection following CCl4 challenge with an emphasis on unraveling the contribution of mitochondrial biogenesis-related factors. To induce ALI, CCl4 was injected i.p. and sinomenine was orally administered at 10, 25, and 50 mg/kg. Serum factors in relation to liver dysfunction were measured in addition to hepatic analysis of apoptotic, mitochondrial biogenesis, oxidative, and inflammatory parameters. Sinomenine pretreatment significantly lowered ALT and AST, MDA, IL-6, apoptosis intensity, and TNF-α and restored mitochondrial biogenesis besides enhancement of SOD, sirtuin-1, and AMPK. Sinomenine also conferred hepatoprotective impact, as was apparent by lower pathologic changes. These effects were accompanied by changes in gene expression for AMPK/sirtuin-1/PGC-1α/PPARγ. The current study showed sinomenine hepatoprotective impact in CCl4-induced ALI that is associated with its regulation of mitochondrial biogenesis and parallel enhancement of AMPK/sirtuin-1.

New pressure-assisted sweeping on-line preconcentration for polar environmentally relevant nitrosamines: Part 1. sweeping for polar compounds and application of auxiliary pressure.

Typically sweeping reversed migration EKC (RM-EKC) is used for online enrichment and separation of neutral compounds in CE, however sweeping is not usually suitable for highly polar neutral compounds due to the lack of strong interaction with micellar phase. Since acidic BGE or coated capillaries (BGE pH 2-8) are used to virtually eliminate the EOF, migration of neutral analytes is only through association with the micelles with relatively slow electrophoretic mobility. To decrease the long analysis times that result, an auxiliary pressure can be applied, which also serves to avoid the associated band broadening. In this study, we have modified a commercially available CE instrument to perform pressure-assisted sweeping. The apparatus described can be used to precisely control the application of pressure, and therefore direction and magnitude of bulk flow in the capillary. This modification allows us to employ longer capillaries and capillaries with larger internal diameter to increase the sensitivity. An optimized method was used for the analysis of a group of seven N-nitrosamines that have been widely reported in environmental samples and good concentration factors of up to 34 were achieved. When a coated capillary is employed, this method is effective even at neutral pH, making it broadly applicable.

Therapeutic Potential of Isorhamnetin following Acetaminophen-Induced Hepatotoxicity through Targeting NLRP3/NF-κB/Nrf2.

Acetaminophen (APAP)-induced acute liver injury (ALI) is the principal cause of acute liver failure (ALF) in some countries including the United States and with few available treatments. Isorhamnetin is a bioflavonoid that is found in medicinal plants like Hippophae rhamnoides L. and Ginkgo biloba L. with promising potential to regulate inflammatory responses. In this study, we evaluated the possible effect of isorhamnetin in prevention of APAP-induced ALI and analyzed further the involvement of oxidative stress and inflammation-associated factors. Male C57BL/6 mice were given isorhamnetin (25 or 100 mg/kg b.w., p.o.) three times at 48, 24, and 1 h before APAP administration (300 mg/kg b.w., i.p.). Functional indicators of liver injury were measured as well as analysis of oxidative stress- and inflammation-associated indices and liver histopathology was also conducted. Isorhamnetin at the higher dose of 100 mg/kg significantly lowered serum levels of ALT, ALP, and AST in addition to reduction of ROS, TBARS, IL-6, TNFα, NF-kB, NLRP3, caspase 1, and MPO and significantly prevented reduction of GSH, SOD activity, sirtuin 1, and Nrf2. Additionally, isorhamnetin alleviated pathological changes of the liver tissue and suitably reversed NF-kB and Nrf2 immunoreactivity. These findings show protective effect of isorhamnetin against acetaminophen-induced liver injury through reducing oxidative stress, inflammation, and pyroptosis which is attributed to its regulation of NF-kB, Nrf2, NLRP3, and sirtuin 1.

High throughput direct analysis of water using solvothermal headspace desorption with porous thin films.

Sample preparation has remained a bottleneck in analysis of biological and environmental samples. Thus, microextraction techniques to reduce time, cost, labor, and environmental impacts as compared to traditional solid phase or liquid-liquid extractions are appealing. In this work, a high throughput extraction method coupled with a novel desorption technique has been developed for the analysis of eight regulated PAHs in water. The targeted analytes were extracted by thin film microextraction (TFME) using single-use sorbents. The enriched analytes on thin films were directly introduced into a gas chromatography with a flame ionization detector (GC-FID) through solvothermal headspace desorption (ST-HD). The desorption of analytes was accelerated by adding a small volume of solvent into the headspace vial. The parameters that influence desorption, such as type and volume of solvent, oven temperature, and desorption time, were studied. As well, the key parameters (stirring rate, extraction time, and salt content) for TFME of PAHs from water were assessed and optimized. Reusability and durability of the film and background noise due to polymer decomposition were also assessed. The method was validated using standards in 3.5% aqueous NaCl. The limits of detection (LODs) were between 0.2 and 2.0 ng mL-1, with linear ranges of 0.4-200.0 ng mL-1 with R2 > 0.99, and satisfactory accuracy and repeatability at three concentrations (low, mid, and high) within the linear range of the calibration curves. The calibration curves were also assessed for suitability as a matched matrix in the analysis of PAHs in a seawater sample. The technique was also applied for determination of PAHs in a produced water sample without the need for pretreatment and filtration of the sample. Although the complexity of produced water required the use of standard addition, we demonstrated that this approach is a useful tool for the analysis of complicated environmental samples.

A review on potential roles of vitamins in incidence, progression, and improvement of multiple sclerosis.

Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disease, with unknown etiology. Vitamins, as important micronutrients playing different roles in body, seem to be important in MS pathogenesis. In vitro, in vivo and human studies, supports the protective role of some vitamins in MS occurrence or progression. Current study reviews recent insights and reports about the importance of vitamins in MS incidence or progression. In accordance, the importance of all water and fat-soluble vitamins in MS pathogenesis based on observational studies in human population and their role in the function of immune system as well as possible therapeutic opportunities are discussed in depth throughout this review.