This study aimed to evaluate the protective action of oregano (
) essential oil and its monoterpene constituents (thymol and carvacrol) in L-arginine-induced kidney damage by studying inflammatory ...and tissue damage parameters. The determination of biochemical markers that reflect kidney function, i.e., serum levels of urea and creatinine, tissue levels of neutrophil-gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1), as well as a panel of oxidative-stress-related and inflammatory biomarkers, was performed. Furthermore, histopathological and immunohistochemical analyses of kidneys obtained from different experimental groups were conducted. Pre-treatment with the investigated compounds prevented an L-arginine-induced increase in serum and tissue kidney damage markers and, additionally, decreased the levels of inflammation-related parameters (TNF-α and nitric oxide concentrations and myeloperoxidase activity). Micromorphological kidney tissue changes correlate with the alterations observed in the biochemical parameters, as well as the expression of CD95 in tubule cells and CD68 in inflammatory infiltrate cells. The present results revealed that oregano essential oil, thymol, and carvacrol exert nephroprotective activity, which could be, to a great extent, associated with their anti-inflammatory, antiradical scavenging, and antiapoptotic action and, above all, due to their ability to lessen the disturbances arising from acute pancreatic damage. Further in-depth studies are needed in order to provide more detailed explanations of the observed activities.
Melatonin (MLT), earlier described as an effective anti-inflammatory agent, could be a beneficial adjunctive drug for sepsis treatment. This study aimed to determine the effects of MLT application in ...lipopolysaccharide (LPS)-induced sepsis in Wistar rats by determining the levels of liver tissue pro-inflammatory cytokines (TNF-α, IL-6) and NF-κB as well as hematological parameters indicating the state of sepsis. Additionally, an immunohistological analysis of CD14 molecule expression was conducted. Our research demonstrated that treatment with MLT prevented an LPS-induced increase in pro-inflammatory cytokines TNF-α and IL-6 and NF-κB levels, and in the neutrophil to lymphocyte ratio (NLR). On the other hand, MLT prevented a decrease in the blood lymphocyte number induced by LPS administration. Also, treatment with MLT decreased the liver tissue expression of the CD14 molecule observed after sepsis induction. In summary, in rats with LPS-induced sepsis, MLT was shown to be a significant anti-inflammatory agent with the potential to change the liver's immunological marker expression, thus ameliorating liver function.
The present study aimed to evaluate the protective action of thymol towards l-arginine-induced acute pancreatitis (AP) by studying the function of rat peritoneal immune cells.
Rat peritoneal exudate ...cells (PECs), obtained 24 h after the injection of l-arginine (350 mg/100 g of b.w.), were evaluated for mitochondrial activity (MTT assay), adherence capacity (methylene-blue assay), and phagocyte enzyme activity (myeloperoxidase, MPO, assay). The activity of α-amylase and free MPO, as well as the concentration of reactive oxygen species (ROS, i.e. O2−), were determined in the peritoneal exudate fluid. Also, serum α-amylase activity determination and pancreatic tissue pathohistological analysis were performed.
The administered thymol (50 and 100 mg/kg, per os) caused a significant decrease in the PEC mitochondrial activity and adherence capacity when compared with these functions of PECs isolated from rats with AP. A decrease in cellular MPO activity, as well as in the levels of ROS, α-amylase, and free MPO in peritoneal exudates was found in animals treated with thymol compared to the control animals with AP. Additionally, thymol administration prevented an increase in serum α-amylase activity, accompanied by the decrease in pancreatic tissue damage that follows l-arginine application.
The present results showed that thymol exerts significant immunomodulatory properties and a potential to silence PEC functions in inflammatory conditions such as the AP induced by l-arginine.
To complement the knowledge on the anti‐inflammatory activity of methyl and isopropyl N‐methylanthranilates, two natural products with panacea‐like properties, we investigated their effects on ...thioglycolate‐elicited macrophages by evaluating macrophage ability to metabolize MTT, macrophage membrane function, and macrophage myeloperoxidase and phagocytic activities. Moreover, two additional aspects of the inflammatory response of these compounds, their inhibitory activity on xanthine oxidase and catalase, were studied. It was found that these two compounds regulate elicited macrophage functions, most probably by interfering with the function of cell membranes and changing the reducing cellular capacity or enzyme activity of macrophages. Nonetheless, no significant inhibitory action either towards xanthine oxidase or catalase was found, suggesting that the inhibition of these enzymes is not involved in the anti‐inflammatory mode of action of these two esters.
Objective
The present study aimed to investigate the metabolic activity and adherence capacity of the whole bone marrow cell (wBMC) population and changes in bone marrow (BM) architecture after acute ...pancreatitis (AP) induction.
Methods
The disease was induced by injecting L-arginine (350 mg/100 g; i.p.). The control animals, animals injected with L-arginine, and animals pre-treated with allopurinol were included in this study. Serum and routine pathohistological analysis were conducted to confirm the induction of AP. The metabolic activity and adherence capacity of wBMC were evaluated in the MTT assay and methylene-blue test, respectively, and the alterations in pancreatic tissue and BM were examined on histological sections. In addition, immunohistochemical expression of β-catenin was assessed in the pancreatic tissue.
Results
The wBMC adherence capacity and their total number significantly increased after AP induction. The adherence capability of wBMC was reduced in rats pre-treated with allopurinol. There were no statistically significant changes in the metabolic activity of wBMCs. In the BM isolated from AP and allopurinol pre-treated animals, a discrete left shift in granulocytopoiesis was found, with a slight increase in the myeloid-to-erythroid ratio.
Conclusions
After AP induction, it was shown that wBMCs expressed increased adherence capacity and unchanged metabolic activity, while the alterations in BM may reflect the general activation of myelopoiesis, which would agree with the increased mobilization of mesenchymal stem cells. Also, a significant decrease in β-catenin expression in the pancreatic tissue was noticed.
Two new natural products, alpha -furanopinguisanol (1) and furanopinguisanone (2), were identified in the liverwort Porella cordaeana(Porellaceae). Although alpha -furanopinguisanol was previously ...reported in the literature, herein, we present arguments that its structure was actually erroneously assigned to a different, related compound. Structure elucidation was accomplished by spectral means (various 1D and 2D NMR experiments, IR, UV, MS) and the structures corroborated by chemical transformations. The relative configuration of the compounds was additionally verified by an analysis of shift changes produced by a lanthanide shift reagent. Immunomodulatory properties of these two compounds were also investigated. Their influence on rat splenocytes (SPCs) was monitored through MTT, trypan blue and neutral red assays, microscopic investigation of cells, comet assay, and protein, RNA and DNA contents. It was shown that, in higher concentration (10 super(-4) M), compound 1 induced a blast-like transformation of SPCs, while in lower ones (10 super(-8) to 10 super(-6) M) it acted as a cytotoxic agent. On the other hand, compound 2 exerted prominent cytotoxicity in all concentrations. It the light of the obtained data, a possible mechanism of action of the two compounds was discussed.
Previously 3 sesquiterpenoids from Conocephalum conicum (L.) Dum. (Conocephalaceae) were found to modulate lymphocyte response to different stimuli, suggesting their immunomodulatory potential. ...Herein we evaluated the impact of low concentrations of these sesquiterpenoids on rat splenocyte viability and membrane permeability, as well as lactate dehydrogenase (LDH) activity, in order to, possibly, shed light on their mechanism of action. After a 24 h incubation of splenocytes with the sesquiterpenoids (from 10−8 to 10−6 M), MTT and trypan blue (TB) assays, as well as histochemical staining for LDH, were performed. The tested compounds were shown not to reduce the ability of cells to metabolize MTT; however, cell membrane permeability to TB was altered, suggesting that a certain percentage of cells were dead. Histochemical staining for LDH presence releveled that only 2, out of the 3 sesquiterpenoids, decreased the staining intensity, indicating either LDH leakage or its inhibition. In conclusion, having in mind the already proven modulatory potential of the tested sesquiterpenoids, the present results suggest that through the changes in the cell membrane function and leakage/inhibition of LDH in unaltered immune cells, some of the tested compounds could be considered promising candidates for further research as anticancer agents.
Immunomodulatory and antimicrobial activities of six gold(III) complexes and the corresponding N-donor ligands differing in denticity were assessed. Among the complexes, fully structurally and ...spectrally characterized, 1c caused the highest decrease in macrophage and splenocyte viability. 1c displayed excellent activity in both pre- and post-adhesion phases of Pseudomonas aeruginosa-biofilm formation.
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Six gold(III) complexes with ligands of differing denticity, HGly-Met sulfoxideAuCl4 (1b), Au(en)Cl2Cl·2H2O (1c), Au(dien)ClCl2 (1d), Au(Gly-l-His)ClNO3·1.25H2O (1e), Au(l-Ala-l-His)ClNO3·2.5H2O (1f) and Au(Gly-Gly-l-His)Cl·H2O (1g), were synthesized and structurally characterized. These complexes, along with the starting compounds used for their synthesis, were tested for their immunomodulatory and antimicrobial activities. Immunomodulation was investigated by assessing their cytotoxicity towards mouse spleen lymphocytes and peritoneal macrophages. Their antimicrobial effect was tested against a panel of Gram-positive and Gram-negative bacterial strains including ATCC strains and resistant isolates. Antimicrobial potential of 1b-g was further explored by evaluating their antibiofilm activity against biofilm-forming Pseudomonas aeruginosa. All gold(III) complexes inhibited biofilm production of P. aeruginosa strains, where ethylenediamine-containing gold(III) complex 1c exhibited the strongest reduction of biofilms superseding the activity of the used antibiotic, leaving only 10% of biofilm unaffected. All investigated gold(III) complexes inhibited biofilm formation after 72 h of incubation, showing long-term effectiveness, which was visualized by microscopy during this time. The mode of antibiofilm action was evaluated by testing the effect of this complex on P. aeruginosa motility forms. Among the all investigated compounds, 1c possesses the highest both cytotoxic and antimicrobial action, making this complex a good candidate for further pharmacological evaluations.
Two new ferrocene–indole hybrids were designed, synthesized and characterized by extensive 2D NMR studies. Although the compounds exerted weak inhibition of acetylcholinesterase, they demonstrated ...significant cytotoxic activities against Artemia salina (24h LD50 20.7 and 120.4μM) and rat macrophages (IC50 ca. 0.5μM for both compounds). Display omitted
Incorporation of a ferrocene moiety into the 2-phenylindole scaffold has been recently reported to drastically improve the cytotoxic activity of the parent compounds. In our search for new promising cytotoxic agents we designed and prepared two new ferrocene–indole hybrids, 2-(3-ferrocenylphenyl)-1H-indole and 2-(4-ferrocenylphenyl)-1H-indole, utilizing the Fischer indole synthesis as the key step. Detailed spectral analyses, including 1D and 2D NMR in various solvents, have been carried out to corroborate the structures of the synthesized compounds. In this work, we also present the first results of biological studies of these two compounds. Both compounds showed weak anticholinesterase activity but high cytotoxicity against rat peritoneal macrophages and the crustacean Artemia salina. Also, both compounds showed significant myeloperoxidase inhibiting activity, thus suggesting a potential use in inflammatory disorders. The results of these tests are very encouraging as they also suggest possible cytotoxic activities of these compounds against human cancer cell lines.
Two new Zn(II) complexes with tridentate hydrazone-based ligands (condensation products of 2-acetylthiazole) were synthesized and characterized by infrared (IR) and nuclear magnetic resonance (NMR) ...spectroscopy and single crystal X-ray diffraction methods. The complexes
,
and recently synthesized Zn
(NCS)
(
= (
)-
,
,
-trimethyl-2-oxo-2-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)ethan-1-aminium) complex
were tested as potential catalysts for the ketone-amine-alkyne (KA
) coupling reaction. The gas-phase geometry optimization of newly synthesized and characterized Zn(II) complexes has been computed at the density functional theory (DFT)/B3LYP/6-31G level of theory, while the highest occupied molecular orbital and lowest unoccupied molecular orbital (HOMO and LUMO) energies were calculated within the time-dependent density functional theory (TD-DFT) at B3LYP/6-31G and B3LYP/6-311G(d,p) levels of theory. From the energies of frontier molecular orbitals (HOMO-LUMO), the reactivity descriptors, such as chemical potential (
), hardness (
), softness (
), electronegativity (
) and electrophilicity index (
) have been calculated. The energetic behavior of the investigated compounds (
and
) has been examined in gas phase and solvent media using the polarizable continuum model. For comparison reasons, the same calculations have been performed for recently synthesized Zn
(NCS)
complex
. DFT results show that compound
has the smaller frontier orbital gap so, it is more polarizable and is associated with a higher chemical reactivity, low kinetic stability and is termed as soft molecule.
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