Evaluation of genotoxic and mitotoxic effects of TAF-loaded chitosan nanoparticles in HepG2 cells.

Tenofovir alafenamide (TAF) is a new drug from the nucleotide reverse transcriptase inhibitor group approved for the treatment of chronic Hepatitis B in 2016. With this study, we aimed to test whether possible cellular toxicity can be reduced by controlled drug release as a result of loading with chitosan nanoparticles (CHS). We investigated the genotoxic and mitotoxic effects of 45 µM TAF-loaded CHS and TAF-only on HepG2 cells by micronucleus (MN), comet assay, determination of mtDNA quantification, mitochondrial membrane potential (ΔΨm), and ROS levels. Additionally, we compared the samples by RNAseq analyses to reveal the transcriptional responses to each regimen. In terms of genotoxic tests, although MN and comet were found higher in all experimental treatment conditions, the encapsulation of CHS reduced the genotoxicity of TAF. MtDNA level was found to be lower in the TAF treatment, whereas it was higher in CHS and CHS-TAF treatments. The TAF-loaded CHS and TAF treatments had an impaired ΔΨm value. Cellular ROS levels were higher in all treatment conditions. According to the analyses of gene expression patterns; CHS-only changed the expression of relatively few genes (187 genes), while TAF changed the expression of the 1974 genes and TAF-loaded CHS changed the expression of 734 genes. Considering the gene expression numbers, CHS encapsulation of TAF significantly reduced the number of genes that were differentially expressed by TAF-only. Overall, we observed that TAF has genotoxic and mitotoxic effects on HepG2 cells, and upon encapsulation with CHS, its genotoxic and mitotoxic effects were decreased.

Chemistry, Structures, and Advanced Applications of Nanocomposites from Biorenewable Resources.

Researchers have recently focused on the advancement of new materials from biorenewable and sustainable sources because of great concerns about the environment, waste accumulation and destruction, and the inevitable depletion of fossil resources. Biorenewable materials have been extensively used as a matrix or reinforcement in many applications. In the development of innovative methods and materials, composites offer important advantages because of their excellent properties such as ease of fabrication, higher mechanical properties, high thermal stability, and many more. Especially, nanocomposites (obtained by using biorenewable sources) have significant advantages when compared to conventional composites. Nanocomposites have been utilized in many applications including food, biomedical, electroanalysis, energy storage, wastewater treatment, automotive, etc. This comprehensive review provides chemistry, structures, advanced applications, and recent developments about nanocomposites obtained from biorenewable sources.

Novel hybrid isoindole-1,3(2H)-dione compounds containing a 1H-tetrazole moiety: Synthesis, biological evaluation, and molecular docking studies.

In this study, novel hybrid isoindole-1,3(2H)-dione compounds (10 and 11) carrying a 1H-tetrazole moiety were synthesized, characterized and their inhibitory properties against xanthine oxidase (XO) and carbonic anhydrase isoenzymes (hCA I and hCA II) were investigated. Allopurinol for XO and acetazolamide for carbonic anhydrase isoenzymes were used as positive standards in inhibition studies. In addition, compounds 8 and 9, which were obtained in the intermediate step, were also investigated for their inhibition effects against the three enzymes. According to the enzyme inhibition results, hybrid isoindole-1,3(2H)-dione derivatives 10 and 11 showed significant inhibitory effects against all three enzymes. Surprisingly, compound 8, containing a SCN functional group, exhibited a greater inhibitory effect than the other compounds against hCA I and hCA II. The IC50 values of compound 8 against hCA I and hCA II were found to be 3.698 ± 0.079 and 3.147 ± 0.083 µM, respectively. Compound 8 (IC50 = 4.261 ± 0.034 µM) showed higher activity than allopurinol (IC50 = 4.678 ± 0.029 µM) and the other compounds against XO, as well. These results clearly show the effect of the SCN group on the inhibition. In addition, in silico molecular docking studies were performed to understand the molecular interactions between each compound and enzymes, and the results were evaluated.

Synthesis, inhibition properties against xanthine oxidase and molecular docking studies of dimethyl N-benzyl-1H-1,2,3-triazole-4,5-dicarboxylate and (N-benzyl-1H-1,2,3-triazole-4,5-diyl)dimethanol derivatives.

This study focused on synthesis various dimethyl N-benzyl-1H-1,2,3-triazole-4,5-dicarboxylate and (N-benzyl-1H-1,2,3-triazole-4,5-diyl)dimethanol derivatives under the conditions of green chemistry without the use of solvent and catalysts. Their inhibition properties were also investigated on xanthine oxidase (XO) activity. All dimethanol and dicarboxylate derivatives exhibited significant inhibition activities with IC50 values ranging from 0.71 to 2.25 µM. Especially, (1-(3-bromobenzyl)-1H-1,2,3-triazole-4,5-diyl)dimethanol (5c) and dimethyl 1-(4-chlorobenzyl)-1H-1,2,3-triazole-4,5-dicarboxylate (6 g) compounds were found to be the most promising derivatives on the XO enzyme inhibition with IC50 values 0.71 and 0.73 µM, respectively. Moreover, the double docking procedure was to evaluate compound modes of inhibition and their interactions with the protein (XO) at atomic level. Surprisingly, the docking results showed a good correlation with IC50 [correlation coefficient (R2 = 0.7455)]. Also, the docking results exhibited that the 5c, 6f and 6 g have lowest docking scores -4.790, -4.755, and -4.730, respectively. These data were in agreement with the IC50 values. These results give promising beginning stages to assist in the improvement of novel and powerful inhibitor against XO.

Therapeutic potential of coumarin bearing metal complexes: Where are we headed?

The successfully application of some metallodrugs such as salvarsan, silver sulfadiazine and cisplatin in modern medicine launched the biological investigation of organometallic and metal-organic complexes. The availability and tunability of various ligands including N-heterocycles, phosphines, N-heterocyclic carbenes present an extended research area to chemists. In recent years, the preparation of the metal complexes of bioactive organic compounds is a new strategy. Coumarin derivatives are one of the classes of compounds used for this purpose, and many complexes of coumarin derivatives were prepared for enhanced biological activity, especially anticancer and antimicrobial. In this paper, we discuss the current situation of this topic.

Chemistry, structure, and biological roles of Au-NHC complexes as TrxR inhibitors.

In recent years, the preparation of metal complexes and the introduction of biologically active organometalic compounds are new strategies in drug development. For this purpose, generally N-heterocyclic pharmaceutical agents have been used as promising nuclei. Au-containing N-heterocyclic carbene (Au-NHC) derivatives are among the compounds used for this purpose, and their enzyme inhibition, antioxidant activity, antimicrobial and anticancer properties are widely studied. In these studies, the anticancer property of Au-NHC complexes is the most widely studied area. The common result in different studies has been revealed that mitochondrial thioredoxin reductases (TrxR) inhibition is the main pathway in the powerful anticancer effect of many Au-NHC complexes. In TrxR inhibition, the high affinity of gold to sulfur is considered to be the main component of the effect. This review includes the discussions releated to the anticancer activities and TrxR inhibition properties of Au-NHC compounds.

Water Soluble Coumarin Quaternary Ammonium Chlorides: Synthesis and Biological Evaluation.

In the present study, coumarin-bearing three pyridinium and three tetra-alkyl ammonium salts were synthesized. The compounds were fully characterized by 1 H- and 13 C-NMR, LC/MS and IR spectroscopic methods and elemental analyses. The cytotoxic properties of all compounds were tested against human liver cancer (HepG2), human colorectal cancer (Caco-2) and non-cancer mouse fibroblast (L-929) cell lines. Some compounds performed comparable cytotoxicity with standard drug cisplatin. Antibacterial properties of the compounds were tested against Gram-negative Escherichia coli and Gram-positive Bacillus subtilis bacteria, but the compounds did not have any antibacterial effect against both bacteria. Enzyme inhibitory properties of all compounds were tested on the activities of human carbonic anhydrase I and II, and xanthine oxidase. All compounds inhibited both enzymes more effectively than standard drugs, acetazolamide and allopurinol, respectively. The biological evaluation results showed that ionic and water soluble coumarin derivatives are promising structures for further investigations especially on enzyme inhibition field.

Synthesis, biological evaluation and molecular docking studies of bis-chalcone derivatives as xanthine oxidase inhibitors and anticancer agents.

In this study, a series of B-ring fluoro substituted bis-chalcone derivatives were synthesized by Claisen-Schmidt condensation reactions and evaluated for their ability to inhibit xanthine oxidase (XO) and growth inhibitory activity against MCF-7 and Caco-2 human cancer cell lines, in vitro. According to the results obtained, the bis-chalcone with fluoro group at the 2 (4b) or 2,5-position (4g) of B-ring were found to be potent inhibitors of the enzyme with IC50 values in the low micromolar range. The effects of these compounds were about 7 fold higher than allopurinol. The binding modes of the bis-chalcone derivatives in the active site of xanthine oxidase were explained using molecular docking calculations. Also, compound 4g and 4h showed in vitro growth inhibitory activity against a panel of two human cancer cell lines 1.9 and 6.8 µM of IC50 values, respectively.

New morpholine-liganded palladium(II) N-heterocyclic carbene complexes: Synthesis, characterization, crystal structure, and DNA-binding studies.

A series of the morpholine-liganded palladium(II) complexes (1a-e) bearing N-heterocyclic carbene (NHC) functionalized by benzonitrile were synthesized. These complexes were synthesized from (NHC)Pd(II)(pyridine) complexes (PEPPSI) and morpholine. The new complexes were fully characterized by using 1 H NMR, 13 C NMR, Fourier-transform infrared spectroscopy, and elemental analysis techniques. Single-crystal X-ray diffraction was used to determine the structure of a derivative. The DNA-binding studies of the new (NHC)Pd(II)morpholine complexes were examined using the pBR322 plasmid. The 2,4,6-trimethylbenzyl derivative compound has the most DNA binding activity. In addition, for the 3-methylbenzyl derivative compound, oxidation effects were observed at concentrations higher than 100 µg/ml. Also, the molecular and crystal structures of the complex 3-methylbenzyl derivative compound were recorded by using a single-crystal X-ray diffraction method.

Protective effects of ghrelin on kidney tissue in rats with partial ureteral obstruction

Background/aim: The aim was to investigate the protective and therapeutic effects of ghrelin, which has antioxidant and antiinflammatory activity, on preventing kidney damage that occurs by induced partial ureteral obstruction in rats Materials and methods: Twenty-eight adult male rats were included in the study, and the rats were divided into 4 groups. After the laparotomy operation on the sham group, the ureter was identified in the retroperitoneal area and was duly sutured (n = 7). Ghrelin was administered for seven days intraperitoneally, and after the nephrectomy performed on the 15th day, the rats were sacrificed (n = 7). A partial ureteral obstruction was performed after the laparotomy on the PUO group. The rats were sacrificed after the nephrectomy operation performed on the 15th day (n = 7). A partial ureteral obstruction was formed after the laparotomy followed by seven days of waiting in the PUO + ghrelin group. Ghrelin was given in the dose of 10 ng/kg per day intraperitoneally for the next 7 days, and the rats were sacrificed after the nephrectomy operation performed on the 15th day (n = 7). All groups were evaluated for histological damage and catalase, superoxide dismutase, total glutathione, malondialdehyde, and myeloperoxidase levels were measured in the same tissues Results: When the 2nd group and the sham group were compared histologically, it was observed that the damage had increased by a statistically significant level in the partial ureteral obstruction group (P = 0.001). When the group which was ghrelin-treated after the partial ureteral obstruction was compared to the group with just partial ureteral obstruction, the histopathological changes were found to decrease significantly in that group (P = 0.001). While the statistical significance of the levels of CAT, GSH, and MPO enzymes was detected among biochemical changes in the 2nd group when compared to the sham group (P < 0.01), the 3rd group showed a statistically significant difference in the levels of SOD and GSH enzymes compared to the 4th group (P < 0.05). Conclusion: Ghrelin administration to rats after the formation of an experimental partial unilateral ureteral obstruction reduces tissue damage due to ghrelin's antiinflammatory and antioxidant effects. Ghrelin administration may prevent tissue damage biochemically and histopathologically in obstructive uropathy cases

Xanthine oxidase inhibitory activity of new pyrrole carboxamide derivatives: In vitro and in silico studies.

Pyrrole carboxamide rings are rarely used as active scaffold in designing inhibitors for enzymes. Herein, we described the structure-activity relationship for novel xanthine oxidase inhibitors based on the pyrrole carboxamide scaffold. A series of novel-substituted pyrrole carboxamide derivatives were synthesized and characterized; their in vitro and in silico inhibitory activities were determined against xanthine oxidase. Among these compounds, those which contain no substituent and one methyl group at the para-position of the phenyl moiety in the main structure, respectively, were found out as most active according to the xanthine oxidase inhibition activity study. In silico techniques reveal why these compounds display more activities than others, based on their binding interactions with xanthine oxidase and the surface scanning results of the enzyme. Furthermore, the binding energy calculations displayed good agreement with the experimental activity values.

Immobilization of l-Asparaginase on Carrier Materials: A Comprehensive Review.

There are two major applications of l-asparaginase (L-ASNase): leukemia therapy and the food industry. Especially, its chemotherapeutic effect has attracted interest from the scientific community and individual scientists. Therefore, to protect the intrinsic activity and half-time of L-ASNase, several carriers and immobilization techniques for immobilization of L-ASNase have been described in articles. Unfortunately, a comprehensive review about immobilization of L-ASNase has not been written until now. In this review, we have thoroughly discussed the carriers for L-ASNase by illustrating immobilization findings including both past and present applications. In addition, we have revealed advantages and disadvantages of immobilized enzyme and related it to free form. We believe that this review will not only provide background information, but also guide future developments.

Synthesis, antioxidant and anti-microbial properties of two organoselenium compounds.

The aim of this study is synthesis of two different series of organoselenium compounds and available in vitro antioxidant and antimicrobial properties of these synthetic compounds. The synthetic compounds were identified by (1)H-NMR (300 MHz), (13)C-NMR (75.5 MHz), FT-IR spectroscopic techniques and micro analysis. Antioxidant properties of two synthetic organoselenium compounds were determined by 1,1- diphenyl-2-picrylhydrazyl (DPPH) radical method, reducing power assay and ß-carotene bleaching method as in vitro. Antimicrobial effects of samples were assessed by the agar dilution procedure and using gram positive and gram-negative bacteria and yeast strains. Although 1,3-di-p-methoxybenzylpyrimidine-2-selenone showed better antiradical activity in DPPH test and higher protective activity on ß-carotene, 1-isopropyl-3-methylbenzimidazole-2-selenone was found to be better in reducing power and antimicrobial activity.

Protective effects of melatonin and quercetin on experimental lung injury induced by carbon tetrachloride in rats.

INTRODUCTION: Exposure to carbon tetrachloride (CCl4), a well-known toxicant, causes tissue damage by inducing oxidative stress via formation of free radicals. The fundamental structure of the organs of rats and humans is similar, so administration of CCl4 to rats is an accepted experimental model to produce oxidative damage to various tissues including pulmonary tissue. In this study, we evaluated the protective capacity of melatonin and quercetin against CCl4-induced oxidative lung damage in rats. MATERIAL-METHODS: Rats were divided into five groups each containing seven rats as follows: Control group, Olive oil group CCl4 group, CCl4+Melatonin, and CCl4+Quercetin group. The tissue samples were processed by routine histological and biochemical procedures. Sections were stained with Hematoxylin-eosin and Masson's trichrome. Histopathologic damage score was calculated. Malondialdehyde (MDA) and glutathione (GSH) levels and catalase (CAT) activities were assayed. RESULTS: The lung sections of control groups showed normal histological characteristics. Fibrosis, interstitial hemorrhage, epithelial desquamation in bronchiole and alveoli, intra-alveolar edema, leukocyte, and macrophage infiltration were observed in lung sections of rats exposed to CCl4 alone. The findings were reduced in the treatments groups. The MDA level in the CCI4 group were significantly higher than in the other groups (p < .001), and the CAT and GSH levels in the CCI4+Mel and CCI4+Quer groups were significantly higher than in the CCI4 group (p < .05). CONCLUSION: In conclusion, we suggest that agents with antioxidant properties such as melatonin and quercetin may have positive effects in the treatment of pulmonary diseases characterized by especially edema, inflammation, and fibrosis.

Horseradish Peroxidase Immobilized onto Mesoporous Magnetic Hybrid Nanoflowers for Enzymatic Decolorization of Textile Dyes: A Highly Robust Bioreactor and Boosted Enzyme Stability.

Recently, hybrid nanoflowers (hNFs), which are accepted as popular carrier supports in the development of enzyme immobilization strategies, have attracted much attention. In this study, the horseradish peroxidase (HRP) was immobilized to mesoporous magnetic Fe3O4-NH2 by forming Schiff base compounds and the HRP@Fe3O4-NH2/hNFs were then synthesized. Under optimal conditions, 95.0% of the available HRP was immobilized on the Fe3O4-NH2/hNFs. Structural morphology and characterization of synthesized HRP@Fe3O4-NH2/hNFs were investigated. The results demonstrated that the average size of HRP@Fe3O4-NH2/hNFs was determined to be around 220 nm. The ζ-potential and magnetic saturation values of HRP@Fe3O4-NH2/hNFs were -33.58 mV and ∼30 emu/g, respectively. Additionally, the optimum pH, optimum temperature, thermal stability, kinetic parameters, reusability, and storage stability were examined. It was observed that the optimum pH value shifted from 5.0 to pH 8.0 after immobilization, while the optimum temperature shifted from 30 to 80 °C. K m values were calculated to be 15.5502 and 7.6707 mM for free HRP and the HRP@Fe3O4-NH2/hNFs, respectively, and V max values were calculated to be 0.0701 and 0.0038 mM min-1. The low K m value observed after immobilization indicated that the affinity of HRP for its substrate increased. The HRP@Fe3O4-NH2/hNFs showed higher thermal stability than free HRP, and its residual activity after six usage cycles was approximately 45%. While free HRP lost all of its activity within 120 min at 65 °C, the HRP@Fe3O4-NH2/hNFs retained almost all of its activity during the 6 h incubation period at 80 °C. Most importantly, the HRP@Fe3O4-NH2/hNFs demonstrated good potential efficiency for the biodegradation of methyl orange, phenol red, and methylene blue dyes. The HRP@Fe3O4-NH2/hNFs were used for a total of 8 cycles to degrade methyl orange, phenol red, and methylene blue, and degradation of around 81, 96, and 56% was obtained in 8 h, respectively. Overall, we believe that the HRP@Fe3O4-NH2/hNFs reported in this work can be potentially used in various industrial and environmental applications, particularly for the biodegradation of recalcitrant compounds, such as textile dyes.

Unveiling the effect of molecular weight of vanillic acid grafted chitosan hydrogel films on physical, antioxidant, and antimicrobial properties for application in food packaging.

Till now, a wide range of chitosan (CHS)-based food packaging films have been developed. Yet, the role of molecular weight (MW), which is an important physical property of CHS, in determining the physicochemical and biochemical properties of vanillic acid (VA)-grafted CHS hydrogel films synthesized using CHS with different MWs has not been investigated until now. Three kinds of CHS including low, medium, and high MWs were grafted separately with VA through a carbodiimide mediated coupling reaction. No significant difference in water resistance properties was observed with increasing MW of CHS, in contrast to obvious decrease in light transmittance and opacity. The VA-g-CHS hydrogel films exhibited significantly improved light blocking capacity. A significant improvement in antioxidant (~6-fold) and antimicrobial (~1.2-fold) activity was observed after grafting with VA. In contrast, the free radical scavenging and antimicrobial activity decreased with increasing MW of CHS. Most importantly, VA-g-CHS hydrogel films could maintain the freshness of cherry tomatoes for up to 10 days at ~25 °C. However, no significant difference was observed depending on the MW value of CHS. This pioneering work is of great importance in guiding the selection of MW of CHS biomacromolecule to design hydrogel films with desired physicochemical and biochemical properties.

Enhancement of enzyme activity by laser-induced energy propulsion of upconverting nanoparticles under near-infrared light: A comprehensive methodology for in vitro and in vivo applications.

If the appropriate immobilization method and carrier support are not selected, partial decreases in the activity of enzymes may occur after immobilization. Herein, to overcome this challenge, an excitation mechanism that enables energy transfer was proposed. Modified upconverting nanoparticles (UCNPs) were constructed and the important role of near-infrared (NIR) excitation in enhancing the catalytic activity of the enzyme was demonstrated. For this purpose, UCNPs were first synthesized via the hydrothermal method, functionalized with isocyanate groups, and then, PEG-L-ASNase was immobilized via covalent binding. UCNPs with and without PEG-L-ASNase were extensively characterized by different methods. These supports had immobilization yield and activity efficiency of >96 % and 78 %, respectively. Moreover, immobilized enzymes exhibited improved pH, thermal, and storage stability. In addition, they retained >65 % of their initial activity even after 20 catalytic cycles. Biochemical and histological findings did not indicate a trend of toxicity in rats due to UCNPs. Most importantly, PEG-L-ASNase activity was triggered approximately 5- and 2-fold under in vitro and in vivo conditions, respectively. Overall, it is anticipated that this pioneering work will shed new light on the realistic and promising usage of NIR-excited UCNPs for the immobilization of enzymes in expensive and extensive applications.

Effects of ozone therapy on cyclophosphamide-induced urinary bladder toxicity in rats.

PURPOSE: This study investigated the efficacy of ozone therapy (OT) in a rat model of cyclophosphamide-induced hemorrhagic cystitis (HC). METHODS: Forty Wistar Albino male rats were divided into five groups: sham, OT, cyclophosphamide (CP), OT+CP and CP+OT. Hemorrhagic cystitis (HC) was induced by intraperitoneal (i.p) administration a single dose of 100 mg/kg CP. OT was performed once daily for three days. The CP+OT group received OT (0.2 mg/kg) i.p 24 h after CP administration. CP was injected to the OT+CP group the day after the third course of OT. All animals were killed four days after CP administration. Bladder injury and oxidative stress parameters were determined from tissue samples. RESULTS: We found small, but non-statistically significant biochemical and histological changes in the animals treated with OT alone. CP administration induced cystitis, as manifested by a marked loss of urothelial cells, as well as hemorrhaging and edema in the bladder as determined by histopathological examination. It also caused a significant decrease in the endogenous antioxidant compound glutathione (GSH) and elevation of lipid peroxidation, and nitric oxide (NO) and myeloperoxidase (MPO) levels in the rats' urinary bladder tissue. OT was able to ameliorate these changes; however these effects were prominent in the CP+OT group when compared with the OT+CP group.: For example, the NO level in the CP+OT group was 68% of the OT+CP group (p < 0.05). CONCLUSION: OT prevented CP-induced urothelial damage by diminishing bladder oxidative stress, inflammation and NO levels. OT may help to ameliorate bladder damage induced by CP in the clinical setting.

Modulating effects of selenium in adrenal medulla of rats exposed to 7,12-dimethylbenz[a]anthracene.

OBJECTIVE: The aim of this study was to evaluate the chemopreventive potential of organoselenium compounds (Se I and Se II) in the well-established rat model treated with 7,12-dimethylbenz[a]anthracene (DMBA), by monitoring the extent of tyrosine hydroxylase (TH) activity, adrenomedullin (ADM) level and total RNA level in adrenal medulla. Organic pollutants are the most important environmental factor for the biologic systems. DMBA exposure appears to be associated with a number of physiological disease processes. METHODS: The effects of Se I and Se II compounds were investigated on TH activity, ADM and total RNA levels in adrenal medulla of rats exposed to DMBA. RESULTS: TH activity, ADM and total RNA levels were found to be increased significantly due to the effect of DMBA (p < 0.05). This increase was restricted in the Se I- and Se II-treated groups (p < 0.05). CONCLUSION: The present data showed that the organoselenium compounds may have important effects in the maintainance of homeostasis against stress induced by DMBA.

The effects of pentoxifylline and caffeic acid phenethyl ester on TNF-α and lung histopathology in D-galactosamine-induced pulmonary injury in rats.

In this study, we aimed to investigate the effects of pentoxifylline [PTX] and caffeic acid phenethyl ester [CAPE] in D-galactosamine [D-GAL]-induced pulmonary injury in rats. The rats were randomly divided into six groups: control, D-GAL, D-GAL+PTX, D-GAL+CAPE, PTX and CAPE. Each group included eight animals. Lung sections from the control, PTX and CAPE groups had a normal histological appearance. The D-GAL group showed histopathological changes in lung tissue, including haemorrhage, oedema, inter-alveolar septal thickening and widespread infiltration of inflammatory lymphocytes and macrophages. Administration of PTX and CAPE significantly reduced histopathological damage scores in the D-GAL+PTX and D-GAL+CAPE groups compared with the D-GAL group. PTX and CAPE treatment also significantly decreased malondialdehyde levels, increased levels of reduced GSH and increased catalase and superoxide dismutase activity in lung tissue samples. These results indicate that the destructive effects of D-GAL-induced inflammation in the rat lung are significantly reduced following administration of PTX and CAPE.