Protective Effect of Tunisian Flaxseed Oil against Bleomycin-Induced Pulmonary Fibrosis in Rats.

The aims of this study are to investigate the preventive effect of flaxseed oil (FO) on bleomycin (BLM)-induced pulmonary fibrosis (PF). Thirty adult male Wistar rats (180-220 g) were randomly divided into three groups. The control group (G1) received no treatment, the group (G2) received only intratracheally BLM, and the group (G3) received FO (2 mL/kg body weight) once a day for 60 days + BLM (4 mg/kg body weight "bw"). Our results demonstrated that FO protected against BLM-induced PF, by increasing proline, fructose, glucose, glyceride, choline, lactate, and malate metabolites in bronchoalveolar lavage fluid (Balf) which are involved in anti-inflammatory reactions. Also, FO-treatment reduced the score of fibrosis and the inflammatory index and revealed a decrease in tumor growth factor beta (TGFß) density in alveoli, inflammatory infiltrate and fibrocytes, comparatively to the BLM group. As well, our data demonstrated that acute BLM-induced fibrosis was accompanied by an oxidative stress in lung tissue as assessed by an increase of lipid peroxidation as well as antioxidant enzyme activities depletion such as superoxide dismutase (SOD) and catalase (CAT). The FO treatment reversed all disturbances of BLM-induced oxidative stress parameters, and increased fatty acids levels promoting anti-inflammatory reactions especially in erythrocytes (linoleic, α-linolenic, docosapentaenoic acids).

A comparative study of intratracheal and aerosolization instillations of bleomycin inducing experimental lung fibrosis in rat.

We aimed to investigate in the present work, using metabonomics approaches, the scalability of lung fibrosis-biomarkers, in bleomycin (BLM) model of pulmonary fibrosis in rats. Sixty male Wistar rats, weighing 250 ± 10 g, were randomly divided into three groups: a negative control group receiving normal saline treatment (G1), an intratracheal BLM instilled group (G2), and an aerosol BLM instilled group (G3). Rats were investigated at various times after BLM instillation. Metabolic changes observed in different biofluids have been integrated into the results of the histological examination (increase in inflammation, fibrosis score, and TGF-ß immunostaining) which provide a novel pathway of biomarkers in pulmonary fibrosis. These two BLM-models showed an efficacy in the production of pulmonary fibrosis in rats, accompanied by an oxidative stress in lung tissue as assessed by the increase of lipid peroxidation and the depletion in the level of antioxidant enzymes such as superoxide dismutase and catalase. The aerosol model was more advantageous showing fibrotic foci occupying the majority of the lung in contrast to intratracheal instillation characterized by a non-homogeneous distribution of the fibroblastic foci.

Protective Effect of Pistacia lentiscus Oil Against Bleomycin-Induced Lung Fibrosis and Oxidative Stress in Rat.

We aimed in the present study to investigate the protective effect of Pistacia lentiscus oil against bleomycin-induced lung fibrosis as well as the involvement of oxidative stress in such protection. In this respect, adult male Wistar rats were used and divided into three groups of twenty each: control (NaCl, 0.9%), bleomycin, and bleomycin (4 mg/kg b.w.) + P. lentiscus oil (3 g/kg, b.w.). Animals were pretreated for 30 days before the induction of fibrosis by bleomycin and 1 wk after the induction of fibrosis. The oil principal compounds detected by gas chromatography analysis are: Linoleic and palmitic acids (70.6 and 24.7%, respectively). Our data demonstrated that P. lentiscus oil protected against bleomycin-induced fibrosis as evidenced by TGFß immunostaining increase in lungs fibrocytes as well as inflammatory infiltrate. We also showed that acute bleomycin-induced fibrosis was accompanied by an oxidative stress in lung tissue as assessed by an increase of lipid peroxidation as well as antioxidant enzyme activities depletion such as superoxide dismutase (SOD) and catalase (CAT). More importantly, P. lentiscus oil treatment reversed all bleomycin-induced oxidative stress parameters disturbances. In conclusion, we suggest that P. lentiscus oil had potent protective effects against bleomycin-induced fibrosis due in part to its antioxidant properties.

Effect of Pistacia lentiscus oil on experimental pulmonary fibrosis.

Background - Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by histopathological lesions in lung tissue. This is the most common and most severe idiopathic interstitial pneumonias. Current treatments are based on the combination of corticosteroids and immunosuppressants, but their effectiveness is still debated. Purpose of work - Testing the preventive effect of Pistacia Lentiscus oil, known for its antioxidant, anti-mutagenic and anti-proliferative effects, on a model of experimental lung fibrosis. Methods - Two groups of rats received an intratracheal injection of bleomycin (4.5 mg / kg). The first group, control (n = 20 rats), has received no treatment. The second group was treated with Pistacia Lentiscus oil (n = 20 rats) for 30 days before fibrosis induction, by daily gavage oil Pistacia Lentiscus oil (3,33ml / kg). This treatment was continued for 10 days. At the end of the experimental period, all rats were sacrificed and the lung tissue was examined histopathologically and immunostained for TGFß. Results - The chromatographic profile oil Pistacia Lentiscus oil shows the dominance of two fatty acids that are linoleic acid and palmitic acid representing respectively 70.57 and 24.67%. Our results also show a decrease in the distribution of TGFß both at the level of the inflammatory infiltrate and at the level of the pulmonary parenchyma histiocytes of rats treated with Pistacia Lentiscus oil compared with control rats. However, these changes are not accompanied by statistically significant changes of fibrosis score and inflammatory index. Conclusion - Our results are interesting to consider. Further studies using higher doses of Pistacia Lentiscus oil are important to conduct.

Structural impact, ligand-protein interactions, and molecular phenotypic effects of TGF-ß1 gene variants: In silico analysis with implications for idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a chronic interstitial lung disease resulting in progressively deteriorating lung function. Transforming growth factor-ß1 (TGF-ß1) belongs to the TGF superfamily and exerts a profibrotic role in promoting lung fibrosis by facilitating fibroblast infiltration and activity, extracellular matrix deposition, and inhibition of collagen breakdown, thus promoting tissue remodelling and IPF. MATERIALS AND METHODS: We evaluated the link between pathogenic TGF-ß1 SNPs and IPF pathogenesis and the structure-activity functional consequences of those SNPs on the TGF-ß1 protein. Several computational algorithms were merged to address the functional consequences of TGF-ß1 gene mutations to protein stability, putative post-translational modification sites, ligand-protein interactions, and molecular phenotypic effects. These included FATHMM, POLYPHEN2, PROVEAN, and SIFT tools (identifying deleterious nsSNPs in the TGF-ß1 gene), along with Pmut, PhD-SNP, SNAP, MutPred and the related TMHMM, MARCOIL, and DisProt algorithms (predicting structural disorders). INPS-MD was also used to evaluate the mutation-induced TGF-ß1 protein's stability and MODPRED for recognition of post-translational TGF-ß1 modification. RESULTS: In total, 14 major pathogenic variants markedly impact the destabilization of the TGF-ß1 protein, with most of these high-risk mutations associated with decreased stability of the TGF-ß1 protein as per the I-Mutant, MUpro, and INPS-MD tools. R205W, R185W, R180Q, D86Y, and I300T variants were proposed to participate in the post-translational modifications, thus affecting affect protein-ligand interactions. Furthermore, at-risk genetic variants appear to target conserved regions in the alpha helices, random coils, and extracellular loops, resulting in a varied composition of amino acids, charge, hydrophobicity, and spatial architecture. CONCLUSIONS: This study manuscript comprehensively analyzes gene variants within the TGF-ß1 gene, offering novel insights into their structural and functional implications in interacting with target sites. This study is significant for the development of targeted therapeutic strategies and personalized treatment approaches for patients with inflammatory lung diseases such as IPF.

Antibacterial, antibiofilm, and chemical profiles of Ammi visnaga L. and Foeniculum vulgare mill. Essential oils, and ADMET, molecular docking investigation of essential oils major components.

This study determined chemical profiles, antibacterial and antibiofilm activities of the essential oils (EOs) obtained by A. visnaga aerial parts and F. vulgare fruits. Butanoic acid, 2-methyl-, 3-methylbutyl ester (38.8%), linalyl propionate (34.7%) and limonene (8.5%) resulted as main constituents of A. visnaga EO. In F. vulgare EO trans-anethole (76.9%) and fenchone (14.1%) resulted as main components. The two EOs were active against five bacterial strains (Acinetobacter baumannii, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, and Staphylococcus aureus) at different degrees. The MIC values ranged from 5 ± 2 to 10 ± 2 µL/mL except for S. aureus (MIC >20 µL/mL). EOs exhibited inhibitory effect on the formation of biofilm up to 53.56 and 48.04% against E. coli and A. baumannii, respectively and activity against bacterial metabolism against A. baumannii and E. coli, with biofilm-inhibition ranging from 61.73 to 73.55%. The binding affinity of the identified components was estimated by docking them into the binding site of S. aureus gyrase (PDB code 2XCT) and S. aureus tyrosyl-tRNA synthetase (PDB code 1JIJ). trans-Anethole and butanoic acid, 2-methyl-, 3-methylbutyl ester showed relatively moderate binding interactions with the amino acid residues of S. aureus tyrosyl-tRNA synthetase. In addition, almost all predicted compounds possess good pharmacokinetic properties with no toxicity, being inactive for cytotoxicity, carcinogenicity, hepatotoxicity, mutagenicity and immunotoxicity parameters. The results encourage the use of these EOs as natural antibacterial agents in food and pharmaceutical industries.

Olea europaea L. Leaf Extract Alleviates Fibrosis Progression and Oxidative Stress Induced by Bleomycin on a Murine Model of Lung Fibrosis.

In this study, we aim to investigate the effect of industrial Olea europaea L. leaf extract (OLE) against bleomycin (BLM)-induced pulmonary fibrosis (PF) in rats. Male Wistar rats were treated with a single intratracheal injection of BLM (4 mg/kg) and a daily intraperitoneal injection of OLE (10, 20, and 40 mg/kg) for 4 weeks. Results of HPLC and LC-MS analysis revealed a large amount of oleuropein (15.43%/DW) in OLE. BLM induced apparent damage of lung architecture with condensed collagen bundles, increased lipid peroxidation which has been deduced from malondialdehyde (MDA) levels: (.9 ± .13 vs .25 ± .12 nmol/mg protein) and hydroxyproline content (.601 ± .22 vs .154 ± .139 mg/g of lung tissue) and decreased catalase (CAT) (5.93.10-5 ± 4.23.10-5 vs 6.41.10-4 ± 2.33.10-4 µmol/min/mg protein) and superoxide dismutase (SOD) (28.73 ± 3.34 vs 50.13 ± 2.1 USOD/min/mg protein) levels compared to the control. OLE treatment (40 mg/kg) stabilized MDA content (.32 ± .15 and .27 ± .13 vs .9 ± .13 nmol/mg protein), normalized SOD (61.27 ± 13.37 vs 28.73 ± 3.34 USOD/min/mg protein), and CAT (5.2.10-4 ±1.8.10-4 vs 5.93.10-5 ± 4.23.10-5 µmol/min/mg protein) activities and counteracted collagen accumulation and hydroxyproline content (.222 ± .07 vs .601 ± .22 mg/g of lung tissue) in the lung parenchyma. Finally, OLE might have a potent protective effect against PF by regulating oxidative parameters and attenuating collagen deposition, due to the existence of large amount of bioactive phenolic molecules.

Protective Effect of Tunisian Red Seaweed (Corallina officinalis) Against Bleomycin-Induced Pulmonary Fibrosis and Oxidative Stress in Rats.

Idiopathic pulmonary fibrosis is a chronic and progressive respiratory disease whose diagnosis and physiopathogenesis are still poorly understood and for which, until recently, there were no effective treatments. Over the past few decades, many studies have demonstrated that marine macroalgae such as red seaweeds are potential alternative sources of useful bioactive compounds possessing various physiological and biological activities. The present study was aimed to investigate the effect of Corallina officinalis aqueous extract (COAE) against bleomycin (BLM)-induced lung fibrosis in rat. Thus, Wistar rats were divided into 4 groups of 10 each: control, BLM (2 mg/kg), BLM/COAE-150 mg/kg and BLM/COAE-300 mg/kg once a day for 21 days. Obtained results showed that COAE is rich in phenolic compounds and exhibited relatively high antioxidant activity. COAE might significantly reduce the damage caused by BLM by rewarding the decline in weight and pulmonary index in rats given only BLM. Moreover, lungs, liver and kidneys lipid peroxidation, and sulfhydryl group levels were reversed significantly in a dose-dependent manner in the COAE-treated groups. BLM decreased superoxide dismutase (SOD) and catalase (CAT) activities, while COAE administration increased the antioxidant enzyme activities. Histopathologically, COAE attenuates the severity of the inflammatory lungs state caused by instillation of BLM in rats. These findings suggest that COAE can be a potential therapeutic candidate against BLM-induced lung fibrosis.

Protective Effect of Eucalyptus globulus Extracts Against Bleomycin-Induced Pulmonary Fibrosis in Rats.

Pulmonary fibrosis (PF) is a fibrous interstitial pneumonia that causes damage to the lung tissue and thus alters all respiratory functions. In this study, we aim to investigate the therapeutic effects of fresh leaves of Eucalyptus globulus extracts on bleomycin (BLM)-induced (PF). Twenty-four rats were divided into four groups. The control group received no treatment, the BLM group received only intratracheally BLM (2 mg/kg), the essential water of Eucalyptus globulus (EWEG) group underwent administration of BLM followed by E. globulus hydrosol (2000 mg/kg), and the essential oil of Eucalyptus globulus (EOCG) group received BLM followed by E. globulus essential oil (10 mg/kg). Gas chromatography-mass spectrometry analysis showed that the main compounds of EOEG and EWEG are eucalyptol and spathulenol. Obtained results showed that BLM-induced PF caused a large accumulation of lymphocytes and monocytes in lung bronchoalveolar lavage fluid, a high fibrosis score, and an inflammatory index coupled to an oxidative stress state assessed by an increase in lipid peroxidation and depletion of the activities of antioxidant enzymes: superoxide dismutase and catalase. Otherwise, the treatment with EWEG and EOEG reversed the deleterious effects of reactive oxygen species and the inflammation raised by BLM. E. globulus extracts could improve BLM-induced PF, thus suggesting that the latter could serve as a potential therapeutic approach for PF.

Tunisian Horehound (Marrubium vulgare) Aqueous Extract Improves Treatment of Bleomycin-Induced Lung Fibrosis in Rat.

Pulmonary fibrosis (PF) remains one of the most serious pneumopathies whose diagnosis and physiopathogenesis are still poorly understood and no treatment has been shown to be effective. Recently, many studies have shown a renewed interest in plants thanks to their pharmacological potentials, like horehound, known, for its anti-inflammatory and antioxidant activities. The present study investigated the effects of the aqueous extract of horehound (Mae) on bleomycin (BLM)-induced PF in rats. Thirty rats were divided into three groups. The control group received no treatment, the BLM group received only intratracheally BLM (2 mg/kg), and the Mae group underwent administration of BLM+ Mae (2 mL/kg) daily for 20 days. Obtained results showed that Mae, rich in polyphenols, could significantly improve the damage caused by BLM by reducing the inflammatory index and the fibrosis score, bringing the lung structure of fibrotic rats close to that of control rats. As well, Mae obviously acted on the BLM inflammatory reaction, and the counting of bronchoalveolar lavage fluid (Balf) cells showed an increase in total cell number and a decrease in the infiltration of inflammatory cells in the bronchoalveolar space. In addition, the BLM instillation was accompanied by oxidative stress in the lung, liver, and kidney tissues, proven by an increase in lipid peroxidation, as well as through depletion of superoxide dismutase (SOD) and catalase (CAT). The Mae treatment reversed all disturbances of BLM-induced oxidative stress parameters promoting antioxidant and anti-inflammatory of the latter. These findings point to Mae as a promising candidate for the treatment of pulmonary fibrosis.

Identification of genes and miRNA associated with idiopathic recurrent pregnancy loss: an exploratory data mining study.

BACKGROUND: Recurrent pregnancy loss (RPL) is a significant adverse pregnancy complication, with an incompletely understood pathology. While many entities were proposed to elucidate the pathogenic basis of RPL, only few were significant enough to warrant investigation in all affected couples.. The aim of this study was to provide novel insights into the biological characteristics and related pathways of differentially expressed miRNA (DEMs) and genes (DEGs), in RPL, and construct a molecular miRNAs-mRNAs network. METHODS: miRNAs and gene expression data were collected, and a number of DEMs and (DEGs) were obtained, and regulatory co-expression network were constructed. Function and enrichment analyses of DEMs were conducted using DIANA-miRPath. DEGs were screened, and were used in generation of protein-protein interaction (PPI) network, using STRING online database. Modularity analysis, and pathway identification operations were used in identifying graph clusters and associated pathways. DEGs were also used for further gene ontology (GO) analysis, followed by analysis of KEGG pathway. RESULTS: A total of 34 DEMs were identified, and were found to be highly enriched in TGF-ß signaling pathway, Fatty acid metabolism and TNF signaling pathway. Hub miRNAs were selected and were found to be involved in several functional pathways including progesterone-mediated oocyte maturation and Thyroid hormone signaling pathway. Five dysregulated feedback loops involving miRNA and TFs were identified and characterized. Most notably, PPI network analysis identified hub-bottleneck protein panel. These appear to offer potential candidate biomarker pattern for RPL diagnosis and treatment. CONCLUSIONS: The present study provides novel insights into the molecular mechanisms underlying RPL.

The efficacy of plant extract and bioactive compounds approaches in the treatment of pulmonary fibrosis: A systematic review.

Pulmonary fibrosis (PF) is a lethal, chronic and progressive respiratory disease leading to interstitial lung damage and serious breathing problems. The pathogenic mechanism involves activation, migration, proliferation and differentiation of fibroblasts into myofibroblats inducing extracellular matrix accumulation that destroy lung parenchyma. Available antifibrotic treatment options are limited to Pirfenidone and Nintedanib that prevent deterioration without an improvement of this disease. The use of plant extracts and natural bioactive compounds for the treatment of PF has been known for more than thirty years in China. Nowadays, phytotherapy has gained a considerable attention in the treatment of PF both in vivo and in vitro using bleomycin (BLM)-induced lung inflammation, oxidative stress and pulmonary fibrosis in rats. In this review, we aimed to focus on the protective effects and the mechanisms of action of several plant extracts described by various research works for the treatment of PF.

Nigella sativa, a traditional Tunisian herbal medicine, attenuates bleomycin-induced pulmonary fibrosis in a rat model.

The present study investigated the effects of Nigella sativa oil (NSO) on bleomycin (BLM)-induced lung fibrosis in rats. The rat model of pulmonary fibrosis (PF) was established by intratracheal instillation of BLM, and the effect of 1ml/kg oral NSO treatment once daily observed. The effect of NSO was studied over a period of 50daysusing 1H RMN analysis on the urine and broncho alveolar lavage fluid (Balf) of the rats. Histopathological (inflammation and fibrosis) and immunohistochemical (TGF-ß1 density) changes were evaluated. Results found that the BLM group showed a significant increase in inflammatory index (II), fibrosis score (FS) and TGF-ß1 distribution in the lung inflammatory infiltrate, accompanied by a decreased urinary secretion of Krebs cycle intermediates, including acetate, pyruvate, carnitine, trimethylamine-N-oxide and succinate. However, at the same time point, NSO treated rats had a reduced II and FS, and had an increased urinary secretion of histidine, fumarate, allantoin and malate. In conclusion, NSO treatment attenuated the effects of BLM-induced PF, by supporting lung, liver and kidney activity in resisting PF. These findings provide an insight into the preventive and therapeutic potential of NSO in the treatment of PF.