Phœnix dactylifera, L. seed oil alleviates Bleomycin-induced pulmonary fibrosis and oxidative stress in Wistar rats.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is the most serious form of interstitial lung disease. We aimed to investigate the effect of Phœnix dactylifera, L. seed oil (DSO) on a murine model of IPF induced by bleomycin (BLM). METHODS: Male Wistar rats were treated with a single intra-tracheal injection of BLM (4 mg/kg) and a daily intraperitoneal injection of DSO (75, 150 and 300 mg/kg) for 4 weeks. RESULTS: Our phytochemical results showed that DSO has an important antioxidant activity with a high content of polyphenols and flavonoids. High-Performance Liquid Chromatography (HPLC) and Gas chromatography/mass spectrometry (GC-MS) analysis revealed a high amount of oleic and lauric acids and a large quantity of vitamins. Histological examination showed a significant reduction in fibrosis score and collagen bands in the group of rats treated with 75 mg/kg of DSO compared to the BLM group. DSO (75 mg/kg) reversed also the increase in catalase and malondialdehyde (MDA) levels while higher doses (150 and 300 mg/kg) are ineffective against the deleterious effects of BLM. We revealed also that DSO has no renal or hepatic cytotoxic effects. CONCLUSION: DSO can play antioxidant and antifibrotic effects on rat models of pulmonary fibrosis at the lowest dose administered.

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.

Impact of respiratory muscle training on clinical and functional parameters in COVID-19 recovered patients.

Introduction: early respiratory rehabilitation is required for patients with coronavirus virus disease 2019 (COVID-19) sequelae to reduce the risk of serious disabilities after hospital discharge. Methods: it was a comparative prospective study including patients with persistent symptoms one month after discharge. The patients were hospitalized at the pneumology department D of Abderahman Mami hospital for COVID-19 pneumonia. The study involved two groups: (G1) included patients who participated in respiratory muscle training program (twice a week during 6 weeks), and a control group (G2). The groups were matched based on age, sex and body mass index (BMI). Persistent symptoms and pulmonary lung function (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), total lung capacity (TLC) and diffusion capacity for carbon monoxide (DLCO), maximal inspiratory pressure (PI max) and maximal expiratory pressure (PE max), 6 Minute Walk distance (6-MWD) at baseline and after 6 weeks were compared between the two groups. Results: the two groups of patients were comparable in terms of age, sex, BMI, comorbidities, and extent of lung computed tomography (CT) lesions. Compared to G2, a significant improvement of persistent symptoms was noted in G1, including dry cough (p=0.002), dyspnea (p=0.001), chest pain (p=0.002), and fatigue (p=0.001). The mean of percutaneous oxygen saturation (SpO2) increased from 96.68% to 97.93% (p<0.01) in G1. A significant improvement in the percentages of change of FEV1 (p=0.005), FVC (p=0.003), TLC (p<0.001), DLCO (p<0.001), and 6-MWD (p=0.015) was also noted in G1 after this program. Nevertheless, only the percentage of FEV1 (p=0.02) increased in the control group. No impact of respiratory muscle training on PI max and PE max was noted. Conclusion: the present study demonstrated a significant improvement of persistent symptoms and exercise tolerance after short-term respiratory muscle training in patients suffering from COVID-19 sequelae.

Physiopathological Mechanisms Involved in the Progression of Pulmonary Fibrosis: A Systematic Review.

Idiopathic Pulmonary Fibrosis (IPF) is a lung disease characterized by formation of fibroblast foci and honeycomb lesions in the pulmonary parenchyma. The physiopathological mechanisms involved in the development of fibrosis and architectural disorganization are still imperfectly elucidated. In fact, lesion formation is irreversible and no treatment, to date, has been shown to be effective (30% of patients die within 5 years of the onset of the disease). The long-held concept of chronic inflammation leading to fibrosis is still controversial. Indeed, recent data suggest that the physiopathology of this disease is the product of fibroblast dysfunction rather than the result of an inflammatory imbalance. This concept supports the parallel involvement of three main factors: epithelial damage, angiogenesis and oxidative stress. In this review we highlighted the different factors and the ethiopathogenic pathways involved in the fibrotic process, in order to increase our understanding of the mechanisms involved in this pulmonary pathology.

Thymus Vulgaris Inhibit Lung Fibrosis Progression and Oxidative Stress Induced by Bleomycin in Wistar Rats.

Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating and fatal disease characterized by aberrant fibroblasts proliferation, oxidative stress and collagen accumulation in the interstitial tissue. We aimed to evaluate in the present study the efficacy of Thymus vulagris extract (TVE) on an experimental model of pulmonary fibrosis induced by bleomycin (BLM). Wistar rats were given a single dose of BLM (4 mg/kg, intratracheal), while TVE (50, 100 and 200 mg/kg, intraperitoneal) was administered 3 days later and continued for 4 weeks. We reveled by HPLC analysis an important amount of phenolic bioactive compounds such as rosmarinic and vanillic acids. Our results showed a significant decrease of catalase and superoxide dismutase activities and an increase in lipid peroxidation compared to control group after BLM injection. Treatment with TVE (200 mg/kg) was able to normalize the level of these oxidative markers and to decrease collagen accumulation compared to BLM group. Moreover, this high dose of TVE have no renal or hepatic cytotoxic effects. This study allowed us to conclude that thyme extract has a strong antioxidant and antifibrotic activities due to its high content of polyphenols.

Industrial Elimination of Essential Oils from Rosmarinus Officinalis: In Support of the Synergic Antifibrotic Effect of Rosmarinic and Carnosic Acids in Bleomycin Model of Lung Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by collagen deposition as a consequence of excessive lung fibroblasts and myofibroblasts proliferation. We aimed to investigate for the first time the effect of rosemary leaf extract rich with carnosic acid (CA) or rosmarinic acid (RA), after industrial elimination of essential oils, against bleomycin (BLM)-induced lung fibrosis in rats. Male Wistar rats were given a single dose of BLM (4 mg/kg, intratracheal), while CA rich extract, RA rich extract or the combination RA/CA rich extracts (10, 75 and 150 mg/kg, intraperitoneal) were administered 3 day later and continued for 4 weeks. We reveled by HPLC an important similar amount of phenolic compounds such as pyrogallol, vanillic, gallic and ellagic acids in both rosemary extracts. BLM induced lung fibrotic foci and disturbance in superoxide dismutase, catalase and malondialdehyde levels. At 10 mg/kg, both rosemary extracts administrated alone or in combination alleviated synergistically lung fibrosis and ameliorated oxidative changes induced by BLM. In conclusion, industrial elimination of essential oils from rosemary allowed us to obtain two extracts with potent antifibrotic activities due to the large amount of RA and CA that appear much higher and effective than wild rosemary extract.

Paradoxical bronchoconstriction caused by ß2-adrenoceptor agonists.

INTRODUCTION: Salbutamol and terbutaline are short-acting ß2 adrenergic agonists that produce bronchial smooth muscle relaxation and are widely used in obstructive pulmonary diseases. Nevertheless, their use has been the cause of a paradoxical bronchoconstriction, which is a rare and potentially serious adverse reaction. The aim of this study is to report a case of paradoxical bronchoconstriction caused by ß2 adrenergic agonists. METHODS: This case is about a 50-year-old asthmatic patient who describes a history of repeated acute asthma attacks after salbutamol inhalation or terbutaline nebulization. A double-blind crossover study was performed over 3 days, in order to compare the effects of each bronchodilator. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and maximal expiratory flow 25-75 (MEF25-75) were measured. RESULTS: On the first day, a bronchoconstriction caused by deep and repeated inhalations was eliminated. On the second day, an airway obstruction was confirmed by a decrease in FEV1 at 40% from baseline values after nebulization of a standard dose of terbutaline. On the third day, a spirometry was performed before and after nebulization of a standard dose of ipratropium bromide, and there were no significant changes in the spirometric parameters. Finally the patient was discharged with a written warning mentioning the danger of salbutamol and terbutaline use. CONCLUSION: Salbutamol and terbutaline are generally well-tolerated ß2 adrenergic agonists. Nevertheless, in rare cases, these substances can cause a paradoxical bronchoconstriction. Doctors must therefore remain vigilant about its side effect and possibly investigate each case.

Comparison of the Protective Effect of Salvia officinalis and Rosmarinus officinalis Infusions Against Hepatic Damage Induced by Hypotermic-Ischemia in Wistar Rats.

We aimed to evaluate, in this study, the effect of Rosmarinus officinalis L. and Salvia officinalis L. in the amelioration of liver hypothermic conservation in male wistar rats. Livers from each rat were collected and preserved for 24 h at 4 °C in a Krebs solution with or without increasing doses of sage or rosemary infusions (25, 50, and 100 mg/mL). Liver hypothermic conservation induced a decrease in the activity of superoxide dismutase, catalase, and glutathione peroxidase and a significant increase in lipid peroxidation. S. officinalis L. infusion at 25 mg/mL normalized this oxidative disturbance but appears toxic at 50 and 100 mg/mL due to the presence of large amount of pyrogallol which contribute to the cytoplasmic alteration of hepatocytes. The addition of different doses of R. officinalis L. infusion induced an increase in catalase and glutathione peroxidase activities and a decrease in lipid peroxidation with an amelioration of cellular architecture. In conclusion, increasing doses of R. officinalis L. infusion protect against hepatic hypotermic-ischemia while S. officinalis L. infusion could have an hepatoprotective role when administrated at lower dose.

Salvia officinalis attenuates bleomycin-induced oxidative stress and lung fibrosis in rats.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive and irreversible fibroblasts proliferation leading to significant respiratory insufficiency. This study was designed to investigate the effect of sage infusion against bleomycin (BLM)-induced lung fibrosis in rats. Male Wistar rats were given a single dose of BLM (4 mg/kg, intratracheal), while sage infusion (50, 100 and 150 mg/kg, intraperitoneal) was administered 3 day later and continued for 4 weeks. We reveled by HPLC and LC-MS methods an important amount of phenolic bioactive compounds such as vanillic, gallic, ellagic, rosmarinic and carnosic acids. BLM induced collagen deposition, increased lipid peroxidation (MDA) and decreased superoxide dismutase (SOD) and catalase (CAT) activities. Only sage infusion at 150 mg/kg normalized MDA and antioxidant enzyme levels (SOD and CAT) and reduced significantly lung fibrosis. Our results showed also that this high dose have no renal or hepatic cytotoxic effect. In conclusion, sage can protect against BLM-induced murine lung fibrosis and oxidative stress due to the large content of bioactive phenolic compounds.

Does Curcuma longa root powder have an effect against CCl4-induced hepatotoxicity in rats: a protective and curative approach.

This study was conducted to investigate potentially protective and curative effects of Curcuma longa root (turmeric) powder on CCl4-induced hepatotoxicity in rats. Turmeric was administered before (preventive effect) or after (curative effect) treatment with CCl4. Total phenolic and flavonoid levels were 26.35 mg GAE/g and 12.35 mg CE/g, respectively. Using HPLC analysis, turmeric powder was rich in curcumin (62.97%), demethoxycurcumin (20.86%) and bisdemethoxycurcumin (16.17%). Curcuma longa powder showed important in vitro antioxidant activities. Results showed that the activities of aspartate aminotransaminase and alanine aminotransaminase, and the levels of bilirubin and serum lipids were increased in CCl4-treated animals. However, total protein and albumin levels and antioxidant enzyme activities were decreased. Turmeric administration, before or after CCl4 treatment, significantly decreased the activities of marker enzymes and lipid levels in serum. Moreover, total protein and albumin contents were restored to nearly normal levels after turmeric administration accompanied with increase of antioxidant enzymes activities.

Effect of Phoenix dactylifera L. Sap Against Bleomycin-Induced Pulmonary Fibrosis and Oxidative Stress in Rats: Phytochemical and Therapeutic Assessment.

Lung fibrosis is a lethal interstitial disease characterized by massive proliferation of fibroblast inducing excessive collagen deposition. We aimed to investigate whether Date palm sap (DPS) can play a protective effect on bleomycin (BLM)-induced lung fibrosis in rats. MaleWistar rats were given single dose of BLM (4 mg/kg, intra-tracheal), while DPS (45 mg/kg, intraperitoneal) was administered three days later and continued for three weeks (BLM/DPS group). Characterization of phenolic compounds in DPS was evaluated by LC-HRESIMS analysis. Hematoxylin-eosin and Masson's Trichome staining were used for the revelation of lung architecture, collagen deposition, and fibrosis score. Antioxidant effects of DPS and hydroxyproline content in lung tissues were studied using standard spectrophotometric methods. We reveled by liquid chromatography-high-resolution electrospray ionization mass spectrometry (LC-HRESIMS) an important amount of vitamins and phenolic compounds in DPS. BLM increased lipid peroxidation (MDA) and superoxide dismutase (SOD) levels and decreased catalase (CAT) activity. BLM also induced inflammation and accumulation of bundles of collagen in lung. DPS treatment normalized MDA, SOD, and CAT levels, decreased hydroxyproline level and morphological lesions induced by BLM. In conclusion, DPS has a protective effect against BLM-induced murine lung fibrosis due to its richness in phenolic compounds and vitamins.

Rosmarinic acid potentiates carnosic acid induced apoptosis in lung fibroblasts.

Pulmonary fibrosis is characterized by over-population and excessive activation of fibroblasts and myofibroblasts disrupting normal lung structure and functioning. Rosemary extract rich in carnosic acid (CA) and rosmarinic acid (RA) was reported to cure bleomycin-(BLM)-induced pulmonary fibrosis. We demonstrate that CA decreased human lung fibroblast (HLF) viability with IC50 value of 17.13±1.06 µM, while RA had no cytotoxic effect. In the presence of 50 µM of RA, dose-response for CA shifted to IC50 value of 11.70±1.46 µM, indicating synergic action. TGFß-transformed HLF, rat lung fibroblasts and L929 cells presented similar sensitivity to CA and CA+RA (20µM+100µM, respectively) treatment. Rat alveolar epithelial cells died only under CA+RA treatment, while A549 cells were not affected. Annexin V staining and DNA quantification suggested that HLF are arrested in G0/G1 cell cycle phase and undergo apoptosis. CA caused sustained activation of phospho-Akt and phospho-p38 expression and inhibition of p21 protein.Addition of RA potentiated these effects, while RA added alone had no action.Only triple combination of inhibitors (MAPK-p38, pan-caspase, PI3K/Akt/autophagy) partially attenuated apoptosis; this suggests that cytotoxicity of CA+RA treatment has a complex mechanism involving several parallel signaling pathways. The in vivo antifibrotic effect of CA and RA was compared with that of Vitamine-E in BLM-induced fibrosis model in rats. We found comparable reduction in fibrosis score by CA, RA and CA+RA, attenuation of collagen deposition and normalization of oxidative stress markers. In conclusion, antifibrotic effect of CA+RA is due to synergistic pro-apoptotic action on lung fibroblasts and myofibroblasts.

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.

Prophylactic and curative effect of rosemary leaves extract in a bleomycin model of pulmonary fibrosis.

CONTEXT: Pulmonary fibrosis is a devastating disease without effective treatment. Rosemary is appreciated since ancient times for its medicinal properties, while biomolecules originated from the plant have an antioxidant and antifibrotic effect. OBJECTIVE: The effects of Rosmarinus officinalis L. (Lamiaceae) leaves extract (RO) on bleomycin-induced lung fibrosis were investigated. MATERIALS AND METHODS: Male Wistar rats were given a single dose of bleomycin (BLM, 4 mg/kg, intratracheal), while RO (75 mg/kg, intraperitoneal) was administered 3 days later and continued for 4 weeks (BLM/RO1-curative group). Alternatively, RO was administered 2 weeks before BLM and continued 15 days thereafter (BLM/RO2-prophylactic group). Antioxidant activities of RO and lung tissues were studied by standard methods. Histological staining revealed lung architecture and collagen deposition. RO was characterized for its polyphenol content and by high-performance liquid chromatography. RESULTS: RO polyphenol content was 60.52 mg/g of dry weight, carnosic and rosmarinic acids being major components (6.886 and 2.351 mg/g). Antioxidant effect of RO (DPPH and FRAP assay) expressed as IC50 values were 2.23 µg/mL and 0.074 µg/mL, respectively. In BLM/RO1 and BLM/RO2 lung architecture was less compromised compared to BLM, which was reflected in lower fibrosis score (2.33 ± 0.33 and 1.8 ± 0.32 vs 3.7 ± 0.3). Malondialdehyde levels were attenuated (141% and 108% vs 258% of normal value). Catalase and glutathione-S-transferase activities were normalized (103% and 117% vs 59%, 85% and 69% vs 23%, respectively). DISCUSSION AND CONCLUSION: RO has a protective effect against BLM-induced oxidative stress and lung fibrosis due to its phenolic compounds.

Idiopathic pulmonary fibrosis:Pathophysiological data.

Idiopathic pulmonary fibrosis is the most common of the idiopathic interstitial pneumonias. The role of inflammation in idiopathic pulmonary fibrosis (IPF) is controversial. If inflammation were critical to the disease process, lung pathology would demonstrate an influx of inflammatory cells, and that the disease would respond to immunosuppression. The classic pathology does not display substantial inflammation, and no modulation of the immune system is effective as treatment. Recent data suggest that the pathophysiology of the disease is more a product of fibroblast dysfunction than of dysregulated inflammation. The concept of epithelial-mesenchymal cell transition has recently received much attention; this transition appears to play a greater role in the pathogenesis than inflammation. It's suggested that inflammation is indeed a critical factor in IPF and proposed five potential nontraditional mechanisms for the role of inflammation in the pathogenesis of IPF: the direct inflammatory hypothesis, the matrix hypothesis, the growth factor-receptor hypothesis, the plasticity hypothesis, and the vascular hypothesis.

Relevance of carnosic acid to the treatment of several health disorders: Molecular targets and mechanisms.

Carnosic acid is a phenolic diterperne compound found in abundance in sage and rosemary, which are both widely used in traditional medicine. Research over the past decade indicates that carnosic acid has multiple bioactive properties including antioxidant, anti-inflammatory and anticancer activities among others. This review summarizes the current in vitro and in vivo data about the efficacy of carnosic acid in the prevention or treatment of various experimental health disorders. The analysis of the literature allows an insight into the participation of numerous signaling pathways modulated by carnosic acid, into its synergistic potential and, thus, into the divergence in cellular mechanisms of action of this molecule.

Evaluation of nutritional status and body composition of young Tunisian weightlifters.

AIM: to study the quantitative and qualitative aspects of daily spontaneous nutrition as well as anthropometric characteristics and body composition of young Tunisian weightlifters. METHODS: Thirty one boys aged between 14 and 18 years, practicing for two hours a day, six days a week in the four weightlifting clubs in Tunis were invited to attend an evaluation session for a food survey (3 days recall, with consumption frequency over a period of 7 days) and the assessment of anthropometric measurements (Weight, height and skinfolds). RESULTS: Energy intake was acceptable. However, an imbalance nutrient intake was revealed. Concerning macronutrient, fat and protein were above the recommended allowances (p<0.01). Further, the percentage of saturated fatty acids was significantly above the recommended values while the percentages of polyunsaturated fatty acids and monounsaturated fatty acids were restricted. Regarding the micronutrient, the intake of calcium, magnesium and potassium were restrictive (p<0.01). As for the fluid intake, a limited contribution was observed (p<0.01). Several correlations between body composition and dietary intake have been found. CONCLUSION: Nutritional education may lead these young weightlifters to adopt appropriate nutritional habits to optimize dietary intake. This fact could be compromising of a more suitable body composition and could have a positive bearing on athletic performance.

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.