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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.

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...

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive and irreversible fibroblasts proliferation leading to significant respiratory insufficiency. This study wa...

Aims and Objectives: Oxidative stress is one of the most important etiopathogenic axes in pulmonary fibrosis. In this study, we aimed to investigate the effect of Tunisian Olive Leaf Extract (TOLE) rich in bioactive compounds more particularly polyphenols on oxidative stress and therefore on lung fibrosis induced by Bleomycin (BLM) in rats. Methods: Animals were randomly divided into 4 groups of 8 rats each. G1: Control group, G2: BLM group, G3: TOLE group, G4: BLM + TOLE group. BLM was administered by a single intra tracheal injection (4 mg/Kg) to G2 and G4. TOLE was administered intraperitoneally at a dose of (10 mg / kg/day) for 3 weeks to G3 and G4. The later received TOLE 3 days after BLM injection. At the end of the protocol, all rats were sacrificed and lungs were extracted. Antioxidant effects of TOLE in lung tissues were studied using standard spectrophotometric methods and fibrosis was assessed by histological analysis conforming to Ashcroft score. Results: Before starting the therapeutic protocol, analysis of TOLE by HPLC and LC-MS methods revealed an important amount of phenolic bioactive compounds such as oleuropein and hydroxytyrosol. At the end of protocol, we noticed that TOLE treatment normalized MDA and antioxidant enzyme levels (SOD and CAT) and decreased significantly fibrosis score in G4 compared to G2. Conclusion: These data are promising and should be complemented by further studies evaluating the dose response effect of TOLE on fibrotic process in BLM induced lung fibrosis.

Hypericum genus is traditionally known for its medicinal use and its therapeutic and antioxidant effects. However, the toxic effect of this plant has not been much explored. Our study aimed at investigating the effect of Hypericum humifusum (Hh) leaf extracts on oxidative stress parameters in male rats. For it, we first focused on the phytochemical analysis of the aqueous and methanolic extracts of Hh leaves. Hence, Wistar rats were treated per gavage for 30 days and divided into Control (1 mL/rat, distilled water), A200 group (200 mg/kg body weight (bw) aqueous extract), A400 group (400 mg/kg bw aqueous extract), M10 group (10 mg/kg bw methanolic extract), M20 group (20 mg/kg bw methanolic extract). The phytochemical analysis revealed the presence of tannins, flavonoids, steroids, carbohydrates, and phenolic compounds. Biochemical and histological investigations were performed in plasma and liver tissue. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) levels. At the same time, alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) were assayed in plasma samples. Histological study was also conducted in liver. We showed that Hh extracts reduced relative liver weight and increased ALT, AST, LDH activities in treated groups compared to control group. These results were associated with an increase of MDA levels and a decrease of antioxidant enzyme activities (CAT and SOD) in liver tissues of treated rats. Histology of liver demonstrated several alterations showing necrosis, altered hepatocytes and lymphocyte migration mainly in A200 group and dilated sinusoids, foamy appearance of hepatocytes and lymphocyte accumulation in the other treated groups. This original work indicated that chronic consumption of Hh leaf extracts has no antioxidant effect but instead it induces oxidative stress and enhances markers of cell damage which was confirmed by histological study of liver rats.

Recently, there has been increasing interest in Hypericum ( Hypericaceae ) genus. The first part of the present study focused on the phytochemical analysis of the methanolic and aqueous extracts of Hypericum humifusum leaves. The second part of the study investigated the effect of Hypericum humifusum leaf extracts on male reproductive parameters. 30 male rats were grouped into control (1 mL/rat, distilled water), treated by 200 mg/kg body weight (bw) aqueous extract (A200), 400 mg/kg bw aqueous extract (A400), 10 mg/kg bw methanolic extract (M10) and 20 mg/kg bw methanolic extract (M20) groups. The phytochemical analysis revealed the presence of tannins, flavonoids, steroids, carbohydrates, and phenolic compounds. After thirty-day treatment, body and reproductive organs were weighed. Testes in all rat groups were processed for biochemical assays and histopathological examinations. Epididymis sperm analyses were also performed. Testicular tissue homogenate samples were used for Malondialdehyde (MDA), catalase and superoxide dismutase (SOD) measurements. We showed that Hh extracts induced a severe seminiferous tubular damage with an increase in the percentage of empty seminiferous tubules. Epididymis sperm analysis revealed a significant reduction in density and viability of sperm with alteration of spermatozoa morphology. Also, we found that Hh leaf extracts decreased plasma total cholesterol, HDL-cholesterol and triglycerides levels. These results were associated with an increase of MDA levels and a decrease of catalase and SOD activities in testis tissues. Our finding revealed that chronic consumption of Hh extracts induces disruption of normal spermatogenesis by alteration of sperm density, viability, and morphology. This action may be due to an inhibition of the antioxidant-defense system.

The impact of garlic, known for its antioxidant activities, on iron metabolism has been poorly investigated. The aim of this work was to study the effect of crude garlic pre-treatment on iron-mediated lipid peroxidation, proliferation and autophagy for 5 weeks. Rats were fed distilled water or garlic solution (1 g/kg body weight) by gavage for the first 3 weeks as pre-treatment and received a basal diet supplemented or not with ferrous sulfate (650 mg Fe/kg diet) for the last 2 weeks of treatment. Immunohistochemistry labeling and ultrastuctural observations were used to evaluate the iron deleterious effects in the liver. Iron supplementation induced cell proliferation predominantly in non parenchymal cells comparing to hepatocytes, but not apoptosis. In addition, iron was accumulated within the hepatic lysosomes where it triggers autophagy as evidenced by the formation of autophagic vesicles detected by LC3-II staining. It also induced morphologic alterations of the mitochondrial membranes due to increased lipid peroxidation as shown by elevated iron and malondialdehyde concentrations in serum and tissues. Garlic pre-treatment reduced iron-catalyzed lipid peroxidation by decreasing the malondialdehyde level in the liver and colon and by enhancing the status of antioxidants. In addition, garlic reduced the iron-mediated cell proliferation and autophagy by lowering iron storage in the liver and protected mitochondrial membrane. Based on these results, garlic treatment significantly prevented iron-induced oxidative stress, proliferation and autophagy at both biochemical and histological levels due to its potent free radical scavenging and antioxidant properties.

Garlic is regularly consumed and is known to have diverse biologic activities, particularly due to its antioxidant properties. In this study, we hypothesized that crude garlic can prevent iron-mediated oxidative stress in a rat model of nutritional iron overload, and we used an in vitro model to confirm the results. For the in vivo studies, rats received a basal diet supplemented with or without carbonyl iron (3%) and were fed distilled water or garlic solution (1g/kg body weight) by gavage for 3 weeks. The presence of both garlic and iron led to a 2-fold increase in plasma iron and a 50% increase in liver iron as compared with iron alone. However, garlic did not offer any protection against iron-induced oxidative stress. Duodenal divalent metal transporter-1 mRNA expression was fully repressed by iron and by the combined treatments but was also reduced by garlic alone. To confirm these data, we tested the effect of diallyl disulfide, one of the active components in garlic, in vitro on polarized Caco-2 cells. A 24-hour treatment decreased iron uptake at the apical side of Caco-2 cells but increased the percentage of iron transfer at the basolateral side. This probably resulted from a modest induction of ferroportin mRNA and protein expression. These results suggest that garlic, when given in the presence of iron, enhances iron absorption by increasing ferroportin expression. The presence of garlic in the diet at the dose studied does not seem to protect against iron-mediated oxidative stress.

Many researchers have focused on the preventive and curative effects of garlic (Allium sativum), particularly on cardiovascular diseases and cancer. However, its impacts on the male reproductive system have not been clearly defined. In this study, the effect of chronic consumption of two garlic fractions was tested: one soluble in water (aqueous solution obtained by grinding and centrifugation) and the other one precipitated by ethanol (alcoholic precipitate obtained by precipitation of the aqueous solution), on different variables of male rats' reproductive functions. These two fractions were targeted to try to identify the nature of the active garlic compounds responsible for the different modifications observed on testicular parameters. The observation of seminiferous tubules of rats treated with garlic fractions showed an increased number of tubules deprived of spermatozoa. In addition, garlic fractions induced apoptosis of testicular germ cells (TdT-mediated dUTP-X nick-end labeling [TUNEL] approach) and a decrease of serum testosterone levels and seminiferous tubule DNA concentrations. In summary, our histological and molecular results suggest that one or several substances, soluble in water and precipitated by alcohol, impaired spermatogenesis.

International audience; It has been suggested that hormonally controlled submandibular salivary gland (SSG) development and secretions may be affected by endocrine disruptor compounds. We investigated the effects of oral gestation-lactation exposure to 1 mg/kg body weight daily dose of the estrogenic soy-isoflavone genistein and/or the anti-androgenic food contaminant vinclozolin in female rats. The SSGs of female offspring were collected at postnatal day 35 to study gland morphogenesis and mRNA expression of sex-hormone receptors and endocrine growth factors as sex-dependent biomarkers. Because of high expression in neonatal SSG, mRNA expression of transforming growth factor α was also studied. Exposure to genistein, vinclozolin, or a genistein+vinclozolin mixture resulted in significantly lower numbers of striated ducts linked to an increase in their area and lower acinar proliferation (Ki-67–positive nuclei). Exposure to the mixture had the highest significant effects, which were particularly associated with repression of epidermal growth factor, nerve growth factor, and transforming growth factor α expression. In conclusion, early exposure to low doses of genistein and vinclozolin can affect glandular structure and endocrine gene mRNA expression in prepubertal SSG in female rats, and the effects are potentialized by the genistein+vinclozolin mixture. Our study provides the first evidence that SSG are targeted by both estrogenic and anti-androgenic disrupting compounds and are more sensitive to mixtures.