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.

A new Thiocyanoacetamide protects rat sperm cells from Doxorubicin-triggered cytotoxicity whereas Selenium shows low efficacy: In vitro approach.

Doxorubicin (DOX) exhibits a wide-ranging spectrum of antitumor activities which maintain its clinical use despite its devastating impact on highly proliferating cells. The present work was designed to develop a new approach which aims to protect male germ cells from DOX cytotoxicity. Thus, an assessment of the protective potential of a new thioamide analog (thiocyanoacetamide; TA) compared to selenium (Se) was performed in rat sperms exposed to DOX in vitro. Oxygen consumption rate (OCR) was measured after exposure to three different doses (0.5, 1, 1.5 and 2 µM) of DOX, Se or TA, and the suitable concentrations were selected for further studies afterwards. Motility, OCR in a time-dependent manner, glucose extracellular concentration and lipid peroxidation (LPO) were measured. Fatty acid (FA) content was assessed by gas chromatography (GC-FID). Cell death, superoxide anion (O2-), mitochondrial membrane potential (MMP), and DNA damage were evaluated by flow cytometry. TA association with DOX increased OCR and glucose uptake, improved cell survival and decreased DNA damage. The co-administration of DOX with Se increased OCR, significantly prevented O2- overproduction, and decreased LPO. Collected data brought new insights regarding this transformed TA, which showed better efficiency than Se in reducing DOX cytotoxic stress in sperms.

Development and validation of a colorimetric method for the quantitative analysis of thioamide derivatives.

Thioamides (Thm) have diverse biological activities. This work presents the development and validation of simple, rapid and accurate spectrophotometric method for the analysis of Thm derivatives in pure form and in plasma. This spectrophotometric method has not been used before for determination of Thm. A review of the literature revealed that the monitoring of S- group assay is based on the reaction with DTNB according to the Ellman method to form a yellow complex which absorbs at 412 nm. To assay the thioamides according to this method it is necessary to make the basic medium have S- to react with the DTNB. Experimental conditions affecting the color development were studied and optimized. The proposed spectrophotometric procedures were effectively validated with respect to linearity, ranges, precision, accuracy, specificity, robustness, detection and quantification limits. Calibration curves of the formed colored product with DTNB showed good linear relationships over the concentration ranges (0, 50, 100, 500, 1000, 1500 mg/L). The proposed method was successfully applied to the assay of Thm monitoring with good accuracy. The principal advantages of the proposed method were rapidity and suitability for the routine quality control assay of the drug alone and in monitoring form without interference.

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.

Gold and Female Reproductive Organs: an Ultrastructural Study.

Gold, a heavy yellow-colored metal, is usually found in nature as a metallic element or as salts. This noble metal historically had a reputation as an anti-inflammatory medicine for rheumatoid arthritis, a nervine, and a remedy for nervous disorders, as well as a potential anticancer agent. It has also been used as component in dental restorations and in implant materials. The present study was undertaken to point out histological and ultrastructural effects of gold, administered by intraperitoneal route, in pregnant female reproductive organs (ovary and uterus), in order to clarify its side effects on the reproductive function. Using the transmission electron microscopy (TEM), the ultrastructural investigations of both ultrathin ovarian and uterine sections of treated pregnant rats revealed the existence of numerous heterogeneous clusters with very electron-dense inclusions characterized by various aspects in the lysosomes of granulosa, theca interna cells, and theca externa cells. Degeneration of these tissues, like cell vacuolization, marked expansion of the endoplasmic reticulum, mitochondrial alterations, and necrotic foci, were also highlighted. Moreover, huge phagolysosomes and high numbers of eosinophils as signs of inflammation were also identified especially in endometrial and myometrial cells of gold-treated rats. The ultrastructural investigations of reproductive organ sections of control pregnant rats showed a normal ultrastructural aspect and no loaded lysosomes. These results speculated the toxicity of gold at the used dose. The observed signs of toxicity allowed concluding that the important role of lysosome in the sequestration of this element under an insoluble form in all categories of cells in the studied tissues does not seem to be efficient.

Selenium and a newly synthesized Thiocyanoacetamide reduce Doxorubicin gonadotoxicity in male rat.

Despite its deleterious effect on healthy cells and highly regenerating cells such as spermatozoa, Doxorubicin (DOX) is still one of the most used anticancer drugs in the last decades. The present work aimed to investigate the ability of the selenium (Se) and the thiocyanoacetamide (T) to reduce DOX toxicity in gonad. Adult male rats were treated with DOX intravenously (i.v.) at 3.7mg/kg/week associated with Se intragastrically (i.g.) at 0.2mg/kg/day or with T at 10mg/kg/day i.g. After 47days of treatment, sperm quality, biochemical parameters, blood cell count and histological changes in liver, testis and epididymis were assessed. The results showed a poor sperm quality, a perturbation of ionic stability and a significant alteration of lipid metabolism and hematological parameters after the sub-chronic administration of DOX. In testis, DOX exerted serious epithelium damage and numerous seminiferous tubules did not present a normal spermatogenesis. In epididymis, epithelium was altered and mastocytes infiltrated the interstitium. DOX did not exert any significant change in liver except dilatations of sinusoid capillaries. DOX association with Se or T reduced its toxicity on some hematological and biochemical parameters. Both combined treatment improved sperm quality and partially restored spermatogenesis as well as testis and epididymis' normal aspect. These findings brought new sights regarding the effect of Se and a new derivative of T in a combined treatment with DOX on germ cells, gonad and liver. The support of these relevant outcomes with further in vitro studies is necessary to highlight the accurate process involved in Se or T protection against DOX induced damages.