Chemotherapeutic effect of Ulmus pumila leaves methanolic extract against N-methyl-N-nitrosourea-induced mammary carcinoma in female rats: An in vitro and in vivo study

Searching for a chemopreventive agent is an important approach for breast cancer management. The aim of the study was to evaluate the chemopreventive potential of Ulmus pumila (UP) leaves extract on breast tumorigenesis induced in experimental animals by N-methyl-N-nitrosourea. This target was undertaken through preparing several extracts from the fresh leaves of UP using different solvents against the breast adenocarcinoma cell line (MCF-7). Our in vitro results demonstrated that the methanolic extract of UP (UPME) showed the highest cytotoxic activity against the growth of MCF-7 cells. After determination of UPME safe dose (1/10) of a lethal dose, the in vivo results revealed that UPME treatment significantly decreased the activities of liver enzymes, kidney function, cancer antigen 15-3 (CA 15-3) level, urokinase plasminogen activator, heparanase, basic fibroblast growth factor, B-cell leukemia lymphoma 2, and cyclooxygenase-2. By contrast, total antioxidant capacity (TAC) was increased in therapeutic, protective, and prophylactic groups as compared to the tumor group. These improvements were supported with histopathological changes. These results indicated that the chemotherapeutic potential of UPME through stimulation of apoptosis and the suppression of angiogenesis, proliferation, and metastasis.

Subchronic toxicity of propyl paraben in adult male rats

In the current study, daily per os administration of propyl paraben [n-propyl-p-hydroxybenzoate] to adult male rats for four consecutive weeks induced severe hepatotoxicity as revealed by the significant elevation in serum marker enzymes along with a significant decrease in serum protein and its fractions. Furthermore, propyl paraben administration disturbed steroid hormones balance by suppressing serum testosterone level, with a concomitant increase in serum estradiol and an ultimate decrease in testosterone/estradiol ratio. Hepatic and testicular toxicity was furtherly attributed to oxidative stress induction, since propyl paraben altered the oxidant/antioxidant balance in both tissues. Signs of toxicity and histopathological changes in the liver and testes were observed by light microscopy of haematoxylin and eosin-stained sections. In conclusion, our data demonstrate the potency of propyl paraben as an endocrine disruptor to induce disturbances in normal steroid balance in adult male rats. In addition, the induced oxidative stress represents a common mechanism of propyl paraben toxicity in hepatic and testicular tissues

Role of calcium in enhancing the activity and thermal stability of a new cationic peroxidase purified from euphorbia tirucalli latex

A new cationic peroxidase from Euphorbi and firucalli [pencil cactus] latex was purified to homogeneity using benzene fractionation, gel filtration and cation-exchange chromatography. The purified enzyme was found to be monomeric with a molecular weight of 44 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE]. The purified enzyme had a broad specificity towards some phenolic substrates in the order of 2,2'-azino-bis [3-ethylbenzothiazoline-6-sulfonicacid] [ABTS] > guaiacol > 0-phenylenediamine > 4-aminoantipyrene, whereas no affinity towards ascorbic acid and o-dianisidine was recorded. The enzyme had pH and temperature optima at 7.0 and 40°C, respectively. Study of kinetic parameters demonstrated that ABTS had the highest affinity towards ELP, where K[m], F[max] and V[ms]/K[m] values were 0.503 mM, 500 U/assay and 994.04 U/mM, respectively. ELP was stable from 10°C up to 60°C and lost about 70% of its activity at 70°C. The thermal inactivation profile of ELP in absence of Ca[2+] is biphasic and characterized by a rapid decline in activity on exposure to heat, followed by a more gradual decrease in activity on continued exposure. However, the purified enzyme exhibited increased thermal stability in the presence of calcium ions. Furthermore, the activity of purified enzyme was enhanced by 550% in the presence of 15 mM CaCl[2], suggesting a pivotal role for Ca[2+] in conferring structural stability to the heme environment and in retaining the active site of ELP. Most of the examined metal ions [except for Ca and Mg] and compounds had differential inhibitory effects on ELP activity. In conclusion, a locally available plant [Euphorbia tirucalli] could be a potential candidate source for peroxidase, the most widely used enzyme in industrial and biomedical applications. In addition, calcium was found to be essential for enhancing enzymatic activity and thermal stability of the purified Euphorbia tirucalli latex peroxidase

Cardioprotective activity of polysaccharopeptides extracted from pleurotus ostreatus mycelium in a doxorubicin-rat model

The present study was undertaken to investigate the possible abatement of doxorubicin-induced cardiomyopathy in the rat by polysaccharopeptides extracted from the culture broth of Pleurotus ostreatus mycelium. It was found that polysaccharopeptides given as protection before doxorubicin intoxication normalized the levels of serum total creatine kinase, aspartate aminotransferase and lactate dehydrogenase activities, in addition to malondialdehyde, reduced glutathione, as well as superoxide dismutase and catalase activities in the heart tissue. Nitric oxide and tumor necrosis factor-alpha concentrations were persistently reduced in the heart tissue, while interferon-gamma concentration was insignificantly changed, compared to controls. Light microscopic examination of haematoxylin and eosin-stained sections of the left ventricles showed normal structure of the cardiac myocytes, except for a slight but significant decrease in their thickness, compared to controls. Pretreatment with mycelial polysaccharopeptides provided a potential protective effect against doxorubicin-induced oxidative stress in rats