Hepatotoxic and hematotoxic effects of sage oil-loaded ifosfamide nanoemulsion in Ehrlich ascites carcinomabearing mice

Purpose: To investigate the hepatotoxic and hematotoxic effects of sage oil-loaded ifosfamide (IFO) nanoemulsion (NE) in Ehrlich ascites carcinoma (EAC)-bearing mice. Methods: Ifosfamide (IFO) was loaded into a NE containing sage oil, and its hepatotoxic and hematotoxic effects were assessed in EAC-bearing mice. Female Swiss albino mice (n = 50) weighing 25 - 30 g (mean weight = 27.5 ± 2.50 g) were randomly assigned to five groups of ten mice each. With the exception of group 1, the mice were inoculated intraperitoneally (i.p.) with 2.5 × 106 EAC/mouse for 48 h. Group I served as negative control, C (-); group II served as positive control, C (+); while groups III - V were treated i.p. with 60 mg/kg IFO in 0.3mL water (free-IFO); 0.3 mL NE (SAGE-NANO), and 60 mg/kg IFO in 0.3 mL SAGE-NANO (SAGE-IFO), respectively. The treatments were administered for three days. Results: Treatment with 60 mg/kg bwt IFO (free-IFO) significantly elevated the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT, p < 0.05). However, subsequent treatment with SAGE-IFO significantly reduced the activity of these liver enzymes (p < 0.05). The concentration of reduced glutathione (GSH) as well as the activities of catalase and glutathione reductase (GR) significantly increased, while malondialdehyde (MDA) level decreased significantly in SAGE-IFO group, when compared with free-IFO group (p < 0.05). Treatment with SAGE-IFO significantly restored white blood cell (WBC) count and platelet levels which were altered by free-IFO (p < 0.05). Conclusion: The results obtained in this study suggest that loading IFO in sage oil-NE greatly reduces its hepatotoxicity and hematotoxicity

Antitumor activity of doxorubicine-loaded nanoemulsion against Ehrlich ascites carcinoma-bearing mice

Purpose: To evaluate the antitumor activity of doxorubicine (DOX) loaded nanoemulsion (NE) on Ehrlich ascites carcinoma (EAC)-bearing Swiss albino mice.Methods: The mice were divided into five groups (n = 20) according to the administered drug. Groups I - V were labeled as negative control (normal), positive control of the untreated EAC bearing mice (EAC control), blank nanoemulsion (BI-NE), DOX-loaded-NE (DOX/LNE) and free DOX (DOX-Sol), respectively. Cardiotoxicity was assessed by measuring changes in body and organ weight, analyzing serum enzymes and lipids, and examining histological changes in heart tissues by light microscopy. In addition, mean survival time (MST), increase in life span (ILS) and survival (S) of the mice were determined.Results: DOX/LNE group reduced levels of serum enzymes and lowered damage to heart tissues relative to DOX-Sol group. The MST of the DOX/LNE group (80 ± 0.0 days) was significantly greater than that for DOX-Sol group (34.6 ± 8.9 days), while ILS of DOX/LNE (265.30 days) was higher than that of DOX-Sol (57.99 days) by 4.6-fold.Conclusion: Administration of DOX/LNE to EAC-bearing mice improves the efficacy of DOX and reduce its side effects on the heart.Keywords: Doxorubicine, Anti-tumor activity, Mean survival time, Heart histology, Nanoemulsion, Lipid profil

Antihyperglycemic Potential of Grewia asiatica Fruit Extract against Streptozotocin-Induced Hyperglycemia in Rats: Anti-Inflammatory and Antioxidant Mechanisms

Diabetes mellitus is regarded as a serious chronic disease that carries a high risk for considerable complications. In folk medicine, the edible Grewia asiatica fruit is used in a number of pathological conditions. This study aimed to investigate the possible curative effect of G. asiatica fruit ethanolic extract against streptozotocin- (STZ-) induced hyperglycemia in rats. Furthermore, mechanism of antihyperglycemic action is investigated. Hyperglycemic rats are either treated with 100 or 200 mg/kg/day G. asiatica fruits extract. Serum glucose, liver glycogen, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), interleukin- (IL-) 1β, and tumor necrosis factor- (TNF-) α are measured. G. asiatica fruits extract reduces blood glucose and pancreatic MDA levels. It increases liver glycogen and pancreatic GSH contents and SOD enzyme activity. Furthermore, Grewia asiatica fruits extract decreases serum IL-1β and TNF-α. The treatment also protects against STZ-induced pathological changes in the pancreas. The results of this study indicated that G. asiatica fruit extract exerts antihyperglycemic activity against STZ-induced hyperglycemia. The improvement in the pancreatic β-cells and antioxidant and anti-inflammatory effects of G. asiatica fruit extract may explain the antihyperglycemic effect

Design, synthesis, molecular docking, and in vitro studies of 2-mercaptoquinazolin-4(3H)-ones as potential anti-breast cancer agents

Triple-negative breast cancer (TNBC) comprises 10 % to 20 % of breast cancer, however, it is more dangerous than other types of breast cancer, because it lacks druggable targets, such as the estrogen receptors (ER) and the progesterone receptor (PR), and has under expressed receptor tyrosine kinase, ErbB2. Present targeted therapies are not very effective and other choices include invasive procedures like surgery or less invasive ones like radiotherapy and chemotherapy. This study investigated the potential anticancer activity of some novel quinazolinone derivatives that were designed on the structural framework of two approved anticancer drugs, Ispinesib (KSP inhibitor) and Idelalisib (PI3Kδ inhibitor), to find out solutions for TNBC. All the designed derivatives (3a-l) were subjected to extra precision molecular docking and were synthesized and spectrally characterized. In vitro enzyme inhibition assay of compounds (3a, 3b, 3e, 3 g and 3 h) revealed their nanomolar inhibitory potential against the anticancer targets, KSP and PI3Kδ. Using MTT assay, the cytotoxic potential of compounds 3a, 3b and 3e were found highest against MDA-MB-231 cells with an IC50 of 14.51 µM, 16.27 µM, and 9.97 µM, respectively. Remarkably, these compounds were recorded safe against the oral epithelial normal cells with an IC50 values of 293.60 µM, 261.43 µM, and 222 µM, respectively. The anticancer potential of these compounds against MDA-MB-231 cells was revealed to be associated with their apoptotic activity. This was established by examination with the inverted microscope that revealed the appearance of various apoptotic features like cell shrinkage, apoptotic bodies, and membrane blebbing. Using flow cytometry, the Annexin V/PI-stained cancer cells showed an increase in early and late apoptotic cells. In addition, DNA fragmentation was revealed to occur after treatment with the tested compounds by gel electrophoresis. The relative gene expression of pro-apoptotic and anti-apoptotic genes revealed an overexpression of the P53 and BAX genes and a downregulation of the BCL-2 gene by real-time PCR. So, this work proved that compounds 3a, 3b, and 3e could be developed as anticancer candidates, via their P53-dependent apoptotic activity