An in vitro cytotoxicity of glufosfamide in HepG2 cells relative to its nonconjugated counterpart.

Background: Glufosfamide (β-D-glucosylisophosphoramide mustard, GLU) is an alkylating cytotoxic agent in which ifosforamide mustard (IPM) is glycosidically linked to the β-D-glucose molecule. GLU exerted its cytotoxic effect as a targeted chemotherapy. Although, its cytotoxic efficacy in a number of cell lines, there were no experimental or clinical data available on the oncolytic effect of oxazaphosphorine drugs in hepatocellular carcinoma.

Therapeutic effects of thymoquinone or capsaicin on acrylamide-induced reproductive toxicity in rats mediated by their effect on oxidative stress, inflammation, and tight junction integrity.

In the field of environmental toxicology, endocrine-disrupting effects have become a major concern. The present research set out to investigate the possible reproductive toxicity of acrylamide. The research was also expanded to explore the protective effects of two nutraceuticals, thymoquinone (TQ) and capsaicin, against acrylamide-induced reproductive toxicity.

L-carnitine extenuates endocrine disruption, inflammatory burst and oxidative stress in carbendazim-challenged male rats via upregulation of testicular StAR and FABP9, and downregulation of P38-MAPK pathways.

We have addressed in the current study the potential of L-carnitine (LC) to extenuate the reproductive toxic insults of carbendazim (CBZ) in male rats, and the molecular mechanisms whereby carnitine would modify the spermatogenic and steroidogenic derangements invoked by the endocrine disruptor. Herein, animals received daily doses of carbendazim (100 mg/kg) by gavage for 8 weeks. Another CBZ-challenged group was co-supplemented with LC (500 mg/kg, IP) twice weekly for 8 weeks.

Possible protective effect of TNF-α inhibition and triad NO/cGMP/VEGF activation on gastric ulcer in rats.

Peptic ulcers are one of the world's major gastrointestinal disorders, embracing both gastric and duodenal ulcers, and affecting 10% of the world population. The current study aimed to investigate the possible protective effect of tadalafil and pentoxifylline (PTX) on indomethacin-induced peptic ulcers. Male albino rats were divided into five groups: control group; ulcerated group; Indomethacin + Tadalafil, in which animals were pretreated with tadalafil orally before indomethacin; Indomethacin+ PTX, in which animals were pretreated with PTX orally before indomethacin; and Indomethacin + Tadafil + PTX.

The chemomodulatory effects of glufosfamide on docetaxel cytotoxicity in prostate cancer cells.

Background. Glufosfamide (GLU) is a glucose conjugate of ifosfamide in which isophosphoramide mustard is glycosidically linked to the β-D-glucose molecule. Based on GLU structure, it is considered a targeted chemotherapy with fewer side effects.

Possible contribution of beta-glucosidase and caspases in the cytotoxicity of glufosfamide in colon cancer cells.

Glycoconjugates represent a recent trend in cancer chemotherapy that adopts the concept of selective prodrug/drug targeting of tumor cells by binding to specific transmembrane glucose transporters. Following preferential uptake of sugar conjugates into cancer cells, they are presumably subject to enzymatic cleavage by specific beta-glycosidases to liberate the free active cytotoxic aglycones that act selectively on cancer cells and spare other noncancerous ones. In this sense, the role of beta-glucosidase and caspases in the bioactivation and cytotoxicity of glufosfamide has been addressed in the current study.

Possible contribution of beta-glycosidases and caspases in the cytotoxicity of novel glycoconjugates in colon cancer cells.

Glycoconjugates represent a recent trend in cancer chemotherapy that adopts the concept of selective prodrug/drug targeting of tumor cells by selectively binding to specific transmembrane glucose transporters. Following preferential uptake of sugar conjugates into cancer cells, they are presumably subject to enzymatic cleavage by specific beta-glycosidases to liberate the free active cytotoxic aglycones that act selectively on cancer cells and spare other noncancerous ones. In this sense, the cytotoxicity of an array of newly synthesized glycoconjugates, including curcumin beta-glucoside, perillyl alcohol beta-glucoside, perillyl alcohol beta-galactoside, diethylstilbesterol beta-glucoside and diethylstilbesterol beta-galactoside have been investigated over 24-96 h in a panel of human colon cancer cells namely, Caco-2, HT29 and T84 cells.

Uroprotective effects of curcumin in cyclophosphamide-induced haemorrhagic cystitis paradigm.

The possible uroprotective effects of curcumin have been addressed in the current study. Haemorrhagic cystitis was induced by challenging male Swiss albino rats with a single dose of cyclophosphamide (150 mg/kg, i.p.

Acetyl-L-carnitine ameliorates caerulein-induced acute pancreatitis in rats.

In the present study, we have addressed the possible protective role of acetyl-L-carnitine in caerulein-induced acute pancreatitis in male Swiss albino rats. Acute pancreatitis paradigm was developed by challenging animals with a supramaximal dose of caerulein (20 microg/kg, SC) four times at hourly intervals. Caerulein induced acute pancreatitis that was well-characterized morphologically and biochemically.

Prophylactic role of curcumin in dextran sulfate sodium (DSS)-induced ulcerative colitis murine model.

We have addressed in this study the possible protective role of the main principle of turmeric pigment; curcumin on a murine model of ulcerative colitis (UC). Colitis was induced by administration of dextran sulfate sodium (DSS) (3% W/V) in drinking water to male Swiss albino rats for 5 consecutive days. DSS challenge induced UC model that was well characterized morphologically and biochemically.

Gene therapy targeting leiomyoma: adenovirus-mediated delivery of dominant-negative estrogen receptor gene shrinks uterine tumors in Eker rat model.

Objective: To evaluate the utility of gene therapy for uterine fibroids in the Eker rat model using an adenovirus-mediated delivery of a dominant-negative estrogen receptor gene (Ad-DNER).

Design: Animal study.

Setting: University animal laboratory.

Carnitine deficiency aggravates carboplatin nephropathy through deterioration of energy status, oxidant/anti-oxidant balance, and inflammatory endocoids.

We have recently shown that carnitine deficiency could represent a risk factor in paracetamol hepatotoxicity. By the same token, d-carnitine-induced carnitine deficiency aggravated carboplatin nephropathy following challenge with a single dose (35mg/kg, IP) of the platinum drug in male Swiss albino rats. The combination modality induced marked degenerative changes and severe inflammation in kidney tissues that surpassed either carboplatin or d-carnitine given alone.

Carnitine deficiency: a possible risk factor in paracetamol hepatotoxicity.

We have addressed in the current study the postulate whether or not carnitine deficiency would represent a risk factor in hepatotoxicity. Carnitine-deficient male Swiss albino rats were obtained following administration of D-carnitine (500 mg/kg, IP) for 10 consecutive days. Serum and liver carnitine levels, both total and free, were assessed to confirm carnitine depletion.

Memy I: a novel murine model for uterine leiomyoma using adenovirus-enhanced human fibroid explants in severe combined immune deficiency mice.

Objective: This study was undertaken to develop a representative murine model for human leiomyoma.

Study Design: Human fibroid tumor tissues were cut into small pieces and treated with medium alone, adenoviral-beta-galactosidase, adenoviral-vascular endothelial growth factor-A, adenoviral-cyclooxygenase-2, or both adenoviral-vascular endothelial growth factor-A and adenoviral- cyclooxygenase-2. Tissue pieces were inserted subcutaneously in the flank of each severe combined immunodeficient mouse.

Adenovirus-mediated delivery of a dominant-negative estrogen receptor gene in uterine leiomyoma cells abrogates estrogen- and progesterone-regulated gene expression.

Context: Human uterine leiomyomas are very common smooth muscle cell tumors that occur in reproductive-age women and are the leading reason for performing hysterectomies. The present study was conducted to explore the potential mechanism behind the effects exerted by dominant-negative estrogen receptors (DNERs) delivered by adenovirus to leiomyoma cells to ascertain the utility of DNERs as a novel strategy for treatment of uterine fibroids.

Objective And Methods: We investigated the ability of DNER to affect estrogen response element (ERE) activity induced by wild-type estrogen receptor (ER) by using the adenovirus ERE luciferase (Ad-ERE-luc) system in ELT3 cells and the effect of graded doses of DNER (10, 50, and 100 plaque-forming units/cell) on the expression of some selected genes controlling cultured human leiomyoma cell proliferation (cyclin D1, Cox2, PCNA, VEGF, and EGF), apoptosis (Bcl2 and Bax), estrogen metabolism (COMT), and extracellular matrix formation (MMP(1)) as well as progesterone receptors (A and B) were assessed using Western blot analysis.

Anti-fibrotic effect of meloxicam in a murine lung fibrosis model.

A murine lung fibrosis model has been induced by challenging male Swiss albino mice with a fibrotic dose of bleomycin (10 mg/kg body weight, s.c.) twice weekly for 6 weeks.

Enhancement by dexamethasone of the therapeutic benefits of cisplatin via regulation of tumor angiogenesis and cell cycle kinetics in a murine tumor paradigm.

We have investigated in the current study, the possible modulatory effects of dexamethasone on cisplatin cytotoxicity in Ehrlich ascites carcinoma (EAC)-bearing female Swiss albino mice. Cisplatin (3.5mg/kg) was injected IP for 3 consecutive days in mice previously inoculated SC with EAC cells in the right flank.

Neuroprotective effect of taurine in 3-nitropropionic acid-induced experimental animal model of Huntington's disease phenotype.

An experimental animal model of Huntington's disease (HD) phenotype was induced using the mycotoxin 3-nitropropionic acid (3-NP) and was well characterized behaviorally, neurochemically, morphometrically and histologically. Administration of 3-NP caused a reduction in prepulse inhibition (PPI) of acoustic startle response, locomotor hyper- and/or hypoactivity, bilateral striatal lesions, brain oxidative stress, and decreased striatal gamma-aminobutyric acid (GABA) levels. Taurine is a semi-essential beta-amino acid that was demonstrated to have both antioxidant and GABA-A agonistic activity.

Curcumin attenuates diet-induced hypercholesterolemia in rats.

Background: Curcumin (a component of turmeric) has long been used as a spice and food-coloring agent. In experimental animals, curcumin has shown anti-diabetic, anti-inflammatory, cytotoxic and anti-oxidant properties.

Material/methods: The possible hypolipidemic effect of curcumin was investigated in rats fed a high-cholesterol diet (HCD).

Protective role of carnitine esters against alcohol-induced gastric lesions in rats.

We have investigated in the current study the possible protective effects of two carnitine esters known to have powerful anti-oxidant potential namely, propionyl L-carnitine (PLC) and acetyl L-carnitine (AC) against alcohol-induced gastric lesions in rats. Both drugs were administered as a single oral dose of 200 mg kg(-1) body weight 1h before alcohol intake. Both carnitine esters could protect the gastric mucosa against the injurious effect of absolute alcohol and promote ulcer healing as evidenced from the ulcer index (UI) values.

Immunomodulatory effects of L-carnitine and q10 in mouse spleen exposed to low-frequency high-intensity magnetic field.

In the current study, we have investigated the bioeffects of repeated exposure to low-frequency (50 Hz) high-intensity (20 mT; 200 G) electromagnetic field (EMF) on some immune parameters in mice. The animals were exposed to EMF daily for 30 min three times per week for 2 weeks. We also studied the possible immunomodulatory effects of two anti-radical substances known to have non-specific immunostimulant effects namely, L-carnitine (200 mg/kg body weight i.

Potential protective effect of melatonin against dibromoacetonitrile-induced oxidative stress in mouse stomach.

Dibromoacetonitrile (DBAN) is a disinfection by-product following chlorination of drinking water. Epidemiological studies indicate that it might present a potential hazard to human health. DBAN was previously found to induce oxidative stress in rat stomach as manifested by perturbation of some enzymatic and nonenzymatic antioxidant parameters.