mohammad sharif talebianpoor

Preeclampsia is the principal cause of maternal morbidity and is characterized by hypertension, proteinuria, and edema. It is believed that oxidative stress plays an essential role in the pathophysiology of preeclampsia. This study was conducted to determine the effect of tempol on fetal limb hemorrhage, malformations, and oxidative stress in an N-nitro-L-arginine methyl ester (L-NAME)-induced preeclamptic rat model.

To induce preeclampsia, L-NAME (50 mg/kg/day, oral) was administered from day 11 of pregnancy to day 22. Four preeclamptic groups received L-NAME alone, L-NAME+tempol (20, 60, 180 mg/kg/day; L-NAME, L-T20, L-T60, L-T180 groups, respectively). The control group (normal pregnant) received only tap water, and the T60 group received tempol (60 mg/Kg) alone (without L-NAME). The concentration of 8-isoprostane in plasma and placenta, number and weight of the fetuses, and the limb defects were measured on the 22nd day of the pregnancy.

L-NAME administration caused placental oxidative stress, limb defects and hemorrhage, and low fetal weight. Administration of tempol at 20 and 60 mg/kg/day reduced limb defects (10.5 and 7.2 percent versus 24.7 percent) and limb hemorrhage (14.5 and 9.5 percent versus 23 percent) induced by L-NAME. After administration of tempol (20 and 60 mg/kg), fetal weight increased (5.14±0.08 and 5.44±0.15 versus 4.27± 0.11 g). Administration of tempol at the high dose (180 mg/kg/day) did not produce any significant effects on the measured parameters.

Tempol with certain doses improves fetal outcomes in an experimental rat model of preeclampsia. These may be the results of its antioxidant action.

Regarding to the important role of Staphylococcus aureus in burn wound infection, the aim of the present study were to investigation of the effect of Polycaprolactone (PCL) scaffold with Myrtus communis extract on the healing of burn wound infections induced by Methicillin-resistant Staphylococcus aureus in rats.

In this experimental study, 42 male Wistar rats were divided into 7 equal groups. Second-degree burns developed on the backs of all animals after anesthesia by injection of a mixture of ketamine and xylazine, and then MRSA was inoculated uniformly on the wounds of all mice. Burn wounds were treated daily with Polycaprolactone (PCL) scaffold, PCL- myrtus 1%, PCL- myrtus 0.5%, PCL-silver sulfadiazine and PCL-Myrtus-silver sulfadiazine ointments. We investigated the antimicrobial properties, wound healing percentage, wound area, malondialdehyde and nitric oxide concentrations of rats. Data analysis was performed using GRAPH PAD software and One-way Anova and Tukey tests

Histopathological observations showed that PCL- myrtus group had wound healing properties in comparison with control group (p<0.05). PCL- myrtus group had reduced bacterial growth compared to PCL group and positive control group. Also biochemical tests showed a decrease in malondialdehyde and nitric oxide in rats treated with the PCL-Myrtus ointment compared to the other groups.

According to the results PCL containing myrtus ointment have an important role on accelerate the healing process, reducing time for wound healing and prevention of infection caused by MRSA.

Podophyllotoxin is used as one of the main treatments for genital warts. It is a precursor of etoposide and teniposide, which is used in the treatment of various cancers. Despite a large number of cancer studies, the exact mechanism of podophyllotoxin remains unknown. Chemotherapy drugs reduce cancer cells by inducing apoptosis. The regulation of the apoptotic pathway has been extensively studied in pharmaceutical research. The process of induction of apoptosis is performed by caspases. Suppression of enzymatic activity of adult caspases occurs in cancer cells in the presence of specific members of the IAPs family such as XIAP, cIAP1, and Survivin. By specifically binding Smac-mimetics to negative apoptosis regulators, inhibition of IAPs-mediated caspases is eliminated and apoptosis is induced. The development of Smac-mimetics as new anticancer drugs has been targeted. In the present study, bioinformatics was used to investigate the mechanism of action of podophyllotoxin as a Smac-mimetics on possible important routes of apoptosis.

Molecular docking method was used to calculate the molecular interaction of podophyllotoxin with proteins associated with initiator and effector caspases including XIAP / cAIP1-BIR3 and Survivin, as well as Bcl-2 and EGFR. The theoretical binding site of podophyllotoxin on these anti-apoptotic proteins was determined as an inhibitor to obtain information on the initial interaction, free binding energy and inhibition constant by molecular docking method.

The proapoptotic activity of podophyllotoxin as an apoptotic-inducing agent is associated with the signaling pathways of caspases 3, 7, 8, and 9. The key activation mechanisms of these caspases may be due to podophyllotoxin binding and induction of conformational changes at active sites of the XIAP / cAIP1-BIR3 and Survivin located near or at the same Smac-mimetics binding site. Three strong hydrogen bonds with the amino acids Tyr108, Ser117 and Glu118 play important roles in the stabilization of the Bcl-2-podophyllotoxin complex. Podophyllotoxin, similar to EGFR inhibitors, forms several hydrophobic interactions and two strong hydrogen bonds with Thr830 and Met769 with a bond-free energy of -7.85 kcal / mol and an inhibition constant of Ki = 1.76 µM.

Induction of apoptosis in cancer cells by podophyllotoxin can be attributed to several different mechanisms. Predicted binding conformations showed that podophyllotoxin had valuable inhibitory potential. Therefore, podophyllotoxin may be considered as an effective anticancer agent for further research into drug development.

The present study was conducted to evaluate the effect of curcumin as a flavonoid antioxidant on serum lipid profile, oxidative stress, and blood glucose in experimental models of type 2 diabetes (DM2).

Subcutaneous daily injection of dexamethasone (5 mg/kg/day) for a month was performed to induce DM2. For this purpose, 28 adult male Wistar rats were divided into four groups: healthy control group received dexamethasone carrier containing normal saline + ethanol 4% , diabetic control group took 5 mg/kg/day dexamethasone, diabetic group 1 underwent the treatment with 50 mg/kg/day curcumin, and diabetic group 2 underwent treatment with 100 mg/kg/day curcumin. Seven days after dexamethasone injection, curcumin (50 and 100 mg/kg/day) was administrated intraperitoneally for 23 days. At the end of one month, the fasting blood sugar (FBS) level was measured and recorded by glucometer. Later, after a 30-day period, the animals were anesthetized with ether and their blood samples were collected from the heart puncture to measure their serum triglyceride (TG), high density lipoprotein cholrsterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and malondialdehyde (MDA).

The findings showed that curcumin could decrease FBS (P < 0.05), LDL-C (P < 0.01), TG (P < 0.001), and MDA (P < 0.001) and increase HDL-C (P < 0.001)  at the end of 30 days.

These effects of curcumin can be mediated by increasing either the pancreatic secretion of insulin or releasing from insulin bonds as well as enhancing insulin receptor sensitivity. Moreover, it may prevent the glucose absorption, reduce the activity of 3-hydroxy- 3-methyl glutaryl- CoA reductase (HMG-CoA), or improve the function of liver and pancreas through potent antioxidant properties.

It has been suggested that oxidative stress has a crucial role in the pathophysiology of preeclampsia. In the present study, the effect of tempol, a synthetic antioxidant, on kidney injuries and oxidative stress was investigated in an experimental model of preeclampsia in rats.
Preeclampsia was induced by oral administration of L-NAME to the rats on the day 10 of pregnancy. Animals were randomly divided into six groups (10-15 rats in each group); (I) normal pregnant (II) preeclamptic (III, IV, V) preeclamptic tempol 20, 60 and 180 mg/kg/day, respectively, (VI) preeclamptic hydralazine 10 mg/kg/day. Urine levels of sodium, potassium, creatinine, lactate dehydrogenase and 24 h protein, blood levels of creatinine and urea, in addition to malondialdehyde concentration in blood and kidney, as well as histological glomeruli changes were assessed.
L-NAME administration caused proteinuria and glomerular pathological changes. Tempol (20 and 60 mg/kg/day) significantly reduced plasma and renal (P Renal complications of experimental preeclampsia such as proteinuria and glomerular injuries can be prevented by tempol. The desired effects of tempol depend on its dose.

To evaluate the hepatoprotective properties of Otostegia persica (O. persica) ethanol extract on carbon tetrachlo­­ride-induced liver damage in rats. Fifty adult male Wistar rats were randomly divided into five groups. Group I served as normal control and was given only olive oil intraperitoneally (i.p.). Group II, III, IV, and V were administered CCl4 mixed with olive oil 1:1 (1 ml/kg) i.p., twice a week for 8 weeks. Group II was maintained as CCl4-intoxicated control (hepatotoxic group). Group III, IV, and V received O. persica extract at a dose of 40, 80, and 120 mg/kg for 8 weeks every 48 h orally, respectively. Biochemical parameters including aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TB), albumin (ALB), total protein (TP), and lipid peroxidation marker (Malonaldialdehyde, (MDA) were determined in serum. After 8 weeks, animals were sacrificed, livers dissected out, and evaluated for histomorphological changes. The administration of CCl4 increased AST, ALT, ALP, TB, and MDA in serum but it decreased TP, and ALB compared with normal control. Treatment with O. persica extract at three doses resulted in decreased enzyme markers, bilirubin levels, and lipid peroxidation marker (MDA) and increased TP and ALB compared with CCl4 group. The results of pathological study also support the hepatoprotective effects which were observed at doses of 80 and 120 mg/kg. The results of the present study indicate that ethanol extract of O. persica may have hepatoprotective effect which is probably due to its antioxidant property.