Effects of sex steroid hormones on neuromedin S and neuromedin U2 receptor expression following experimental traumatic brain injury

Objective(s): Neuroprotective effects of female gonadal steroids are mediated through several pathways involving multiple peptides and receptors after traumatic brain injury (TBI). Two of these peptides are including the regulatory peptides neuromedin U (NMU) and neuromedin S (NMS), and their common receptor neuromedin U2 receptor (NMUR2). This study investigates the effects of physiological doses of estradiol and progesterone on brain edema, NMS and NMU as well as NMUR2 expression following TBI. Materials and Methods: Ovariectomized female rats were given high-and low-dose of female sex steroid hormones through implantation of capsules for a week before trauma. The brain NMUR2 expression, prepro-NMS expression, NMU content, and water content (brain edema) were evaluated 24 hr after TBI induced by Marmarou’s method. Results: Percentage of brain water content in high- and low-dose estradiol, and in high- and low- dose progesterone was less than vehicle (

Cellular Preoxygenation Partially Attenuates the Antitumoral Effect of Cisplatin despite Highly Protective Effects on Renal Epithelial Cells

Our previous in vitro studies demonstrated that oxygen pretreatment significantly protects human embryonic renal tubular cell against acute cisplatin- (CP-) induced cytotoxicity. The present study was designed to investigate whether this protective effect is associated with decreasing therapeutic effects of cisplatin on malignant cells. For this purpose, cultured human embryonic kidney epithelial-like (AD293), cervical carcinoma epithelial-like (Hela), and ovarian adenocarcinoma epithelial-like (OVCAR-3) cells were subjected to either 2-hour pretreatment with oxygen (≥90%) or normal air and then to a previously determined 50% lethal dose of cisplatin for 24 hours. Cellular viability was evaluated via MTT and Neutral Red assays. Also, activated caspase-3 and Bax/Bcl-2 ratio, as the biochemical markers of cell apoptosis, were determined using immunoblotting. The hyperoxic preexposure protocol significantly protects renal AD293 cells against cisplatin-induced toxicity. Oxygen pretreatment also partially attenuated the cisplatin-induced cytotoxic effects on Hela and OVCAR-3 cells. However, it did not completely protect these cells against the therapeutic cytotoxic effects of cisplatin. In summary, the protective methods for reducing cisplatin nephrotoxic side effects like oxygen pretreatment might be associated with concurrent reduction of the therapeutic cytotoxic effects of cisplatin on malignant cells like cervical carcinoma (Hela) and ovarian adenocarcinoma (OVCAR-3) cells

Cellular Preoxygenation Partially Attenuates the Antitumoral Effect of Cisplatin despite Highly Protective Effects on Renal Epithelial Cells

Our previous in vitro studies demonstrated that oxygen pretreatment significantly protects human embryonic renal tubular cell against acute cisplatin-(CP-) induced cytotoxicity. The present study was designed to investigate whether this protective effect is associated with decreasing therapeutic effects of cisplatin on malignant cells. For this purpose, cultured human embryonic kidney epithelial-like (AD293), cervical carcinoma epithelial-like (Hela), and ovarian adenocarcinoma epithelial-like (OVCAR-3) cells were subjected to either 2-hour pretreatment with oxygen (≥90%) or normal air and then to a previously determined 50% lethal dose of cisplatin for 24 hours. Cellular viability was evaluated via MTT and Neutral Red assays. Also, activated caspase-3 and Bax/Bcl-2 ratio, as the biochemical markers of cell apoptosis, were determined using immunoblotting. The hyperoxic preexposure protocol significantly protects renal AD293 cells against cisplatin-induced toxicity. Oxygen pretreatment also partially attenuated the cisplatin-induced cytotoxic effects on Hela and OVCAR-3 cells. However, it did not completely protect these cells against the therapeutic cytotoxic effects of cisplatin. In summary, the protective methods for reducing cisplatin nephrotoxic side effects like oxygen pretreatment might be associated with concurrent reduction of the therapeutic cytotoxic effects of cisplatin on malignant cells like cervical carcinoma (Hela) and ovarian adenocarcinoma (OVCAR-3) cells

The Effect of Rosmarinus officinalis L Extract on the Inhibition of High Glucose-Induced Neurotoxicity in PC12 Cells: an In Vitro Model of Diabetic Neuropathy

Background and Aim: Diabetes mellitus and continued hyperglycemic condition prompt serious diabetic complications such as diabetic neuropathy. Numerous studies have shown the involvement of oxidative stress and high glucose-induced cell death in the progress of diabetic neuropathy. Rosmarinus officinalis L has been suggested in the literature as an anti-diabetic herbal medicine that contains potent antioxidant components. Therefore, the neuroprotective effect of Rosmarinus officinalis L (RE) extract was investigated in glucose-induced neurotoxicity via pheochromocytoma )PC12( cells as an appropriate in vitro model of diabetic neuropathy. Materials and Methods: Cell viability was determined using MTT assay. Cleave caspase-3 and Bax: Bcl2 ratio, as biochemical parameters of cellular apoptosis, were measured by western blotting analysis. Results: Our data showed that a 4-fold elevation in the medium glucose significantly reduced cell viability (P < 0.01) and increased caspase-3 activation (P < 0.01) as well as Bax: Bcl2 ratio (P < 0.05) in PC12 cells after 24 h. Incubation of high glucose medium cells with 60μg/ml RE extract decreased high glucose-induced cell toxicity and prevented caspase-3 activation and Bax: Bcl2 ratio. Conclusion: It could be concluded that RE extract is effective in the protection against hyperglycemia-induced cellular toxicity. This could be relevant to the prevention of apoptosis. Moreover, the results suggest that RE has the therapeutic potential to attenuate diabetes complications such as that neuropathy

Evaluation of Origanum Vulgare L. ssp. Viridis Leaves Extract Effect on Discrimination Learning and LTP Induction in the CA1 Region of the Rat Hippocampus

AbstractObjective(s)The objective of this study was to determine the effect of aqueous extract of Origanum vulgare L. ssp. Viridis (ORG) on discrimination learning and long term potentiation (LTP) in CA1 region of the rat hippocampus. Materials and MethodsA group of adult male Wistar rats weighing 27525 g received aqueous extract of ORG (150, 300, 450 mg/kg/day) by intraperitoneal injection for one week, and the other group received saline (n= 6). A wooden T-maze was used to evaluate the discrimination learning. In electrophysiological experiments, the effect of ORG leaves extract on induction and maintenance of long term potentiation (LTP) in CA1 hippocampus area was determined. LTP was evaluated in CA1 region after high-frequency stimulation (200 Hz) of the Schaffer collaterals. Also, serum antioxidant levels were analyzed in the two groups (n= 4).ResultsStatistical analysis showed significant decreases in the number of total (significantly at the dose of 300 and 450 mg/kg) and wrong (significantly at the dose of 300 mg/kg) entrance into opposite box of T-maze procedure in ORG-treated animals (P< 0.05). In electrophysiological study, the rats which had received ORG (150, 300, and 450 mg/kg) showed an increase in both population spike amplitude (59.7±14.1%, 85±14.7% and 49.3±8.7% respectively, compared to 39±9.2% increase in saline group) and maintenance of LTP in hippocampus CA1 after high frequency stimulation in Schaffer collateral pathway. In serum antioxidant assay, level of antioxidants in ORG groups (300 and 450 mg/kg) remarkably increased in comparison to saline group (P< 0.05 and P< 0.001, in turn).ConclusionOur results suggest that Origanum aqueous extract can improve the learning criteria in rats

Effects of CR on TGF-β1 level.

Data are expressed as mean ± SEM (n = 4 rats/group). ***PVS. Sham+SD; +++PVS. Sham+HFD; ##P#PVS. OVX+SD; &&&PVS. OVX+HFD; †PVS. Sham+SD+CR; ^PVS. Sham+HFD+CR. CR: Calorie restriction, HFD: High-fat diet, SD: Standard diet, Sham: Ovary-intact, OVX: Ovariectomy.</p

Comparison of CR effects on body weight changes, HW, HW/BW ratio, and LVW in Sham and OVX rats.

Comparison of CR effects on body weight changes, HW, HW/BW ratio, and LVW in Sham and OVX rats.</p

Effect of E2 administration on ANP mRNA expression in the LV of OVX animals.

Data are expressed as mean ± SEM (n = 4 hearts/group). ***PVS. SD+Oil; +++P+PVS. HFD+Oil; #PVS. SD+CR+Oil; &&&P&PVS. HFD+CR+Oil. CR: Calorie restriction, HFD: High-fat diet, SD: Standard diet, OVX: Ovariectomy, E2: 17-β estradiol, Oil: Sesame oil.</p

Effects of E2 treatment on body weight changes, HW, HW/BW ratio, and LVW in OVX rats.

Effects of E2 treatment on body weight changes, HW, HW/BW ratio, and LVW in OVX rats.</p