scholarly journals Modulation of c-Fos and BDNF Protein Expression in Pentylenetetrazole-Kindled Mice following the Treatment with Novel Antiepileptic Compound HHL-6

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Saima Mahmood Malhi ◽  
Huma Jawed ◽  
Farina Hanif ◽  
Nadeem Ashraf ◽  
Farhat Zubair ◽  
...  

Brain-derived neurotrophic factor (BDNF) and c-Fos are shown to promote epileptogenesis and are taken as a marker of neuronal activity. The present study investigated the expression of BDNF and c-Fos in mice brain with pentylenetetrazol- (PTZ-) induced generalized seizure and evaluated the effect of novel tryptamine derivative HHL-6 on the expression of these two markers. The subconvulsive dose of PTZ (50 mg/kg) was administered on alternate days in the experimental groups until the seizure scores 4-5 developed in the PTZ-control group. At the end of each experiment, animals were sacrificed, brain samples were collected and cryosectioned, and immunohistochemical analysis of BDNF and c-Fos protein was performed. Data obtained from two sections per mouse (n=12animals/group) is presented as means ± S.E.M. The test compound HHL-6 demonstrated a potent anticonvulsant activity in the PTZ-induced seizure in mice. Significant reduction in the BDNF (P<0.003) and c-Fos (P<0.01) protein expression was observed in the HHL-6 treated group. Based on these results we suggest that one of the possible mechanisms of HHL-6 to inhibit epileptogenesis might be due to its controlling effect on the cellular and molecular expression of the factors that contribute to the development of epileptogenic plasticity in the CNS.

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Leilei Zhou ◽  
Chunju Xue ◽  
Zongyu Chen ◽  
Wenqing Jiang ◽  
Shuang He ◽  
...  

Abstract Background As one of the basic treatments performed in the intensive care unit, mechanical ventilation can cause ventilator-induced acute lung injury (VILI). The typical features of VILI are an uncontrolled inflammatory response and impaired lung barrier function; however, its pathogenesis is not fully understood, and c-Fos protein is activated under mechanical stress. c-Fos/activating protein-1 (AP-1) plays a role by binding to AP-1 within the promoter region, which promotes inflammation and apoptosis. T-5224 is a specific inhibitor of c-Fos/AP-1, that controls the gene expression of many proinflammatory cytokines. This study investigated whether T-5224 attenuates VILI in rats by inhibiting inflammation and apoptosis. Methods The SD rats were divided into six groups: a control group, low tidal volume group, high tidal volume group, DMSO group, T-5224 group (low concentration), and T-5224 group (high concentration). After 3 h, the pathological damage, c-Fos protein expression, inflammatory reaction and apoptosis degree of lung tissue in each group were detected. Results c-Fos protein expression was increased within the lung tissue of VILI rats, and the pathological damage degree, inflammatory reaction and apoptosis in the lung tissue of VILI rats were significantly increased; T-5224 inhibited c-Fos protein expression in lung tissues, and T-5224 inhibit the inflammatory reaction and apoptosis of lung tissue by regulating the Fas/Fasl pathway. Conclusions c-Fos is a regulatory factor during ventilator-induced acute lung injury, and the inhibition of its expression has a protective effect. Which is associated with the antiinflammatory and antiapoptotic effects of T-5224.


Author(s):  
BIPUL RAY ◽  
KAMSAGARA LINGANNA KRISHNA

Objectives: The objectives of the present investigation were to evaluate the memory impairment (MI) activity of eslicarbazepine (ESL) in temporal lobe epilepsy (TLE) at a normal and reduced dose, to evaluate the possible protective effect of nefiracetam (NEF) on MI induced by ESL at a normal and reduced dose, and to evaluate the antiepileptic activity of ESL on TLE in the presence and absence of NEF. Methods: MI activity was evaluated by Barnes maze (BM) on lithium-pilocarpine-induced TLE in Wistar albino rats. Rats were trained by releasing from the portable start-up box after keeping sometimes inside, to find the fixed dark escape hole of BM. Mild aversive light overhead was used to motivate the finding. Animals failed to do so were guided manually. Trained animals were taken for the study and checked the escape latency time (ELT) and the error scores (error entry). The treatment was given for 1 month and MI activity was measured on every 7th day and antiepileptic activity on every 8th day. Phenytoin was used as standard antiepileptic drug (AED) to compare the MI extent of ESL. Results: ESL-treated group animals had shown increased ELT and error scores, on comparison with control group, implying the MI as a result treatment of the AED ESL. MI was dose dependent and shown decreased MI in animals treated with half dose of ESL. When NEF was administered with the ESL significantly decreased the MI as well as showed potent anticonvulsant activity when compared to control and ESL alone treated group. The levels of acetylcholinesterase (AChE) in ESL group were observed to be increased against control group. Cotreatment of NEF results in decreased levels of AChE on comparison with control and the group treated with ESL. Conclusion: The reduced dose of ESL and NEF combination was found to have synergized the protecting effect against MI compared to normal ESL and NEF group without altering anticonvulsant activity. However, further studies are required to elicit detailed protective activity of NEF on MI induced by ESL.


Author(s):  
AZMAN ABDULLAH ◽  
NADIA SALEM ALRAWAIQ ◽  
AHMED ATIA

Objective: Heme oxygenase-1 (HO-1) is enzyme that possesses antioxidant, anti-inflammatory, and cytoprotective functions. Induction of HO-1 occurs as an adaptive and beneficial response to various injurious stimuli such as oxidative stress. This study is aimed at monitoring the effects of administration of equal doses (50 mg/kg) of sulforaphane (SFN), curcumin, quercetin, indole-3-carbinol, and butylated hydroxyanisole (BHA) for 14 days on the levels of liver HO-1 gene and protein expression in mice. Method: A total of 48 adult male ICR white mice (25–30 g) were divided into eight groups: Normal control group (n=6), SFN-treated group (n=6), quercetin-treated group (n=6), curcumin-treated group (n=6), BHA-treated group (n=6), indole-3-carbinol treated group (n=6), vehicle 1 control group (n=6), and vehicle 2 control group (n=6). All chemicals were administered intraperitoneally at a dose of 50 mg/kg for 14 days. Vehicle 1 (dimethyl sulfoxide, TweenTM 20, and normal saline at a ratio of 0.05:0.1:0.85) was used to dissolve SFN, quercetin, and curcumin. Vehicle 2 (corn oil) was used to dissolve indole-3-carbinol and BHA. At day 15, the animals were sacrificed and their livers were isolated. From the liver, total RNA was extracted, reverse transcribed and subjected to quantitative real‐time polymerase chain reaction to detect HO-1 gene expression. Agarose gel electrophoresis was also performed to verify the specificity of the amplification. HO-1 protein expression was determined by Western blotting. Results: HO-1 gene expression showed significant increase of 4.6±0.3, 3.6±0.2, 3.6±0.4, 3.3±0.3, and 3.0±0.4-fold and HO-1 protein expression showed significant increase of 2.3±0.2, 2.2±0.2, 2.2±0.1, 1.8±0.1, and 1.7±0.2-fold following treatment with 50 mg/kg of SFN, indole-3-carbinol, BHA, curcumin, and quercetin, respectively, compared to controls (p<0.05). Conclusion: At a dose of 50 mg/kg, SFN administration for 14 days resulted in the highest induction of HO-1 gene and protein expression level in mice liver, and quercetin the lowest.


2006 ◽  
Vol 76 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Yukari Egashira ◽  
Shin Nagaki ◽  
Hiroo Sanada

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidneyα-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.


1981 ◽  
Vol 45 (03) ◽  
pp. 276-281 ◽  
Author(s):  
S Ishimaru ◽  
E Berglin ◽  
H-A Hansson ◽  
A-C Teger-Nilsson ◽  
G William-Olsson

SummaryA segment of the inferior vena cava was replaced by an expanded polytetrafluoroethylene graft in 13 dogs. Five of them served as a control group, while the other 8 were moderately or severely defibrinogenated with subcutaneous batroxobin. Plasma fibrinogen decreased to extremely low values throughout the experiment in the defibrinogenated dogs except in the moderately treated group in which it temporarily rose to 0.72-0.87 g/1 on the first postoperative day.Scanning electron microscopic observations of the haemostatic clot formed at the anastomoses of the graft revealed no significant morphological differences in platelet adhesion and/or aggregation between the three groups. These findings confirmed that platelets play a key role in primary haemostasis during defibrinogenation.The fibrin network was slightly diminished and only short fibrin filaments could be seen in the moderately and severely defibrinogenated groups respectively. These differences in composition of the clots are discussed in relation to their haemostatic capacity.


1981 ◽  
Vol 96 (2) ◽  
pp. 273-280 ◽  
Author(s):  
Mridula Chowdhury ◽  
Robert Tcholakian ◽  
Emil Steinberger

Abstract. It has been suggested that treatment of intact male rats with oestradiol benzoate (OeB) causes an interference with testosterone (T) production by the testes by a direct inhibitory effect on steroidogenesis. To test this hypothesis, different doses (5, 10 or 25 IU) of hCG were administered concomitantly with 50 μg of OeB to adult intact or hypophysectomized male rats. The testicular and plasma testosterone, and serum hCG levels were determined. The sex accessory weights were recorded. In the intact OeB-treated group of animals, hCG stimulated both the secondary sex organs and plasma testosterone levels above the intact control group. However, in hypophysectomized animals, although plasma testosterone levels increased above that of intact controls, their secondary sex organ weights did not. Moreover, inspite of high circulating hCG levels, the testicular testosterone content and concentration remained suppressed in OeB-treated animals. The reason for such dichotomy of hCG action on OeB-treated animals is not clear at present.


2020 ◽  
Vol 64 ◽  
pp. 123-128
Author(s):  
Jada Naga Lakshmi ◽  
A. Narendra Babu ◽  
Rama Rao Nadendla

Objectives: To evaluate anti-psoriatic activity of Phytochemicals on UV-Induced psoriasis in mouse tail model. Materials and Methods: Anti-psoriatic activity of selected phytochemicals on UV-Induced psoriasis in mouse tail model. The animals were dividing into 05 groups and each group contain 5 animals. Disease control group did not receive any treatment only exposure to UV-light, vehicle control treated with simple ointment, standard group treated with salicylic acid (1%w/w) ointment, remaining group are treated 1% and 2% selective phytochemical at two concentrations of ointment to topically on the tail skin. And the data were analysed using one way ANOVA followed by two-way ANOVA (Dunnett’s multiple comparisons test). Results: There was significant decrease in epidermal thickness (P < 0.05) as compared with control group. In 2% phytoconstituents has shown a significant reduction in the total epidermal thickness 8.4****±0.748, 7.6**±0.6781 and 8*±0.8366 in geraniol, glycyrrhizic acid and ellagic acid treated group, when compare to the disease induced animal, there was no lesion of Munro’s microabscess, capillary loop dilation along with elongation of rete ridges in the section of skin of rats. Psoriasis Severity Index was reduced in test treated groups as compared with that of disease control group. It was slowly reduced to 2nd week, totally (55-70%) reduction in PSI is observed at the time of third week of treatment period. Conclusion: The result of the study showed that the 2% of geraniol, ellagic acid, glycyrrhizicacid and hesperidin, exhibited significant activity on UV-induced psoriasis in rodents. The study implies that selected phytoconstituents are a promising research for further investigations to prove its anti-psoriatic activity.


Author(s):  
Ashraf Albrakati

Tramadol, a broadly in recent years, is an effective analgesic agent for the treatment of moderate to acute pain. Its metabolites are excreted by the kidney which may cause nephrotoxicity. Moringa oleifera leaves are commonly used to provide herbal and plant-derived medicinal products especially in developing nations. The present study was carried out to determine the biochemical and histopathological changes in the kidney of tramadol-treated albino mice and to evaluate the possible protective role of Moringa oleifera leaves against tramadol-induced nephrotoxicity. Twenty adult albino mice were divided into four groups. Control group (group i) received daily intraperitoneal injection of normal saline only, group ii received oral dose of Moringa oleifera leaves extract (20 mg/kg/bw) for three weeks, group iii received daily intraperitoneal dose of tramadol (0.3 mg/kg/bw) for the same period, group iv, received daily oral dose of Moringa oleifera leaves extract, (20 mg/kg/bw) three hours before injecting intraperitoneal dose of tramadol (0.3 mg/kg/bw), for the same period. Blood samples were withdrawn at the end of the experiment for kidney function tests and specimens from the kidney were processed for histological study. No significant differences in the mean values of the kidney function tests were noticed between Moringa oleifera group and control group. However, there was highly significant increase in the mean values of serum, urea and creatinine in tramadol-treated group as compared to the control group. Although tramadol + Moringa oleifera group revealed significant difference in the mean values of urea and creatinine when compared with tramadol-treated group. So, Moringa oleifera leaves extract have been shown to attenuate the renal dysfunction, improve the renal architecture, with nearly normalization of serum urea and creatinine levels which indicate improvement of renal function. In conclusion, in the light of biochemical results and histological findings, co-administration of Moringa oleifera leaves lessened the negative effects of tramadol-induced nephrotoxicity; possibly by its antioxidant action. Further investigation of these promising protective effects of Moringa oleifera leaves against tramadol-induced renal injury may have considerable impact on developing an adjunct therapy aiming to improve the therapeutic index of some nephrotoxic drugs.


Sign in / Sign up

Export Citation Format

Share Document