scholarly journals Targeting oxidative stress improves disease outcomes in a rat model of acquired epilepsy

Brain ◽  
2019 ◽  
Vol 142 (7) ◽  
pp. e39-e39 ◽  
Author(s):  
Alberto Pauletti ◽  
Gaetano Terrone ◽  
Tawfeeq Shekh-Ahmad ◽  
Alessia Salamone ◽  
Teresa Ravizza ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Status Epilepticus ◽  
Rat Model ◽  
Drug Combination ◽  
De Novo ◽  
Time Window ◽  
Therapeutic Effects ◽  
Drug Induced ◽  
Disease Outcomes ◽  
Acquired Epilepsy

AbstractEpilepsy therapy is based on antiseizure drugs that treat the symptom, seizures, rather than the disease and are ineffective in up to 30% of patients. There are no treatments for modifying the disease—preventing seizure onset, reducing severity or improving prognosis. Among the potential molecular targets for attaining these unmet therapeutic needs, we focused on oxidative stress since it is a pathophysiological process commonly occurring in experimental epileptogenesis and observed in human epilepsy. Using a rat model of acquired epilepsy induced by electrical status epilepticus, we show that oxidative stress occurs in both neurons and astrocytes during epileptogenesis, as assessed by measuring biochemical and histological markers. This evidence was validated in the hippocampus of humans who died following status epilepticus. Oxidative stress was reduced in animals undergoing epileptogenesis by a transient treatment with N-acetylcysteine and sulforaphane, which act to increase glutathione levels through complementary mechanisms. These antioxidant drugs are already used in humans for other therapeutic indications. This drug combination transiently administered for 2 weeks during epileptogenesis inhibited oxidative stress more efficiently than either drug alone. The drug combination significantly delayed the onset of epilepsy, blocked disease progression between 2 and 5 months post-status epilepticus and drastically reduced the frequency of spontaneous seizures measured at 5 months without modifying the average seizure duration or the incidence of epilepsy in animals. Treatment also decreased hippocampal neuron loss and rescued cognitive deficits. Oxidative stress during epileptogenesis was associated with de novo brain and blood generation of high mobility group box 1 (HMGB1), a neuroinflammatory molecule implicated in seizure mechanisms. Drug-induced reduction of oxidative stress prevented HMGB1 generation, thus highlighting a potential novel mechanism contributing to therapeutic effects. Our data show that targeting oxidative stress with clinically used drugs for a limited time window starting early after injury significantly improves long-term disease outcomes. This intervention may be considered for patients exposed to potential epileptogenic insults.

Cadmium acts as a silent killer of liver by inducing oxidative stress and hepatocellular injury and a possible amelioration by vitamin B12 and folic acid in rat model

2019 ◽  
Vol 1 ◽  
pp. 105-117
Author(s):  
A. Banerjee ◽  
P. Nandi ◽  
C. Bhattacharya ◽  
Z. Kabir ◽  
S. Mukherjee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Folic Acid ◽  
Vitamin B12 ◽  
Rat Model ◽  
Male Rats ◽  
Albino Rats ◽  
Therapeutic Effects ◽  
Hepatocellular Injury ◽  
Male Adult ◽  
Wistar Albino Rats

<br/><b>Purpose:</b> To investigate the involvement of oxidative stress in Cadmium (Cd) induced alteration in the functional status of the liver. And to assess the efficacy of folic acid and vitamin B12 in preventing Cd-induced damage in the same. <br/><b>Materials and methods:</b> The experiment was carried out for four weeks. For the experiment, 25 healthy male adult Wistar albino rats were randomly selected and were divided into five equal groups and treated as control, treated with Cd, supplemented with vitamin B12 and folic acid and in the combination of these two. After 28 days the liver function enzymes and oxidative stress parameters were measured. <br/><b>Results:</b> Cd is the silent killer of the hepatic system through the induction of oxidative stress in male rats. From this investigation, it is evident that the folic acid+vitamin B12 possess significant hepatoprotective and antioxidant activity against Cd-induced hepatotoxicity in the rat model. In addition, results revealed that the folic acid alone and or in combination with vitamin B12 blunted the hepatotoxic effect significantly. <br/><b>Conclusions:</b> Based on results obtained, it can be concluded that folic acid and vitamin B12 offer a protective effect in Cd-induced oxidative stress associated with hepatocellular injury. Folic acid and vitamin B12 can be considered as a potent natural antioxidant which has the capacity to provide protection against Cd-induced oxidative stress in the liver in rats. However, to elucidate the exact mechanism of this modulatory effect and to examine its potential therapeutic effects further studies are essential.

Characterisation of an infantile rat model of de novo status epilepticus: long-term outcomes

2019 ◽  
Vol 101 ◽  
pp. 106744
Author(s):  
Geatano Terrone ◽  
Rossella Di Sapia ◽  
Alessia Salamone ◽  
Ilaria Craparotta ◽  
Nosaibeh R. Zaniani ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Rat Model ◽  
De Novo ◽  
Long Term Outcomes

Neuroprotective effect of curcumin nanoparticles against rat model of status epilepticus induced by pilocarpine

2018 ◽  
Vol 15 (4) ◽  
Author(s):  
Yasser A. Khadrawy ◽  
Hussein G. Sawie ◽  
Eman N. Hosny
Keyword(s):  
Oxidative Stress ◽  
Status Epilepticus ◽  
Rat Model ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Brain Regions ◽  
Necrosis Factor Alpha ◽  
Curcumin Nanoparticles ◽  
Tnf Α ◽  
Factor Alpha

Abstract Background The present study aims to investigate the neuroprotective effect of curcumin nanoparticles (Cur-NP) on the rat model of status epilepticus (SE) induced by pilocarpine. Methods In the present study, animals were divided into three groups: control animals, rat model of SE induced by a single dose of pilocarpine (380 mg/kg) injected intraperitoneally, and rat model of SE that received a daily intraperitoneal injection of Cur-NP (50 mg/kg) for four consecutive days prior to pilocarpine administration. Results The present results revealed a state of oxidative stress in the cortex and hippocampus of rat model of SE as compared to control. This was evident from the significant increase in lipid peroxidation and the significant decrease in reduced glutathione and nitric oxide. In addition, a significant increase in the levels of tumor necrosis factor-alpha (TNF-α) and caspase-3 was detected in the two studied brain regions of rat model of SE. The activities of acetylcholinesterase (AchE) and Na+/K+-ATPase decreased significantly in the cortex and hippocampus of rat model of SE. Protection with Cur-NP prevented oxidative stress and improved the elevated level of caspase-3 in the hippocampus and cortex and the hippocampal TNF-α to nonsignificant changes. Although Cur-NP prevented the decrease in AchE activity in the two studied brain regions, it failed to return Na+/K+-ATPase activity to its normal value. Conclusions It is clear from the present findings that Cur-NP could prevent the oxidative stress and neuroinflammation and cell death that were induced during SE. This in turn may help in ameliorating the subsequent cascades of events that follow SE and its development into epileptogenesis.

scholarly journals Melatonin attenuates hypertension and oxidative stress in a rat model of L-NAME-induced gestational hypertension

2020 ◽  
Vol 25 (4) ◽  
pp. 295-301 ◽  
Author(s):  
Junfang Zuo ◽  
Ziyun Jiang
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Protein Content ◽  
Rat Model ◽  
Gestational Hypertension ◽  
Systemic Disease ◽  
Fetal Weight ◽  
Therapeutic Effects ◽  
Urine Protein ◽  
Plasma Antioxidant Capacity

Preeclampsia is a life-threatening multiorgan systemic disease with manifestations including gestational hypertension, oxidative stress, and vascular dysfunction. We aimed to evaluate the therapeutic effects of melatonin on an L-NAME (NLG-nitro-l-arginine methyl ester)-induced rat preeclampsia model. During gestation, L-NAME was added to drinking water at 50 mg/kg/day from gestation day (GD) 8. Rats received the combination of L-NAME with melatonin (10 mg/kg/day), or aspirin (1.5 mg/kg/day), and rats that received only L-NAME or no treatments were used as controls. Aspirin was mixed with rodent chow and melatonin was administered intraperitoneally. Blood pressure and urine protein content were monitored every 3 days. On GD19, blood samples were collected for biochemical analysis. Compared to untreated L-NAME rats, melatonin led to markedly lowered blood pressure and urine protein content, and recovery in the fetus alive ratio, fetal weight, and the fetal weight/placental weight ratio. Compared to untreated L-NAME rats, plasma antioxidant capacity and plasma malondialdehyde were increased and decreased by melatonin, respectively, in L-NAME rats. Melatonin treatment also reduced sFlt-1, increased PlGF, and decreased the sFlt-1/PlGF ratio. In the placenta, melatonin also reduced sFlt-1 levels and increased Nrf2, PlGF, and HO-1 levels. We have demonstrated in a rat model of preeclampsia that melatonin exerts significant protective effects through lowering blood pressure and reducing oxidative stress.

scholarly journals Placenta-Derived Mesenchymal Stem Cells Restore the Ovary Function in an Ovariectomized Rat Model via an Antioxidant Effect

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 591
Author(s):  
Jin Seok ◽  
Hyeri Park ◽  
Jong Ho Choi ◽  
Ja-Yun Lim ◽  
Kyung Gon Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Ovarian Function ◽  
Ovariectomized Rat ◽  
Therapeutic Effects ◽  
Ovary Function ◽  
Effect Of Pd ◽  
Antioxidant Markers

Oxidative stress is one of the major etiologies of ovarian dysfunction, including premature ovarian failure (POF). Previous reports have demonstrated the therapeutic effects of human placenta-derived mesenchymal stem cells (PD-MSCs) in an ovariectomized rat model (OVX). However, their therapeutic mechanism in oxidative stress has not been reported. Therefore, we investigated to profile the exosome of serum and demonstrate the therapeutic effect of PD-MSCs transplantation for the ovary function. We established an OVX model by ovariectomy and PD-MSCs transplantation was conducted by intravenous injection. Additionally, various factors in the exosome were profiled by LC-MS analysis. As a result, the transplanted PD-MSCs were engrafted into the ovary and the existence of antioxidant factors in the exosome. A decreased expression of oxidative stress markers and increased expression of antioxidant markers were shown in the transplantation (Tx) in comparison to the non-transplantation group (NTx) (* p < 0.05). The apoptosis factors were decreased, and ovary function was improved in Tx in comparison to NTx (* p < 0.05). These results suggest that transplanted PD-MSCs restore the ovarian function in an OVX model via upregulated antioxidant factors. These findings offer new insights for further understanding of stem cell therapy for reproductive systems.

Sign in / Sign up

Export Citation Format

Share Document