scholarly journals Carvedilol Exerts Neuroprotective Effect on Rat Model of Diabetic Neuropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Rania M. Magadmi ◽  
Mujahid A. Alsulaimani ◽  
Aziza R. Al-Rafiah ◽  
Muhammad Saeed Ahmad ◽  
Ahmed Esmat

Diabetic neuropathy (DN) commonly occurs in diabetics, affecting approximately 50% of both type 1 and 2 diabetic patients. It is a leading cause of non-traumatic amputations. Oxidative stress could play a key role in the pathophysiology of DN. This study aimed to investigate the potential neuroprotective effect of carvedilol on STZ-induced DN in rats. Thirty male Sprague Dawley rats (weighing 200–250 g) were randomly divided into five groups (six/group), where group 1 (negative control) received only the vehicle (0.5% of carboxymethyl cellulose orally 1 ml/kg). DN was induced by a single injection of remaining rats with streptozotocin (STZ; 50 mg/kg, i.p.). After diabetes induction, group 2 served as the diabetic untreated animals; while groups 3 and 4 were treated with carvedilol (1 and 10 mg/kg/d, orally, respectively). Group 5 received a-lipoic acid as a reference neuroprotective (100 mg/kg/d, orally). All treatments were continued for 45 days after diabetes induction, followed by behavioural tests. After sacrificing the animals, dorsal root ganglia, and sciatic nerves were collected for histopathological examination and biochemical assessments. Briefly, STZ administration caused cold allodynia, induced oxidative stress, and increased nerve growth factor (NGF) concentration. Nevertheless, carvedilol improved the behavioural tests, ameliorated the oxidative imbalance as manifested by reducing malondialdehyde, restoring glutathione content, and superoxide dismutase activity. Carvedilol also decreased NGF concentration in DRG homogenate. In conclusion, this study demonstrates the neuroprotective effect of carvedilol in an experimentally induced DN rat model through–at least partly–its antioxidant effect and reduced NGF concentration in DRG.

2019 ◽  
Vol 9 (5) ◽  
pp. 108 ◽  
Author(s):  
Abdelaziz M. Hussein ◽  
Mohamed Eldosoky ◽  
Mohamed El-Shafey ◽  
Mohamed El-Mesery ◽  
Khaled M. Abbas ◽  
...  

Objectives: To study the possible anti-seizure and neuroprotective effect of glucagon like peptide 1 (GLP1) analogue (liraglutide) in a pentylenetetrazole (PTZ) induced kindled rat model and its underlying mechanisms. Methods: Thirty Sprague Dawley rats were allocated into 3 equal groups; i) Normal group: normal rats received normal saline, ii) PTZ (kindling) group: received PTZ (50 mg/Kg intraperitoneally (i.p.)) every other day for 2 weeks and iii) PTZ + GLP1 group: same as the PTZ group but rats received liraglutide (75 µg/kg i.p. daily) for 2 weeks before PTZ injection. Seizure severity score, seizure latency and duration were assessed. Also, the expression of caspase-3 (apoptotic marker) and β-catenin (Wnt pathway) by western blotting, markers of oxidative stress (GSH, CAT and MDA) by biochemical assay and the expression of LC3 (marker of autophagy) and heat shock protein 70 (Hsp70) by immunostaining were assessed in hippocampal regions of brain tissues. Results: PTZ caused a significant increase in Racine score and seizure duration with a significant decrease in seizure latency. These effects were associated with a significant increase in MDA, β-catenin, caspase-3, Hsp70 and LC3 in brain tissues (p < 0.05). Meanwhile, liraglutide treatment caused significant attenuation in PTZ-induced seizures, which were associated with significant improvement in markers of oxidative stress, reduction in LC3, caspase-3 and β-catenin and marked increase in Hsp70 in hippocampal regions (p < 0.05). Conclusion: Activation of GLP1R might have anticonvulsant and neuroprotective effects against PTZ-induced epilepsy. These effects could be due to suppression of oxidative stress, apoptosis and autophagy and upregulation of Hsp70.


2017 ◽  
Vol 9 (2) ◽  
pp. 196 ◽  
Author(s):  
Hamed R. Takruri ◽  
Maha S. Shomaf ◽  
Saida F. Shnaigat

This research was conducted to study the protective effect of bee honey on the 7,12-dimethylbenz(a)anthracene (DMBA)- induced breast cancer in rat model. The study consisted of three groups: honey group, positive control group (PC), and negative control group (NC) to which the carcinogen was not administered. All rats were fed the diet recommended by the American Institute of Nutrition for growing rats (AIN-93G), with addition of honey (50 g/kg diet) to the honey group. All Rats were fed their diets ad libitum on 12 hours dark/light cycle. At the age of 50 days all rats in the honey and PC groups were gavaged once by the carcinogen DMBA with a dose of 80 mg/kg body Wt. After three weeks of carcinogen administration, rats were palpated weekly to detect any tumor growth. After 18 weeks, all rats were sacrificed. The palpable structures and the mammary glands along with associated lymph nodes were removed and fixed in saline formalin and prepared for histopathological examination. The results revealed that the honey group diet significantly (p < 0.05) reduced the incidence rate of mammary cancer, palpable tumor multiplicity, tumor size and weight compared to the PC group. In conclusion, multi floral honey has a protective effect against DMBA- induced mammary cancer in the initiation, promotion, and progression stages of DMBA-induced mammary carcinogenesis. However, further research is needed to reveal the mechanisms that might have contributed to the preventive effect of honey against mammary cancer.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Zhixing Jin ◽  
Li Wang ◽  
Zhiling Zhu

Objective. To evaluate the effect of GuiXiong Xiaoyi Wan (GXXYW) on the development of endometriosis in a rat model.Methods. Sprague-Dawley rats with surgically induced endometriosis were randomly treated with low-dose GXXYW, high-dose GXXYW, or vehicle (negative control) for 28 days. Immunohistochemistry was used to assess cell proliferation in the lesions. The terminal deoxynucleotidyl transferase- (TdT-) mediated dUTP biotin nick end labelling (TUNEL) method was performed to analyse the apoptosis induced by GuiXiong Xiaoyi Wan. The percentages of CD3+ lymphocytes, CD4+ lymphocytes, and CD8+ lymphocytes in the spleens of the rats were evaluated using flow cytometric analysis.Results. Treatment with GXXYW significantly decreased the lesion size, inhibited cell proliferation, and induced apoptosis in endometriotic tissue. The spleens of GXXYW-treated rats also demonstrated a significant increase in the percentage of CD4+ lymphocytes and a significant decrease in the percentage of CD8+ lymphocytes.Conclusions. These results suggest that, in a rat model, GXXYW may be effective in the suppression of the growth of endometriosis, possibly through the inhibition of cell proliferation, the induction of apoptosis of endometriotic cells, and the regulation of the immune system.


Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 685-686
Author(s):  
Anca D Dobrian ◽  
Michael J Davies ◽  
Suzanne D Schriver ◽  
Thomas J Lauterio ◽  
Russell L Prewitt

45 The mechanisms underlying the development of hypertension in obesity are not yet fully understood. We recently reported the development of hypertension in a rat model of diet-induced obesity (Dobrian AD et al Hypertension 2000;35: in press). When Sprague-Dawley rats (n=60) are fed a moderately high fat diet(32kcal% fat) for 10-16 weeks, about half of them develop obesity (obesity-prone (OP) and mild hypertension (153±3.4 mmHg systolic pressure), whereas the other half (obesity-resistant, OR) maintains body weight equivalent to low fat control (C) and are normotensive. We examined the potential role of oxidative stress in the development of hypertension in this model. Lipid peroxides measured as thiobarbituric acid reactive substances (TBARS) are showing a significant increase in the LDL fraction of OP rats (2.8±0.32 nmol MDA/mg protein) compared to OR and C (0.9±0.3 nmol MDA/mg protein). Also, aortic and kidney TBARS showed a significant 3- and 5- fold increase in OP rats after 16 weeks of diet (3.3±0.44 aorta and 6.7±0.52 nmol MDA/mg protein kidney) vs OR. In addition, superoxide generation by aortic rings, measured by lucigenin (25μM) luminescence showed a 2-fold increase in the OP group (4325.6±174 RLU/15 min/mg DNA X10 5 ) compared to both OR and C. Plasma renin activity was 2-fold increased in OP vs both OR and control groups.The urine nitrate/nitrite measured by LDH colorimetric method showed a 1.8-fold decrease in OP rats (2.4±0.17 μmoles) compared to OR. A similar 1.6-fold decrease was found for plasma nitrate/nitrite in OP rats vs OR and C. However, eNOS expression assessed by semiquantitative RT-PCR showed a strong increase in the OP rats vs OR and controls in both kidney cortex(eNOS/β-actin ratio of 0.78±0.21 in OP vs 0.32±0.16 in OR)and medulla(0.86±0.18 in OP vs 0.36±0.14 in OR), suggesting a possible shift toward superoxide vs NO production by the eNOS enzyme.Also, eNOS expression was increased ∼4.8-fold in the thoracic aorta of OP compared to OR rats. Collectively, data show a decreased NO production in OP animals, due in part to the increased oxidative stress, possibly generated by the activation of renin-angiotensin system and increased eNOS expression.


Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Jing Xu ◽  
Guanghui Zheng ◽  
Juntao Hu ◽  
Weiwei Ge ◽  
Jennifer Bradley ◽  
...  

Introduction: JZL184 is a synthetic monoacylglycerol lipase inhibitor that reduces brain edema, infarct size and alleviates inflammation following cerebral ischemia in experimental studies. In this study, we compared its cerebral protective effects with therapeutic hypothermia following cardiopulmonary resuscitation (CPR) in a rat model. Hypothesis: JZL184 will have similar neuroprotective effects to therapeutic hypothermia after cardiac arrest (CA) by reducing brain and blood brain barrier (BBB) injury and preserving cerebral microcirculation following CPR. Methods: Thirty six male Sprague-Dawley rats weighing between 450-550 g were randomized: 1) control 2) hypothermia 3) JZL184. Ventricular fibrillation was induced and untreated for 6 min for all rats. Resuscitation was attempted with a 4 Joule defibrillation after 8 min of CPR. Immediately following resuscitation, either hypothermia (33+0.5 o C) or JZL184 (16 mg/k, IP) was administered. Cerebral microcirculation, S-100β, NSE and Evan’s Blue (EB) concentrations were analyzed at 6hrs after resuscitation. Results: NSE and S-100β levels were higher in control compared to hypothermia and JZL18 at 6hr post ROSC (p < 0.001) (Fig. 1). Compared with control, there was a significant decrease in brain permeability to EB in Hypothermia and JZL184 after 6hr post ROSC (p<0.001) (Fig. 2). Microvascular flow index (MFI) was reduced in control compared with hypothermia and JZL184 6hr post ROSC (p <0.01). Conclusions: JZL184 administered following resuscitation reduced brain and BBB injury and preserved cerebral microcirculation at 6 hr post arrest to the same extent as hypothermia in a rat model of cardiac arrest.


2017 ◽  
Vol 16 (1) ◽  
pp. 167-167
Author(s):  
M.S. Berke ◽  
Klas S.P. Abelson

Abstract Aims This study investigated the effects of buprenorphine treatment on pain and welfare parameters and model specific parameters in a rat model of monoarthritis to eliminate unnecessary pain from this model. Methods 32 male Sprague Dawley rats were divided into four groups: (1) A negative control without arthritis receiving no analgesia. (2) A positive monoarthritic control group receiving no analgesia, but subcutaneous saline injections twice a day. (3) A positive control with monoarthritis receiving subcutaneous carprofen once a day and saline once a day. (4) A group with monoarthritis receiving subcutaneous buprenorphine twice a day. Monoarthritis was induced with an injection of 0.02 ml Complete Freund’s Adjuvant intra-articularly in the left tibiotarsal joint. Treatment with analgesia was initiated at day 15 and the rats were euthanized at day 23. Results The induced monoarthritis elicited a pronounced acute inflammation. Several parameters such as bodyweight, mobility, stance, joint-stiffness and lameness scores were affected. A marked mechanical hyperalgesia in the tarsal area was observed by Electronic Von Frey testing, but no severe compromise of the animal welfare was seen at any time. Signs of chronic development began to appear from day 10 after the monoarthritic induction. No significant change in serum cytokines and faecal corticosterone measurements was found after administration of buprenorphine. A minor decrease in body weight was seen, and a higher pain tolerance to mechanical stimuli was observed, indicating pain alleviation. The histological examination confirmed monoarthritic development in all monoarthritic rats and revealed periarticular lesions suggesting diffusion of adjuvant from intra-articular injection site to the periphery. Conclusions The study demonstrated that buprenorphine has an analgesic effect in the adjuvant induced monoarthritic rat model, without obvious interference with the development of arthritis.


2019 ◽  
Vol 172 (1) ◽  
pp. 132-145 ◽  
Author(s):  
Silvia Cirillo ◽  
Fabio Vivarelli ◽  
Eleonora Turrini ◽  
Carmela Fimognari ◽  
Sabrina Burattini ◽  
...  

Abstract Despite the knowledge gap regarding the risk-benefit ratio of the electronic cigarette (e-cig), its use has grown exponentially, even in teenagers. E-cig vapor contains carcinogenic compounds (eg, formaldehyde, acetaldehyde, and acrolein) and free radicals, especially reactive oxygen species (ROS) that cause toxicological effects, including DNA damage. The role of e-cig voltage customization on molecule generation has been reported, but the effects of the resistance on e-cig emissions and toxicity are unknown. Here, we show that the manipulation of e-cig resistance influences the carbonyls production from nonnicotine vapor and the oxidative and inflammatory status in a rat model. Fixing the voltage at the conventional 3.5 V, we observed that the amount of the selected aldehydes increased as the resistance decreased from 1.5 to 0.25 Ω. Under these conditions, we exposed Sprague Dawley rats to e-cig aerosol for 28 days, and we studied the pulmonary inflammation, oxidative stress, tissue damage, and blood homeostasis. We found a perturbation of the antioxidant and phase II enzymes, probably related to the increased ROS levels due to the enhanced xanthine oxidase and P450-linked monooxygenases. Furthermore, frames from scanning electron microscope showed a disorganization of alveolar and bronchial epithelium in 0.25 Ω group. Overall, various toxicological outcomes, widely recognized as smoke-related injuries, can potentially occur in e-cig consumers who use low-voltage and resistance device. Our study suggests that certain “tips for vaping safety” cannot be established, and encourages further independent investigations to help public health agencies in regulating the e-cig use.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hoon Jang ◽  
Woong-Jin Bae ◽  
Seung-Mo Yuk ◽  
Dong-Seok Han ◽  
U-Syn Ha ◽  
...  

Seoritae is a type of black soybean that is known to have health-promoting effects due to its high isoflavone and anthocyanin contents. We evaluated whether Seoritae extract (SE) had beneficial effects on the reduction of prostate weight in a rat model of benign prostatic hyperplasia (BPH). BPH was induced by intramuscular injections of testosterone enanthate once a week for 5 weeks in Sprague-Dawley rats, and rats were treated with or without daily oral doses of SE during BPH induction. After 5 weeks, the oxidative stress (superoxide dismutase and 8-hydroxy-2-deoxyguanosine), apoptosis (caspase-3), and activity of 5-alpha reductase were evaluated in the serum and prostate. The SE treatment group showed a significant decrease in prostate weight, oxidative stress, apoptosis, and 5-alpha reductase activity compared to the nontreated BPH group. These results show that SE is effective in decreasing the weight and proliferation of the prostate, and suggest that SE may be an effective treatment for BPH.


2021 ◽  
Vol 26 (2) ◽  
pp. 56-63
Author(s):  
Iman R. S. Al-Qalhati ◽  
Mostafa Ibrahim Waly ◽  
Lyutha Al-Subhi ◽  
Zahir Al-Attabi

Background:The use of plant for medicinal purposes has a long history worldwide.  There is a lack of research that identifies the antidiabetic effect of edible Omani wild plants. Oxidative stress mediates the pathogenesis of diabetes and it has been suggested that natural antioxidants might be considered as an effective intervention for combating diabetes. Objective: This study aimed to assess the anti-diabetic and antioxidant potential properties of two edible Omani wild plants (Pteropyrum scoparium and Oxalis corniculata) or their mixture in streptozotocin (STZ)-induced diabetic rats. Methods: Thirty-seven male Sprague Dawley rats, weighting 250–300 grams, were allocated into 5 groups: non-diabetic (9 rats/group), diabetic group (7 rats/group), and three diabetic groups that received oral feeding of either Pteropyrum scoparium, Oxalis corniculata, or their mixture (7 rats/group). Diabetes was induced by a single intraperitoneal injection dose of STZ drug, 50 mg/kg body weight. At the end of the experimental trial, after 8 weeks, all rats were fasted overnight and sacrificed; blood glucose was measured, meanwhile pancreatic tissues were dissected and homogenized for the biochemical assessment of oxidative stress markers (glutathione, GSH, and total antioxidant capacity, TAC). Results: STZ resulted in hyperglycemia and oxidative stress (GSH depletion and TAC impairment) in diabetic group as compared to non-diabetic group. Meanwhile the concomitant treatment of diabetic groups with the two wild the edible Omani plants or their mixture have shown a protective effect against the STZ-induced hyperglycemia, but with no effect on oxidative stress. It was noted that for the final boy weight, the improvement was not significant as well. Histopathological examination of the pancreatic tissues showed that the STZ injection lead to pathological changes associated with diabetes in the pancreatic tissues of all diabetic groups. Conclusion:  Pteropyrum scoparium and Oxalis corniculata combated the STZ-induced hyperglycemia with no effect on oxidative stress. Also, there was no synergistic effect of Pteropyrum scoparium and Oxalis corniculata on hyperglycemia or oxidative stress.


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