Electroacupuncture Relieves Labour Pain and Influences the Spinal Dynorphin/κ-Opioid Receptor System in Rats

2016 ◽  
Vol 34 (3) ◽  
pp. 223-228 ◽  
Author(s):  
Qiu-Yan Jiang ◽  
Meng-Ying Wang ◽  
Li Li ◽  
Hai-Xia Mo ◽  
Jin-Ling Song ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Opioid Receptor ◽  
Rat Model ◽  
Acupuncture Point ◽  
Labour Pain ◽  
Mechanisms Of Action ◽  
Lumbar Spinal Cord ◽  
Control Group ◽  
Tail Flick ◽  
Underlying Mechanisms

Background The dynorphin (DYN)/κ-opioid receptor (KOR) system plays a key role in the control of labour pain. Our previous clinical study reported that electroacupuncture (EA) provided intrapartum analgesia, but the underlying mechanisms of action have not been fully elucidated. Aims To observe the effect of EA on labour pain and to explore the underlying mechanisms of action in a rat model. Methods Copulation-confirmed pregnant rats (n=120) were given castor oil to induce labour. Rats remained untreated (control group, n=20) or received either meperidine (an opioid that is commonly used to treat labour pain, n=20) or EA at SP6, LI4, SP6+LI4 or SP10 (four groups, n=20 each). Labour pain was evaluated by the warm water tail-flick test. Serum DYN values were measured by ELISA. Protein and mRNA expression of prodynorphin (PDYN, the precursor protein of DYN) and KOR were analysed by Western blotting and real-time PCR, respectively. Results EA treatment at all acupuncture point combinations studied significantly relieved labour pain and increased serum DYN concentrations, to a degree similar to that achieved with meperidine. EA notably enhanced protein expression of KOR and PDYN and mRNA expression in the lumbar spinal cord but not in the cerebral cortex. The size of effect varied by EA group in the order: SP6>LI4>SP6+LI4>SP10 for all parameters measured, indicating differential effects relating to acupuncture point selection/combination. Conclusions The present study indicates that EA relieves labour pain, at least in part, by regulation of the spinal DYN/KOR system in a rat model.

scholarly journals A Subpressor Dose of Angiotensin II Elevates Blood Pressure in a Normotensive Rat Model by Oxidative Stress

2015 ◽  
pp. 153-159 ◽  
Author(s):  
M. M. GOVENDER ◽  
A. NADAR
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Mrna Expression ◽  
Rat Model ◽  
Wistar Rat ◽  
Control Group ◽  
Sod Activity ◽  
Male Wistar Rats ◽  
Experimental Group

Oxidative stress is an imbalance between free radicals and antioxidants, and is an important etiological factor in the development of hypertension. Recent experimental evidence suggests that subpressor doses of angiotensin II elevate oxidative stress and blood pressure. We aimed to investigate the oxidative stress related mechanism by which a subpressor dose of angiotensin II induces hypertension in a normotensive rat model. Normotensive male Wistar rats were infused with a subpressor dose of angiotensin II for 28 days. The control group was sham operated and infused with saline only. Plasma angiotensin II and H2O2 levels, whole-blood glutathione peroxidase, and AT-1a, Cu/Zn SOD, and p22phox mRNA expression in the aorta was assessed. Systolic and diastolic blood pressures were elevated in the experimental group. There was no change in angiotensin II levels, but a significant increase in AT-1a mRNA expression was found in the experimental group. mRNA expression of p22phox was increased significantly and Cu/Zn SOD decreased significantly in the experimental group. There was no significant change to the H2O2 and GPx levels. Angiotensin II manipulates the free radical-antioxidant balance in the vasculature by selectively increasing O2− production and decreasing SOD activity and causes an oxidative stress induced elevation in blood pressure in the Wistar rat.

P3486Experimental model for heart failure in rats: apelin-13/apj and bnp-45 gene expression analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H R Helmi ◽  
A P Sunjaya ◽  
D Limanan ◽  
A R Prijanti ◽  
S W A Jusman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Mrna Expression ◽  
Rat Model ◽  
Control Group ◽  
P Value ◽  
Sprague Dawley ◽  
Hypoxia Exposure ◽  
Systemic Hypoxia

Abstract Background Apelin, an adipokine peptide and its receptor has recently emerged as a key signaling pathway in maintaining cardiac performance at chronic pressure loads. Apelin has been linked to ventricular dysfunction and therefore maybe of pathophysiologic relevance as a candidate biomarker in HF patients. Purpose This study aims to investigate Apelin-13 gene expression and level, and Apelin receptor (APJ) level in a rat model of heart failure induced by chronic systemic hypoxia and their correlation to BNP-45 gene expression and level, the current gold standard biomarker for heart failure, and to cardiac histopathologic changes. The effect of chronic systemic hypoxia on cardiac hypertrophy, remodeling and heart failure parameters is also of interest. Methods Twenty-eight male Sprague-Dawley rats (8–12 weeks of age) were placed in special hypoxic chambers divided into 7 groups – a control group provided with normoxia (atmospheric O2 levels) and 6 exposure groups exposed to hypoxia (8% O2) for 6 hours, 1, 3, 5, 7 and 14 days respectively prior to measurement. Changes in the expression of Apelin and BNP-45 were measured using quantitative real-time PCR, whereas changes in Apelin-13, APJ and BNP-45 levels were measured using ELISA. Histopathology staining using Hematoxylin and Eosin was performed on cardiac tissues post-termination. Results Compared to control, BNP-45 mRNA expression in the hypoxic heart was only significantly different in day 14, whereas, Apelin mRNA expression had showed significantly higher values starting from day 7 onward. This is in line with the evidence of cardiac hypertrophy based on histopathologic examination present from day 7 onwards. BNP-45 and Apelin-13 levels were significantly higher compared to control from day 5 onwards with a peak on day 7. Although significantly higher than control, Apelin-13 and BNP-45 level decreases in day 14 as compared to day 7. Mean APJ levels showed a similar profile with Apelin-13 and BNP-45 levels with a peak in day 7 (4.619 ng/mL). The cardiac Apelin-13 level shows strong significant correlation with BNP-45 levels (r 0.823, p-value 0.0001). There was also a strong significant correlation between APJ receptor levels with Apelin-13 (r 0.9029, p-value 0.001) and BNP-45 (r 0.9062, p-value 0.0009) levels. Apelin-13, APJ and BNP-45 levels also showed strong significant positive correlation to the duration of hypoxia exposure. Conclusion Chronic (≥5 days) and not acute systemic hypoxia in an experimental rat model leads to increase in Apelin-13, APJ and BNP-45 levels. Apelin-13 and BNP-45 were found to significantly increase from 5 days onwards. Apelin mRNA expression was found to show significant increase earlier compared to BNP-45 mRNA expression. Hence, Apelin may serve as a new candidate biomarker for detection of HF due to oxidative stress compared to BNP-45. Exposure to chronic systemic hypoxia can serve as an easily replicable rat model for heart failure. Acknowledgement/Funding Department of Biochemistry and Molecular Biology, Faculty of Medicine, Tarumanagara University, Jakarta, Indonesia

scholarly journals Electroacupuncture Alleviates Pain Responses and Inflammation in a Rat Model of Acute Gout Arthritis

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Wenxin Chai ◽  
Yan Tai ◽  
Xiaomei Shao ◽  
Yi Liang ◽  
Guo-qing Zheng ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Rat Model ◽  
Analgesic Effect ◽  
Thermal Hyperalgesia ◽  
Acute Gout ◽  
Inflammatory Conditions ◽  
Opioid Receptor Antagonists ◽  
Underlying Mechanisms ◽  
The One ◽  
Opioid Receptor Agonists

Acute gout arthritis is one of the most painful inflammatory conditions. Treatments for gout pain are limited to colchicine, nonsteroidal anti-inflammatory drugs, and corticosteroids, which oftentimes result in severe adverse effects. Electroacupuncture (EA) has been proved to be effective in relieving many inflammatory pain conditions with few side effects. Here, we aim to investigate the therapeutic potentials of EA on pain and inflammation of a rat model of acute gout arthritis and underlying mechanisms. We found that 2/100 Hz EA produced the most robust analgesic effect on mechanical hyperalgesia of acute gout arthritis rat model compared with 2 and 100 Hz. EA produced similar analgesic effect compared with indomethacin. 2/100 Hz EA also significantly alleviates the ongoing pain behavior, thermal hyperalgesia, and ankle edema. Locally applied μ and κ-opioid receptor antagonists but not adenosine A1 receptor antagonist significantly abolished the analgesic effect of EA. Locally applied μ and κ-opioid receptor agonists produced significant antiallodynia on acute gout arthritis rats, mimicking EA. Furthermore, 2/100 Hz EA upregulated β-endorphin expression in inflamed ankle skin tissue. Our results demonstrated, for the first time, that EA can be used for relieving acute gout arthritis with effect dependent on peripheral opioid system and comparable with the one obtained with indomethacin.

scholarly journals Effect of Electroacupuncture Pretreatment at Gb20 on Behaviour and the Descending Pain Modulatory System in a Rat Model of Migraine

2016 ◽  
Vol 34 (2) ◽  
pp. 127-135 ◽  
Author(s):  
Pei Pei ◽  
Lu Liu ◽  
Luopeng Zhao ◽  
Yingxue Cui ◽  
Zhengyang Qu ◽  
...  
Keyword(s):  
Rat Model ◽  
Acupuncture Point ◽  
Sham Acupuncture ◽  
Control Group ◽  
Drinking Behaviour ◽  
Neural Activation ◽  
Model Group ◽  
Sprague Dawley ◽  
Descending Pathways ◽  
Conscious Rat

Background While electroacupuncture (EA) pretreatment has been found to ameliorate migraine-like symptoms, the underlying mechanisms remain poorly understood. Emerging evidence suggests that the brainstem descending pain modulatory system, comprising the periaqueductal grey (PAG), raphe magnus nucleus (RMg), and trigeminal nucleus caudalis (TNC), may be involved in migraine pathophysiology. We hypothesised that EA would ameliorate migraine-like symptoms via modulation of this descending system. Methods We used a conscious rat model of migraine induced by repeated electrical stimulation of the dura. Forty male Sprague-Dawley rats were randomly assigned to one of four groups: an EA group, which received EA at GB20 following dural stimulation; a sham acupuncture (SA) group, which received manual acupuncture at a non-acupuncture point following dural stimulation; a Model group, which received dural stimulation but no acupuncture; and a Control group, which received neither dural stimulation nor acupuncture (electrode implantation only). HomeCageScan was used to measure effects on behaviour, and immunofluorescence staining was used to examine neural activation (c-Fos immunoreactivity) in the PAG, RMg, and TNC. Results Compared to the Model group, rats in the EA group showed a significant increase in exploratory, locomotor and eating/drinking behaviour (p<0.01) and a significant decrease in freezing-like resting and grooming behaviour (p<0.05). There was a significant increase in the mean number of c-Fos neurons in the PAG, RMg, and TNC in Model versus Control groups (p<0.001); however, this was significantly attenuated by EA treatment (p<0.001). There were no significant differences between the SA and Model groups in behaviour or c-Fos immunoreactivity. Conclusions EA pretreatment ameliorates behavioural changes in a rat model of recurrent migraine, possibly via modulation of the brainstem descending pathways.

scholarly journals Electroacupuncture Regulates Disorders of Gut-Brain Interaction by Decreasing Corticotropin-Releasing Factor in a Rat Model of IBS

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Ying Chen ◽  
Yan Zhao ◽  
Dan-ni Luo ◽  
Hui Zheng ◽  
Ying Li ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Rat Model ◽  
Pain Threshold ◽  
Visceral Pain ◽  
Sucrose Preference ◽  
Control Group ◽  
Mild Stress ◽  
Double Staining ◽  
Blank Control Group ◽  
Treatment Groups

Objective. Acupuncture is effective for irritable bowel syndrome (IBS); however, the mechanisms of action are not fully understood. We aim to explore the mechanism of electroacupuncture (EA) in the dual regulation of disorders of gut-brain interaction. Methods. A rat model of IBS was generated by chronic unpredictable mild stress (CUMS). Eight of 32 rats were assigned to the blank control group. The remaining 24 rats received CUMS for 14 days. Then, the rats surviving and successfully modelled were randomly divided into the CUMS group, the CUMS+EA group, and the CUMS+PB (pinaverium bromide) group. In the next 14 days of treatment, rats in the CUMS+EA group were acupunctured at ST25 (Tianshu), ST36 (Zusanli), SP6 (Sanyinjiao), and LR3 (Taichong) for 15 min every day. Rats in the CUMS+PB group were treated by the administration of gavage with 2.7 mg/mL pinaverium every day. Visceral pain threshold, the percentage of time spent in open arms (OT%) in the elevated plus maze test (EPMT), and the sucrose preference (SP%) in the sucrose preference test (SPT) were measured at baseline, day 15, and day 30. The expression of zonula occludens-1 (ZO-1), the morphology of the connective structure of intestinal epithelium, the CRF and CRF-R1 mRNA expression in the hypothalamus, and the double staining of intestinal mucosal mast cells (IMMC) and CRF-R1 were measured at the end of the experiment. Results. Compared with the blank control group, visceral pain threshold pressure, the expression of ZO-1, OT%, SP%, CRF, and CRF-R1 mRNA expression in the hypothalamus, and double staining of IMMC and CRF-R1 were decreased significantly in the CUMS group. Meanwhile, the morphology of the connective structure in the CUMS group was indistinct. Compared with the CUMS group, SP% was significantly increased in the CUMS+EA group, but there was no significant difference for it in the CUMS+PB group. The morphology of the connective structure in the two treatment groups was clear and seeable. And the expression of other parameters mentioned above was apparently increased in the two treatment groups. Compared with the CUMS+PB group, the expression of ZO-1 in the CUMS+EA group was significantly enhanced. And no obvious difference for other parameters was found between the two treatment groups. Conclusions. EA treatment can decrease the expression of hypothalamic CRF and CRF-R1, relieve anxiety and depression, meanwhile reduce the expression of CRF-R1 in the gastrointestinal mucosa, increase ZO-1 expression, and adjust tight junctions (TJs) to repair the intestinal mucosal barrier. The above roles suggest that EA may play a dual role in alleviating the gastrointestinal and psychological symptoms of IBS, suggesting a potentially dual therapeutic role for EA in regulating disorders of gut-brain interaction in IBS rats.

scholarly journals Effect of Electroacupuncture on Hyperalgesia and Vasoactive Neurotransmitters in a Rat Model of Conscious Recurrent Migraine

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Xiaobai Xu ◽  
Lu Liu ◽  
Luopeng Zhao ◽  
Bin Li ◽  
Xianghong Jing ◽  
...  
Keyword(s):  
Rat Model ◽  
Single Point ◽  
Plasma Concentrations ◽  
Thermal Hyperalgesia ◽  
Acupuncture Point ◽  
Acupuncture Points ◽  
Tail Flick ◽  
Calcitonin Gene ◽  
Pituitary Adenylate Cyclase ◽  
Perivascular Nerves

Migraine onset is associated with the abnormal release of vasoactive neurotransmitters from perivascular nerves, and these neurotransmitters are involved in the pathophysiology of migraine. Hyperalgesia is a key feature of migraine, and accumulating evidence indicates that electroacupuncture (EA) at the single acupuncture point (Fengchi [GB20]) is effective in ameliorating hyperalgesia. In clinical practice, multiple acupuncture points are widely used, especially GB20 and Yanglingquan (GB34). However, the role played by vasoactive neurotransmitters in acupuncture antihyperalgesic effect at the single or multiple acupuncture points remains unknown. We aimed to determine whether EA would exert its antihyperalgesic effects by modulating vasoactive neurotransmitter release from the perivascular nerves. Furthermore, we examined whether targeting multiple acupuncture points would be more effective than targeting a single point in reducing hyperalgesia. The mechanical and thermal hyperalgesia were evaluated by measuring the facial and hind-paw mechanical withdrawal thresholds, tail-flick and hot-plate latencies. Plasma concentrations of vasoactive neurotransmitters were determined using rat-specific ELISA kits from jugular vein, including calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), pituitary adenylate cyclase-activating polypeptide (PACAP), nitric oxide (NO), and endothelin-1 (ET-1). The result suggested that EA significantly ameliorated the mechanical and thermal hyperalgesia, reduced c-Fos levels in the trigeminal ganglion, and attenuated plasma and dural levels of vasoactive neurotransmitters, especially in the multiple acupuncture points group (GB20+GB34). In conclusion, EA exerts antihyperalgesic effect in a rat model of conscious recurrent migraine, possibly via modulation of the vasoactive neurotransmitters. Furthermore, targeting multiple acupuncture points is more effective than targeting a single point in reducing hyperalgesia.

scholarly journals Dietary Beta-Hydroxy Beta-Methyl Butyrate Supplementation Alleviates Liver Injury in Lipopolysaccharide-Challenged Piglets

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yehui Duan ◽  
Bo Song ◽  
Changbing Zheng ◽  
Yinzhao Zhong ◽  
Qiuping Guo ◽  
...  
Keyword(s):  
Liver Injury ◽  
Mrna Expression ◽  
Basal Diet ◽  
Control Group ◽  
Protective Effects ◽  
Ampk Signaling ◽  
Lps Challenge ◽  
Hepatic Energy Metabolism ◽  
Serum Aspartate Aminotransferase ◽  
Underlying Mechanisms

The current study was performed to investigate whether dietary β-hydroxy-β-methylbutyrate (HMB) could regulate liver injury in a lipopolysaccharide- (LPS-) challenged piglet model and to determine the mechanisms involved. Thirty piglets ( 21 ± 2   days   old , 5.86 ± 0.18   kg body weight) were randomly divided into the control (a basal diet, saline injection), LPS (a basal diet), or LPS+HMB (a basal diet + 0.60% HMB-Ca) group. After 15 d of treatment with LPS and/or HMB, blood and liver samples were obtained. The results showed that in LPS-injected piglets, HMB supplementation ameliorated liver histomorphological abnormalities induced by LPS challenge. Compared to the control group, the activities of serum aspartate aminotransferase and alkaline phosphatase were increased in the LPS-injected piglets ( P < 0.05 ). The LPS challenge also downregulated the mRNA expression of L-PFK, ACO, L-CPT-1, ICDH β, and AMPKα1/2 and upregulated the mRNA expression of PCNA, caspase 3, TNF-α, TLR4, MyD88, NOD1, and NF-κB p65 ( P < 0.05 ). However, these adverse effects of the LPS challenge were reversed by HMB supplementation ( P < 0.05 ). These results indicate that HMB may exert protective effects against LPS-induced liver injury, and the underlying mechanisms might involve the improvement of hepatic energy metabolism via regulating AMPK signaling pathway and the reduction of liver inflammation via modulating TLR4 and NOD signaling pathways.

Effect of Transcutaneous Electrical Acupuncture Point Stimulation at Different Frequencies in a Rat Model of Neuropathic Pain

2017 ◽  
Vol 35 (2) ◽  
pp. 142-147 ◽  
Author(s):  
Xiangdi Yu ◽  
Fangxiang Zhang ◽  
Bingning Chen
Keyword(s):  
Neuropathic Pain ◽  
Rat Model ◽  
High Frequency ◽  
Low Frequency ◽  
Acupuncture Point ◽  
Control Group ◽  
High Frequency Stimulation ◽  
Sprague Dawley ◽  
Electrical Acupuncture ◽  
Frequency Stimulation

Background Acupuncture and related techniques are used worldwide to alleviate pain; however, their mechanisms of action are still not fully understood. In the present study, we investigated the effect of transcutaneous electrical acupuncture point stimulation (TEAS) at different frequencies in a chronic constriction injury (CCI) model of neuropathic pain in rats. Methods CCI was induced by ligating the common sciatic nerve, which produced neuropathic pain. 18 male Sprague–Dawley rats with CCI were randomly divided into three groups (n=6 each) that remained untreated (CCI group) or received TEAS at high frequency (CCI+TEAS-H group) or TEAS at low frequency (CCI+TEAS-L group). Rats in the CCI+TEAS-H group received high frequency stimulation (6–9 mA, 100 Hz) at GB34/GV26/ST36; those in the CCI+TEAS-L group received low frequency stimulation (6–9 mA, 2 Hz) at the same points. Rats in the control group had the same electrodes applied but received no stimulation. All three groups were subjected to behavioural studies after treatment. Expression of μ opioid receptors (MORs) in the L3–L5 dorsal root ganglion (DRG) was determined by immunofluorescence staining and Western blotting after treatment. Results Compared with the untreated CCI group, both mechanical allodynia and thermal hypergesia were significantly attenuated, and MOR expression in the DRG was significantly increased by low frequency TEAS treatment at GB34/GV26/ST36 (p<0.05). In contrast, no significant differences were observed between the CCI and CCI+TEAS-H groups. Conclusions The use of low frequency TEAS significantly mitigated neuropathic pain in this rat model, and its analgesic effect is likely mediated by upregulation of MOR expression in the DRG.

Autophagy Modulators and Neuroinflammation

2020 ◽  
Vol 27 (6) ◽  
pp. 955-982 ◽  
Author(s):  
Kyoung Sang Cho ◽  
Jang Ho Lee ◽  
Jeiwon Cho ◽  
Guang-Ho Cha ◽  
Gyun Jee Song
Keyword(s):  
Neurodegenerative Disorders ◽  
Neurological Disorders ◽  
Mammalian Cells ◽  
Critical Role ◽  
Therapeutic Agents ◽  
Mechanisms Of Action ◽  
Scientific Interest ◽  
Therapeutic Tools ◽  
Underlying Mechanisms

Background: Neuroinflammation plays a critical role in the development and progression of various neurological disorders. Therefore, various studies have focused on the development of neuroinflammation inhibitors as potential therapeutic tools. Recently, the involvement of autophagy in the regulation of neuroinflammation has drawn substantial scientific interest, and a growing number of studies support the role of impaired autophagy in the pathogenesis of common neurodegenerative disorders. Objective: The purpose of this article is to review recent research on the role of autophagy in controlling neuroinflammation. We focus on studies employing both mammalian cells and animal models to evaluate the ability of different autophagic modulators to regulate neuroinflammation. Methods: We have mostly reviewed recent studies reporting anti-neuroinflammatory properties of autophagy. We also briefly discussed a few studies showing that autophagy modulators activate neuroinflammation in certain conditions. Results: Recent studies report neuroprotective as well as anti-neuroinflammatory effects of autophagic modulators. We discuss the possible underlying mechanisms of action of these drugs and their potential limitations as therapeutic agents against neurological disorders. Conclusion: Autophagy activators are promising compounds for the treatment of neurological disorders involving neuroinflammation.

Apoptotic Effects of Melittin on 4T1 Breast Cancer Cell Line is associated with Up Regulation of Mfn1 and Drp1 mRNA Expression

2020 ◽  
Vol 20 (7) ◽  
pp. 790-799 ◽  
Author(s):  
Farnaz D. Moghaddam ◽  
Pejman Mortazavi ◽  
Somayeh Hamedi ◽  
Mohammad Nabiuni ◽  
Nasim H. Roodbari
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Hemolytic Activity ◽  
Breast Cancer Cells ◽  
Flow Cytometric Analysis ◽  
Control Group ◽  
Flow Cytometric ◽  
4T1 Cells ◽  
4T1 Breast Cancer ◽  
Apoptotic Effects

Background and Purpose: Melittin, as the main ingredient of honeybee venom, that has shown anticancer properties. The present study aimed at investigating the cytotoxic impacts of melittin on 4T1 breast cancer cells. Methods: Hemolytic activity of different concentrations (0.125, 0.25, 0.5, 1, 2, 4, 8μg/ml) of melittin was assayed and then cytotoxicity of selected concentrations of melittin (2, 4, 8, 16, 32, and 64μg/ml), 2 and 4μg/ml of cisplatin and 0.513, 0.295 and 0.123μg/ml of doxorubicin was evaluated on 4T1 cells using MTT assay. We used Morphological evaluation and flow cytometric analysis was used. Real time PCR was also used to determine mRNA expression of Mfn1 and Drp1 genes. Results: All compounds showed anti-proliferative effects on the tumor cell line with different potencies. Melittin had higher cytotoxicity against 4T1 breast cancer cells (IC50= 32μg/ml-72h) and higher hemolytic activity (HD50= 1μg/ml), as compared to cisplatin and doxorubicin. Mellitin at 16 and 32μg/ml showed apoptotic effects on 4T1 cells according to the flow cytometric analysis. The Real time PCR analysis of Drp1 and Mfn1 expression in cells treated with 16μg/ml of melittin revealed an up-regulation in Drp1 and Mfn1 genes mRNA expression in comparison with control group. Treatment with 32μg/ml of melittin was also associated with a rise in mRNA expression of Drp1 and Mfn1 as compared to the control group. Conclusion: The results of this study showed that melittin has anticancer effects on 4T1 cell lines in a dose and time dependent manner and can be a good candidate for further research on breast cancer treatment.

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