scholarly journals Apigenin Attenuates Adriamycin-Induced Cardiomyocyte Apoptosis via the PI3K/AKT/mTOR Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Yu ◽  
Huirong Sun ◽  
Wenliang Zha ◽  
Weili Cui ◽  
Ling Xu ◽  
...  

Treatment with Adriamycin (ADR) is one of the major causes of chemotherapy-induced cardiotoxicity and therefore is the principal limiting factor in the effectiveness of chemotherapy for cancer patients. Apigenin (API) has been shown to play a cardioprotective role. The present study examined the effect of API on ADR-induced cardiotoxicity in mice. Sixty male Kunming mice were randomly divided into 4 groups: a control group, ADR model group, low-dose API treatment group (125 mg·kg−1), and high-dose API treatment group (250 mg·kg−1). Blood samples were taken to evaluate a spectrum of myocardial enzymes. Cardiomyocyte apoptosis was measured using a TUNEL assay, and cardiomyocyte autophagy was observed using electron microscopy. Moreover, apoptosis-related proteins, such as Bax and Bcl-2, autophagy-related proteins, including Beclin1 and LC3B, and PI3K/AKT/mTOR pathway-related proteins were examined with western blot. Our results demonstrate that ADR caused an increase in the serum levels of cardiac injury markers and enhanced cardiomyocyte apoptosis and autophagy. API administration prevented the effects associated with ADR-induced cardiotoxicity in mice and inhibited ADR-induced apoptosis and autophagy. API also promoted PI3K/AKT/mTOR pathway activity in ADR-treated mice. In conclusion, API may have a protective effect against ADR-induced cardiotoxicity by inhibiting apoptosis and autophagy via activation of the PI3K/AKT/mTOR pathway.

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaoxue Yu ◽  
Yang Ruan ◽  
Tao Shen ◽  
Quan Qiu ◽  
Mingjing Yan ◽  
...  

The usage of doxorubicin is hampered by its life-threatening cardiotoxicity in clinical practice. Dexrazoxane is the only cardioprotective medicine approved by the FDA for preventing doxorubicin-induced cardiac toxicity. Nevertheless, the mechanism of dexrazoxane is incompletely understood. The aim of our study is to investigate the possible molecular mechanism of dexrazoxane against doxorubicin-induced cardiotoxicity. We established a doxorubicin-induced mouse and cardiomyocyte injury model. Male C57BL/6J mice were randomly distributed into a control group (Con), a doxorubicin treatment group (DOX), a doxorubicin plus dexrazoxane treatment group (DOX+DEX), and a dexrazoxane treatment group (DEX). Echocardiography and histology analyses were performed to evaluate heart function and structure. DNA laddering, qRT-PCR, and Western blot were performed on DOX-treated cardiomyocytes with/without DEX treatment in vitro. Cardiomyocytes were then transfected with miR-17-5p mimics or inhibitors in order to analyze its downstream target. Our results demonstrated that dexrazoxane has a potent effect on preventing cardiac injury induced by doxorubicin in vivo and in vitro by reducing cardiomyocyte apoptosis. MicroRNA plays an important role in cardiovascular diseases. Our data revealed that dexrazoxane could upregulate the expression of miR-17-5p, which plays a cytoprotective role in response to hypoxia by regulating cell apoptosis. Furthermore, the miRNA and protein analysis revealed that miR-17-5p significantly attenuated phosphatase and tensin homolog (PTEN) expression in cardiomyocytes exposed to doxorubicin. Taken together, dexrazoxane might exert a cardioprotective effect against doxorubicin-induced cardiomyocyte apoptosis by regulating the expression of miR-17-5p/PTEN cascade.


2022 ◽  
Vol 12 (5) ◽  
pp. 947-952
Author(s):  
Jun Zhang ◽  
Yuying Gao ◽  
Peng Chen ◽  
Yu Zhou ◽  
Sheng Guo ◽  
...  

This study was to explore the mechanism by how exosomes (exo) derived from BMSCs affects cardiomyocyte apoptosis. BMSCs were isolated and incubated with cardiomyocytes while the cardiomyocytes were exposed to sevoflurane or DMSO treatment. Apoptotic cells were calculated and level of apoptosis related proteins was detected by Western blot. Through transfection with microRNA-(miRNA)-312 inhibitor, we evaluated the effect of BMSC-exo on the sevoflurane-induced apoptosis. Sevoflurane significantly inhibited the viability of cardiomyocytes and induced cardiomyocyte apoptosis. Besides, sevoflurane decreased the expression of miR-312 and enhanced Bax expression in cardiomyocytes through restraining the phosphorylation of MAPK/ERK. Treatment with BMSC-exo, however, activated MAPK/ERK signaling by up-regulating miR-312, thereby inhibiting cardiomyocyte apoptosis, promoting cardiomyocyte proliferation, and elevating the level of Bcl-2. In conclusion, BMSC-exo-derived miR-312 inhibits sevoflurane-induced cardiomyocyte apoptosis by activating PI3K/AKT signaling pathway.


2018 ◽  
Vol 5 (1) ◽  
pp. 58
Author(s):  
Noer Kumala Indahsari ◽  
Masfufatun Masfufatun ◽  
Emilia Devi D.R

Moringa Oleifera is a plant that contains chemical compounds that are useful, such as flavonoids. The ability of this flavonoid compound that can capture free radicals cause damage and hepatoprotektan hepar. Purpose of study was to determined levels of Moringa leaf extract which can overcome the effects of liver damage caused by toxic doses of paracetamol through MDA, SGOT and SGPT Method used in this laboratory experimental study is a Randomized Post Test Only Control Group Design with the following stages: 1. Moringa Leaf Extraction with Ethanol 96%; Try 2.Preparasi animals, 3. Treatment of Animals Try the extract of leaves of Moringa 3 dose is: 250mg / 200BB rat (dose of A), 500mg / 200BB mice (dose B), 1000mg / 200BB mice (dose C) for 14 days in combination with paracetamol 2 g / 200BB mice, compared to the negative control group (group given just paracetamol 2 g / 200BB rat) and the positive control group (the group who were given regular feed) for 14 days.Results : turned out to be no difference in the reduction in SGOT levels are statistically significant between the negative control group with high-dose treatment group ie the dose C with =0,016 smaller than 0.05, whereas a decrease in ALT levels were significantly decreased in the treatment group high dose is the dose C with =0,009 smaller than 0.05. While MDA group treated with the negative control group experienced an overall decline for the dose A with =0,05, dose B with =0,0011 and dose C with =0,001. Conclusion of this study showed that the extract of Moringa leaves can be potentially as an antioxidant in all doses at once can be as hepatoprotektor at high doses is 1000mg / 200BB Rattus Novergicus.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A A Momtazi-Borojeni ◽  
M Banach ◽  
M Majeed ◽  
A Sahebkar

Abstract Background and purpose The present study was aimed to evaluate lipid-lowering and anti-atherogenic effect of an intravenous (IV) curcumin in the rabbit fed high cholesterol diet (HCD). Methods New Zealand white male rabbits (4–6 months old, n=25, weight 2.286±0.256 kg)were fed on a normal chow enriched with 0.5% (w/w) cholesterol for 5 weeks. Atherosclerotic rabbits were randomly divided into three group, including a control group receiving intravenous (IV) injection of saline buffer, two treatment groups receiving IV injection of curcumin at two different dosages, 1and 10 mg/kg/week, for 4 weeks. Blood samples were collected from fasted rabbits at pre- (week 5) and post-treatment (week 11) points for analysis of serum lipid levels, including low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglyceride (TG), and total cholesterol (TC). Aortic arch atherosclerotic lesions were assessed using hematoxylin and eosin (H&E) staining. Results To evaluate curcumin's effects on the hyperlipidemic states and atherosclerosis plaque, HCD-fed rabbits were weekly treated with the injectable curcumin at the low (1mg/kg/week) and high (10 mg/kg/week) doses by 4 weeks. At week 4 in compared with the control group, low-dose curcumin could reduce serum levels of LDL-c, HDL-c, TG, and TC by −6.22% ±1.77, −35.24% ±12.49, −29.84% ±10.14, −14.19% ±5.19, respectively. In the case of high-dose curcumin, serum levels of LDL-c, HDL-c, TG, and TC were changed by −44.36%±3.24, 14.05% ±6.39, −25.92% ±5.57, −56.59% ±10.22, respectively, when compared with the control group at week 4. Low-dose curcumin after 4 weeks' treatment could reduce serum levels LDL-c, HDL-c, TG, and TC up to 103±28 mg/dL, 18.33±4.66 mg/dL, 97.5±31 mg/dL, and 356.5±19.5 mg/dL, respectively, when compared with the base line levels (week 0). High-dose curcumin after 4 weeks' treatment could decrease serum levels of LDL-c, HDL-c, TG, HDL-c, and TC up to 207±17.04 mg/dL, 15.5±0.5 mg/dL, 333±40 mg/dL, and 514.5±22.23 mg/dL, respectively (Figure). H&E staining declared that atherosclerotic lesion grades were significantly lower in the curcumin-treated groups than the control group. Changes of lipids in rabbits on curcumin Conclusions The injectable curcumin at the low (1mg/kg) and high (10 mg/kg) could significantly improve dyslipidemia and alleviate atherosclerotic lesion in HCD-induced atherosclerotic rabbits.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4907-4907 ◽  
Author(s):  
Monika Engelhardt ◽  
Daniel Räpple ◽  
Andreas Weis ◽  
Emanuel Bisse ◽  
Gabriele Ihorst

Abstract So far, data based on small patient (pt) population suggest that the measurement of serum FLC from MM pts undergoing high-dose chemotherapy (HDCT) with stem cell transplantation (SCT) may be a sensitive marker for monitoring therapy success and for early detection of relapse. For further evaluation of the impact of FLCs on the assessment of treatment efficacy of standard- (ST) and HDCT with SCT, we performed a prospective analysis on serial serum specimens from 86 MM and 9 control pts. Measurement of FLC concentration was performed with the commercially available Freelite™ kit (Binding Site). For statistical analysis, pts’ clinical history, age at diagnosis, sex, current state of disease, karyotype and serum parameters, such as ß2-microglobulin, calcium levels and serum creatinine were evaluated. In the control group (NHL=6, AML=1, non-hematological disease=2), median concentrations of kappa(k)- and lambda(l)- FLC were 9.8 mg/l and 12.8 mg/l, respectively, corresponding to reference intervals for healthy individuals with normal kappa(k)/lambda(l)-ratios. In MM, 40 (46.5%) pts displayed kappa(k)-FLC levels above the upper range of 19mg/l, 26 (30%) had lambda(l)-FLC levels above the upper range of 26 mg/l and 9 pts (10.4%) had both elevated kappa(k)- and lambda(l)-FLC serum levels. An abnormal kappa(k)/lambda(l)-ratio was observed in 45 (52,3%) MM pts. Pts with a known kappa(k)-paraprotein (n=58) had a median FLC kappa(k)-concentration of 38 mg/l, but lambda(l)-FLC within the normal range. For pts with a known lambda(l)-paraprotein (n=27), reciprocal findings (76.4 mg/l for lambda(l)- vs kappa(k)-FLC in the normal range) were observed. Pts with responsive disease (CR, PR and SD) had both kappa(k)- and lambda(l)- FLC levels within the normal range, whereas newly diagnosed pts (ED) and those with PD had kappa(k)- FLC levels approx. 3-times the normal range, with lambda(l)- FLC levels at the upper limit of normal. Pts receiving ST as compared with HDCT had higher FLC levels. This is also observed in pts with amyloidosis, renal impairment or PD. Our results suggest that serum FLC assay allows monitoring of the therapy response and early detection of relapse. Determination of FLCs is also important, when evaluating new therapeutic substances, and for detection of prognostic patterns for better risk-based stratification of treatment.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Siyu Tao ◽  
Xue Wang ◽  
Chenxi Liao ◽  
Yan Xiong ◽  
Jie Tang ◽  
...  

Objective. This study aims to evaluate the efficacy of moxibustion on joint swelling and pain and the levels of C-X-C motif chemokine ligand 1 (CXCL1), β-endorphin (β-EP) in serum of rheumatoid arthritis (RA) patients and to investigate the anti-inflammatory and analgesic mechanism of moxibustion on improving RA. Methods. Sixty-eight patients with RA were randomly and equally classified into the control and treatment groups. The control group was treated with routine drug therapy, while the treatment group received routine drug therapy and moxibustion. Both groups were treated for eight weeks. The symptoms and laboratory indicators of RA patients were compared in the two groups before and after intervention. Results. Sixty-one patients completed the study: four patients dropped out from the treatment group and three from the control group. Trial endpoints were change (∆) in symptoms, measured by Ritchie’s articular index (RAI), swollen joint count (SJC), and laboratory indicators, measured by the level of CXCL1, β-EP, tumor necrosis factor-a (TNF-α), and interleukin-1β (IL-1β). ∆RAI, ∆SJC, ∆CXCL1, ∆β-EP, ∆TNF-α, and ∆IL-1β in the treatment group were superior to the control group (13.50 [14.50] versus 6.00 [13.00] in ∆RAI, 4.00 [3.00] versus 2.00 [4.00] in ∆SJC, 0.04 ± 0.79 ng/mL versus -0.01 ± 0.86 ng/mL in ∆CXCL1, -2.43 [5.52] pg/mg versus -0.04 [4.09] pg/mg in ∆β-EP, 3.45 [5.90] pg/mL versus 1.55 [8.29] pg/mL in ∆TNF-α, and 6.15 ± 8.65 pg/mL versus 1.28 ± 8.51 pg/mL in ∆IL-1β; all P  < 0.05). Conclusion. Moxibustion can improve the joint swelling and pain symptoms in patients with RA, which may be related to the fact that moxibustion can reduce the release of inflammatory factors in patients with RA and downregulate the level of CXCL1 and increase the level of β-EP at the same time. This trial is registered with ChiCTR-IOR-17012282.


2013 ◽  
Vol 12 (2) ◽  
pp. 93
Author(s):  
Gh.H. Jameel

The aim of this study is investigated the causes of retardation in growth of purebred calves infected by Theileria annulata.Blood samples of infected group (treatment group) were taken once, and blood samples of the control group (clinically healthy) were taken also .Serum separation was done to two groups to determinate some blood factors levels as ferritin ,phosphorus ,glucose ,growth hormone ,total T3 and total T4.It was detected that mean values of serum Ferritin was significantly higher than the values of the control group and healthy animals.No significant effect of the infection on the phosphorus and T3 levels ,While there were significant depression in serum levels of glucose ,growth hormone and T4.


2019 ◽  
Vol 7 (1) ◽  
pp. 756-767
Author(s):  
Rois Sahidin ◽  
Untung Sudharmono

Acute hepatitis is an acute disease caused by viruses, alcohol and drugs, which is characterized by an increase in SGOT SGPT serum. The purpose of this study was to determine the effectiveness of boiled comfrey leaves (Symphytum Officinale L) levels of SGOT and SGPT serum in male wistar strain rats with acute hepatitis models. The objects in this study were 30 male Wistar strain rats aged 2-3 months with a weight of 180-200 grams. The objects were randomly divided into 3 groups: the treatment group, positive control and negative control. The treatment group and positive control group were induced paracetamol 120 mg / day orally for 7 days. Boiled water of 2.8 grams of comfrey (symphytum officinale L) leaves was given as much as 2.7 cc orally for 7 days to the treatment group. Data were analyzed with SPSS version 24, one way ANOVA test was performed to compare serum levels of SGOT & SGPT. The results showed there were significant differences in serum levels of SGOT between the treatment group, positive control and negative control (p <0.05) and there were significant differences in SGPT results between the treatment group and positive control group (p <0.05) but there were no significant differences between the SGPT levels of the treatment group and the negative control group (p = 0.173). As Conclusion, boiled Comfrey leaf has an effect in decreasing serum SGOT & SGPT in male wistar strain rats with acute hepatitis model.


2018 ◽  
Vol 7 (2) ◽  
pp. 202
Author(s):  
Olivia Herliani

In diabetes mellitus there is an increase in oxidative stress in which oxidants exceed the antioxidant system resulting from the production of oxidant-antioxidant imbalance and/or limited antioxidant defenses. Abelmoschus esculentus (“okra”) is known as lowering blood glucose vegetable by Indonesian. A. esculentus has a high antioxidant activity that can: 1) lower H2O2 level; 2) decrease the amount of ROS; 3) lower •OH level. This study tried to prove that administration of A. esculentus may decrease fasting blood glucose, serum malondialdehyde, and increase superoxide dismutase activity of diabetic male white rats. This research is a pure experimental research, with randomized post test only control group designs, held in 28 days. Thirty one rats were divided into 4 groups randomly: KN = normal control group given 0.1% Na-CMC solution; KDM = DM control group injected with STZ, followed by 0.1% Na-CMC solution; P1 = treatment group 1 injected with STZ, followed by administration of A. esculentus at a dose of 775 mg/kgBW/day; P2 = treatment group 2 injected with STZ, followed by administration of A. esculentus at a dose of 1550 mg/kgBW/day. The result: administration of A. esculentus at doses of 775 mg/kgBW/day and 1550 mg/kgBW/day can not decrease fasting blood glucose and MDA serum level of diabetic male white rats. Giving A. esculentus at a dose of 1550 mg/kgBW/day may increase the activity of SOD erythrocytes of diabetic male white rats.. Conclusions: A. esculentus has the potential to lower blood glucose and MDA serum levels, also increase erythrocyte SOD activity.


2018 ◽  
Vol 6 (2) ◽  
pp. 272
Author(s):  
Niki Niki Rahmawati ◽  
Sugiyanta Sugiyanta ◽  
Elly Nurus Sakinah

  High dose of paracetamol is metabolized by cytochrome P-450 become free radical N-acetyl-p-benzoquinoneimine (NAPQI) but liver Glutathione (GSH) is not adequate to change it become nonreactive metabolite so that NAPQI bind to unsaturated fatty acid of cell membrane, causing lipid peroxidation and increase liver Malondialdehyde (MDA). 'A' apple vinegar contains anthocyanin with an antioxidant effect by electron donor to NAPQI and acetic acid to improve liver GSH level. The aim of research was to investigate the effect of 'A' apple vinegar on the rat liver MDA induced by toxic dose of paracetamol. Research groups consist of normal control (CMC Na 1% 1 ml for 14 days), negative control (CMC Na 1% 1ml for 14 days + paracetamol 291.6 mg/200gBW on the day 12nd,13rd,14th), and treatment group ('A' apple vinegar 0.4 ml/150gBW for 14 days + paracetamol 291.6 mg/200gBW on the day 12nd,13rd,14th). Liver MDA was measured on the day 15th with competitive ELISA. The average of normal control group was 21.58 ng/ml, negative control group was 70,71 ng/ml, treatment group was 37,67 ng/ml. One way ANOVA and Post hoc LSD test showed significantly differences between all groups (p<0,05). It can be concluded that 'A' apple vinegar had an effect on the liver MDA induced by toxic dose of paracetamol.   Keywords: Paracetamol, NAPQI, MDA, 'A' apple vinegar, antioxidant  


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