scholarly journals Anti-Inflammatory and Antioxidative Effects of Sumatriptan Against Doxorubicin-Induced Cardiotoxicity in Rat

2021 ◽  
Author(s):  
Mohammad Sheibani ◽  
Hedyeh Faghir-Ghanesefat ◽  
Yaser Azizi ◽  
Tahmineh Mokhtari ◽  
Hasan Yousefi‐Manesh ◽  
...  

The clinical use of doxorubicin as a potent chemotherapeutic agent is limited due to its dose-dependent cardiotoxicity. Oxidative stress and inflammatory pathways have a pivotal role in doxorubicin-induced cardiotoxicity. Sumatriptan, a 5-hydroxytryptamine (5-HT)1B/1D agonist that is mainly used to relieve migraine pain, has suggested exerting protective effects in numerous pathological conditions through antiinflammatory properties. The aim of the present study was to investigate the effects of sumatriptan on doxorubicin-induced cardiotoxicity and the contribution of anti-inflammation and antioxidative responses. Cardiotoxicity was induced by the administration of doxorubicin three times a week (2.5 mg/kg i.p) for two consecutive weeks on male rats. The animals were divided into four groups, including Control, Sumatriptan (0.1 mg/kg) received group, doxorubicin received group, and Doxorubicin+Sumatriptan (0.1 mg/kg) received group. Sumatriptan was administered 30 min before every injection of doxorubicin. On the last day of the second week, the body weight, mortality rate, electrocardiogram (ECG) and histopathological changes, cardiac inotropic study, and biochemical factors were evaluated. The loss of body weight, mortality rate, ECG parameters, reduction of papillary muscle contractility force as well as histopathological scores following administration of doxorubicin indicated severe cardiac damage. However, treatment with sumatriptan inhibited the functional and structural impairment induced by doxorubicin. In addition, sumatriptan could significantly reduce cardiac tissue levels of malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α), which were increased in the doxorubicin-treated rats. This study illustrated the protective effects of sumatriptan on decreasing doxorubicin-induced cardiac toxicity and mortality rate in part through inhibition of inflammatory and oxidative stress pathways.

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 39
Author(s):  
Ayed A. Shati ◽  
Mohamed Samir A. Zaki ◽  
Youssef A. Alqahtani ◽  
Mohamed A. Haidara ◽  
Mubarak Al-Shraim ◽  
...  

Insecticides and toxicants abound in nature, posing a health risk to humans. Concurrent exposure to many environmental contaminants has been demonstrated to harm myocardial performance and reduce cardiac oxidative stress. The purpose of this research was to study the protective effect of vitamin C (Vit C) on quinalphos (QP)-induced cardiac tissue damage in rats. Eighteen albino male rats were randomly categorised into three groups (n = 6). Control, QP group: rats received distilled water. QP insecticide treatment: an oral administration of QP incorporated in drinking water. QP + Vit C group: rats received QP and Vit C. All the experiments were conducted for ten days. Decline of cardiac antioxidant biomarkers catalase (CAT) and reduced glutathione (GPx) along with increased proinflammatory markers tumour necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) indicated oxidative and inflammatory damage to the heart following administration of QP when compared to control rats. The light microscopic and ultrastructure appearance of QP-treated cardiomyocytes exhibited cardiac damage. Administration of Vit C showed decreased oxidative and inflammatory biomarkers, confirmed with histological and electron microscopic examination. In conclusion, Vit C protected the heart from QP-induced cardiac damage due to decreased inflammation and oxidative stress.


2003 ◽  
Vol 285 (2) ◽  
pp. H499-H506 ◽  
Author(s):  
Stéphanie Héon ◽  
Martin Bernier ◽  
Nicolas Servant ◽  
Stevan Dostanic ◽  
Chunlei Wang ◽  
...  

Doxorubicin (DOX), an anticancer drug, causes a dose-dependent cardiotoxicity. Some evidence suggests that female children have an increased risk for DOX-mediated cardiac damage. To determine whether the iron chelator dexrazoxane (DXR) could reduce DOX-induced cardiotoxicity in the young, we injected day 10 neonate female and male rat pups with a single dose of saline or DOX, DXR, or DXR + DOX (20:1). We followed body weight gain with growth, measured cardiac hypertrophy after a 2-wk swim exercise program, markers of apoptosis (Bcl-2, BAX, BNIP1, caspase 3 activation), oxidative stress (heme oxygenase 1, protein carbonyl levels), the chaperone protein clusterin, and the transcriptional activator early growth response gene-1 (Egr-1) in hearts of nonexercised and exercised rats on neonate day 38. All DOX-alone and DXR + DOX-treated rats showed decreased weight gain, with female rats affected earlier than male rats. DXR-alone, DOX-alone, and DXR + DOX-treated rats had an increased heart weight-to-body weight (heart wt/body wt) ratio after the exercise program with female rats showing the largest increase in heart wt/body wt. Drug-treated females also showed increased cardiac apoptosis, as measured by the increased expression of the proapoptotic proteins BAX and BNIP1 and the appearance of caspase 3 activation products, and oxidative stress, as measured by increased heme oxygenase 1 expression, and reduced Egr-1 and clusterin expression when compared with the similarly treated male rats. We conclude that DXR preinjection did not reduce DOX-induced noncardiac and cardiac damage and that young female rats were more susceptible to DXR and DOX toxicities than age-matched male rats.


Author(s):  
Cristina Bidian ◽  
Daniela-Rodica Mitrea ◽  
Olivia Gabriela Vasile ◽  
Adriana Filip ◽  
Adriana Florinela Cătoi ◽  
...  

Background. The inflammatory mechanisms occur with the highest prevalence in pulmonary pathology. In pharmaceutical industry, carrageenan is used as a pro-inflammatory agent when the activity of anti-inflammatory agents is tested. The oxidative stress represents the imbalance between pro-oxidants and antioxidants which can lead to the activation of the oxidative mechanisms with noxius potential to the body. In experimental studies, quercetin is the most active flavonoid, having the highest anti-inflammatory and antioxidant effects. Curcumin has antioxidant effects that are similar to those of the standard antioxidants and exerts direct anti-inflammatory activity. Aims. The aim of this study is to determine the antioxidant effects of quercetin and curcumin on a carrageenan-induced pleural inflammation. Methods. Eight groups of adult male rats were used: Ia and Ib -control groups, IIa and IIb -with carrageenan administration, IIIa and IIIb -with curcumin and carrageenan, IVa and IVb -with quercetin and carrageenan administration. Blood and lung samples were taken at 4 hours (Ia, IIa, IIIa, IVa groups) and at 24 hours (Ib, IIb, IIIb, IVb groups) after carrageenan administration. Results. In serum, at 4 and at 24 hours, curcumin and quercetin showed protective effects, reducing the oxidative stress (malondialdehyde significantly decreased) and stimulating the antioxidant protection (ceruloplasmin and glutathione significantly increased) in rats with administration of these substances, in comparison to the group that received only carrageenan. In the lungs, at 4 hours, the oxidative stress was significantly reduced only in the rats that received quercetin (malondialdehyde significantly decreased), modifications that were not observed at 24 hours.     Conclusions. In serum, curcumin presented higher antioxidant effects, compared to quercetin. In lungs, quercetin administration showed superior beneficial effects, but only temporarily.


2021 ◽  
Vol 65 (1) ◽  
pp. 45-49
Author(s):  
Valery N. Rakitskii ◽  
Elena G. Chkhvirkiya ◽  
Tatiana M. Epishina

Introduction. Entering the body in various ways, pesticides, being biologically highly active compounds, can pose a real danger to public health, causing changes in non-specific biochemical reactions of metabolism occurring in all living cells. The antioxidant system, represented as a balance of lipid peroxidation and antioxidant protection (POL - AOZ), is one of the metabolic regulatory mechanisms of these responses. The aim of the study was to study the effect of a technical product (TP), a derivative of triazoles, on the acti-vity of antioxidant enzymes in the rat body, under its repeated oral intake in a chronic 12-month experiment. Material and methods. A chronic (12 months) experiment was performed on male rats with a bodyweight of 200-210 g at the beginning of the study. Tested doses: 5.0, 16.0 and 55.0 mg/kg of body weight (1 control and 3 experimental groups, 20 individuals each). In the dynamics of the experiment, after 1, 3, 6 and 12 months, the state and behavior of animals, water and food consumption were observed. Changes in the enzymatic indices of the body’s antioxidant defense system (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) were registered. Results. It was found that TP at a dose of 5.0 mg/kg of body weight does not cause significant changes in the activity of antioxidant enzymes, doses of 16.0 and 55.0 mg/kg of body weight cause an increase in the activity of superoxide dismutase (SOD) and a decrease in the activity of catalase in the body of experimental animals compared to control animals. Discussion. In the conducted chronic experiment, it was found that the studied TP at a dose of 5.0 mg/kg of body weight does not cause significant changes in the activity of the studied antioxidant enzymes in the body of rats. The introduction of TP at doses of 16.0 and 55.0 mg/kg of body weight causes a significant change in the activity of such antioxidant enzymes as SOD and catalase. Our results are consistent with the literature data, according to which the cell quickly reacts to oxidative stress by increasing the activity of SOD, and SOD is considered even as a stress protein synthesized in response to oxidative stress. Conclusions. The conducted research shows the feasibility of studying antioxidant enzymes’ activity in the mammalian body in sanitary and toxicological studies to increase the reliability of the developed hygienic standards of xenobiotics in environmental objects and food products.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Lian-Dong Zhang ◽  
He-Cheng Li ◽  
Tie Chong ◽  
Ming Gao ◽  
Jian Yin ◽  
...  

Di-(2-ethylhexyl) phthalate (DEHP) is the most widely used plastizer in the world and can suppress testosterone production via activation of oxidative stress. Genistein (GEN) is one of the isoflavones ingredients exhibiting weak estrogenic and potentially antioxidative effects. However, study on reproductive effects following prepubertal multiple endocrine disrupters exposure has been lacking. In this study, DEHP and GEN were administrated to prepubertal male Sprague-Dawley rats by gavage from postnatal day 22 (PND22) to PND35 with vehicle control, GEN at 50 mg/kg body weight (bw)/day (G), DEHP at 50, 150, 450 mg/kg bw/day (D50, D150, D450) and their mixture (G + D50, G + D150, G + D450). On PND90, general morphometry (body weight, AGD, organ weight, and organ coefficient), testicular redox state, and testicular histology were studied. Our results indicated that DEHP could significantly decrease sex organs weight, organ coefficient, and testicular antioxidative ability, which largely depended on the dose of DEHP. However, coadministration of GEN could partially alleviate DEHP-induced reproductive injuries via enhancement of testicular antioxidative enzymes activities, which indicates that GEN has protective effects on DEHP-induced male reproductive system damage after prepubertal exposure and GEN may have promising future in its curative antioxidative role for reproductive disorders caused by other environmental endocrine disruptors.


2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Rong Chang Chen ◽  
Xu Dong Xu ◽  
Xue Zhi Liu ◽  
Gui Bo Sun ◽  
Yin Di Zhu ◽  
...  

Doxorubicin has cardiotoxic effects that limit its clinical benefit in cancer patients. This study aims to investigate the protective effects of the total flavonoids fromClinopodium chinense(Benth.) O. Ktze (TFCC) against doxorubicin- (DOX-) induced cardiotoxicity. Male rats were intraperitoneally injected with a single dose of DOX (3 mg/kg) every 2 days for three injections. Heart samples were collected 2 weeks after the last DOX dose and then analyzed. DOX delayed body and heart growth and caused cardiac tissue injury, oxidative stress, apoptotic damage, mitochondrial dysfunction, and Bcl-2 expression disturbance. Similar experiments in H9C2 cardiomyocytes showed that doxorubicin reduced cell viability, increased ROS generation and DNA fragmentation, disrupted mitochondrial membrane potential, and induced apoptotic cell death. However, TFCC pretreatment suppressed all of these adverse effects of doxorubicin. Signal transduction studies indicated that TFCC suppressed DOX-induced overexpression of p53 and phosphorylation of JNK, p38, and ERK. Studies with LY294002 (a PI3K/AKT inhibitor) demonstrated that the mechanism of TFCC-induced cardioprotection also involves activation of PI3K/AKT. These findings indicated the potential clinical application of TFCC in preventing DOX-induced cardiac oxidative stress.


2021 ◽  
Vol 22 (6) ◽  
pp. 2867
Author(s):  
Ana Ilic ◽  
Dusan Todorovic ◽  
Slavica Mutavdzin ◽  
Novica Boricic ◽  
Biljana Bozic Nedeljkovic ◽  
...  

The possible cardioprotective effects of translocator protein (TSPO) modulation with its ligand 4′-Chlorodiazepam (4′-ClDzp) in isoprenaline (ISO)-induced rat myocardial infarction (MI) were evaluated, alone or in the presence of L-NAME. Wistar albino male rats (b.w. 200–250 g, age 6–8 weeks) were divided into 4 groups (10 per group, total number N = 40), and certain substances were applied: 1. ISO 85 mg/kg b.w. (twice), 2. ISO 85 mg/kg b.w. (twice) + L-NAME 50 mg/kg b.w., 3. ISO 85 mg/kg b.w. (twice) + 4′-ClDzp 0.5 mg/kg b.w., 4. ISO 85 mg/kg b.w. (twice) + 4′-ClDzp 0.5 mg/kg b.w. + L-NAME 50 mg/kg b.w. Blood and cardiac tissue were sampled for myocardial injury and other biochemical markers, cardiac oxidative stress, and for histopathological evaluation. The reduction of serum levels of high-sensitive cardiac troponin T hs cTnT and tumor necrosis factor alpha (TNF-α), then significantly decreased levels of serum homocysteine Hcy, urea, and creatinine, and decreased levels of myocardial injury enzymes activities superoxide dismutase (SOD) and glutathione peroxidase (GPx) as well as lower grades of cardiac ischemic changes were demonstrated in ISO-induced MI treated with 4′-ClDzp. It has been detected that co-treatment with 4′-ClDzp + L-NAME changed the number of registered parameters in comparison to 4′-ClDzp group, indicating that NO (nitric oxide) should be important in the effects of 4′-ClDzp.


2021 ◽  
pp. 096032712110134
Author(s):  
O Zouaoui ◽  
K Adouni ◽  
A Jelled ◽  
A Thouri ◽  
A Ben Chrifa ◽  
...  

Phytochemical composition and antioxidant activity of flowers decoction at post-flowering stage (F3D) of Opuntia dejecta were determined. The obtained findings demonstrate that F3D has a marked antioxidant activity in all tested assays. Furthermore, the present study was designed to test the protective activity of F3D against induced Diabetes type 2 (DT2) in male rats. Those metabolic syndromes were induced by a high-fructose diet (HFD) (10% fructose solution) for a period of 20 weeks. F3D was administered orally (100 and 300 mg/kg body weight) daily for the last 4 weeks. Metformin (150 mg/kg body weight) was used as a standard drug and administrated orally for the last 4 weeks. The results showed a significant increase in blood glucose, triglycerides and hepatic markers (ALAT, ASAT and ALK-P) in HFD group. A significant increase in hepatic TBARS and a significant decrease in SOD, CAT and GPX were observed in fructose fed rats compared to control group. Administration of F3D showed a protective effect in biochemical and oxidative stress parameters measured in this study. Also, oral administration of F3D restored the histological architecture of rat liver in comparison with rats fed HFD. In conclusion, F3D attenuated hepatic oxidative stress in fructose-fed rats.


Author(s):  
Gabriel O. Oludare ◽  
Gbenga O. Afolayan ◽  
Ganbotei G. Semidara

Abstract Objectives This study aimed to access the protective effects of d-ribose-l-cysteine (DRLC) on cyclophosphamide (CPA) induced gonadal toxicity in male rats. Methods Forty-eight male Sprague-Dawley rats were divided into six groups of eight rats each. Group I the control, received distilled water (10 ml/kg), Group II received a single dose of CPA 100 mg/kg body weight intraperitoneally (i.p), Groups III and IV received a single dose of CPA at 100 mg/kg (i.p) and then were treated with DRLC at 200 mg/kg bodyweight (b.w) and 400 mg/kg b.w for 10 days, respectively. Rats in Groups V and VI received DRLC at 200 and 400 mg/kg b.w for 10 days, respectively. DRLC was administered orally. Results Results showed that CPA increased percentage of abnormal sperm cells and reduced body weight, sperm count, sperm motility, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels (p<0.05). CPA also induced oxidative stress as indicated by the increased malondialdehyde (MDA) content and reduced activities of the oxidative enzymes measured (p<0.05). Liver enzymes were elevated while the blood cells production was decreased in the rats administered CPA. DRLC supplementation enhanced the antioxidant defence system as indicated in the reduced MDA levels and increased activities of the antioxidant enzymes when compared with CPA (p<0.05). Bodyweight, sperm count, sperm motility, FSH, and testosterone levels were increased in the CPA + DRLC II group compared with CPA (p<0.05). Conclusions The results of this present study showed that DRLC has a potential protective effect on CPA-induced gonadotoxicity.


2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Tai-Yuan Chuang ◽  
Chia-Ying Lien ◽  
Chih-Hsiang Hsu ◽  
Chen-Wen Lu ◽  
Chung-Hsin Wu

Hypothyroidism frequently causes cardiopulmonary dysfunction, such as heart failure and respiratory and metabolic deficiencies. This study investigated the effects of Chinese herbal formula B307 on thyroidectomy-induced cardiopulmonary exercise dysfunction in rats. Twenty male rats were equally divided into four groups: negative control with sham treatment, positive control with oral B307 treatment only, thyroidectomy treatment only, and thyroidectomy with B307 posttreatment groups. The feeding dose of B307 was 50 mg/kg per day for 14 days. We examined and then compared the thyroid-stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine (T4), and reactive oxygen species (ROS) from the blood of these four groups. Also, we compared the body weight, neck subcutaneous blood flow, cardiac ejection function, cardiopulmonary exercise function of oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory quotient (RQ = VCO2/VO2) among the four groups. Our results indicated that thyroidectomized rats had significantly decreased body weight, neck subcutaneous blood flow, cardiac ejection function, serum T3 and T4, and VO2 and VCO2, but had significantly increased ROS and TSH levels and RQ values compared with sham rats (P<0.01–0.05). In addition, thyroidectomized rats receiving oral B307 treatment had significantly increased body weight, neck subcutaneous blood flow, cardiac ejection function, and VO2, but significantly decreased ROS and TSH levels and VCO2 and RQ values compared with thyroidectomized rats (P<0.01–0.05). We suggest that the B307 could be a protective and beneficial alternative treatment for thyroidectomy-induced cardiopulmonary exercise dysfunction.


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