Cardiotoxicity In Wistar Rats Research Articles

Elucidation of the Possible Molecular Mechanism for the Anti-Apoptotic Ef-fect of Terpene-Rich Extract of Amomum subulatum and Coriandrum sa-tivum against Rodent Model of Cardiotoxicity

Background: Spices, including Amomum subulatum and Coriander sativum, are not only popular for improving food flavour but are also accepted worldwide for their health benefits in various disorders. background: Spices including Amomim subulatum and Coriander sativum are not only popular to improve food flavour but also worldwide accepted for their health benefits in various disorders to preventive and curative importance. Objective: This study aimed to elucidate the possible mechanism for the anti-apoptotic effect of terpene-rich extract of Amomum subulatum and Coriandrum sativum against the rodent model of cardiotoxicity. Methods: Effects of standardized terpenoids-rich aqueous methanolic extract of two commonly used spices, viz. Amomum subulatum Roxb. and Coriandrum sativum Linn., were investigated on doxorubicin-induced apoptotic changes and cardiotoxicity in Wistar rats with the aim of in-vestigating the mechanism. Prior to the in vivo experiment, the extracts were subjected to quan-titative estimation of possible bioactive markers of the terpenes by employing a newly devel-oped, optimized, and validated GC-MS method along with TLC profiling. Results: Cardiotoxicity was evident from elevated creatinine kinase (CK-MB), lactate dehydro-genase (LDH), and malondialdehyde (MDA) levels in the toxic control group after treatment with doxorubicin (2.5mg/kg i.p. given twice a week for three weeks). Caspase-3, Tumor necrosis factor-α (TNF-α), and Interleukin-6 (IL-6) were also induced in animals treated with doxorubi-cin. Treatment with Amomum subulatum and Coriandrum sativum at the doses of 100 and 200mg/kg exhibited significant (P<0.001) reversal of CK-MB, LDH, MDA, Caspase-3, TNF-α, and IL-6 levels. This protective effect was further supported by the results of DNA gel electro-phoresis and histopathological observations. Conclusion: This study supports the cardioprotective role of selected spices against doxorubicin-induced cardiotoxicity through the anti-apoptotic mechanism.

Ginkgo biloba supplement modulates mTOR/ERK1/2 activities to mediate cardio-protection in cyclosporin-A-induced cardiotoxicity in Wistar rats

BackgroundCyclosporine-A (Cs-A), an immunosuppressant drug indicated for organ transplant patients has been associated with toxicities arising from activation of pathological signalling. Meanwhile Ginkgo biloba supplement (GBS) is an antioxidant-enhancing herbal product widely used for treating neurological and vascular dysfunctions. ObjectivesThis study investigated the ameliorative effect of GBS on cyclosporine-A induced cardiotoxicity in Wistar rats. MethodsThe study included 20 Wistar rats (n = 5) and they were treated as follows: group 1 received distilled water (10 mL/kg), group 2 received Cs-A (25 mg/kg), group 3 received GBS (50 mg/kg) and group 4 received Cs-A (25 mg/kg) and GBS (50 mg/kg). All treatment were done intraperitoneal for 14 days and thereafter, animals were euthanised and heart tissues were harvested for biochemical assays as well as immunohistochemical studies. Blood was also collected for serum biochemical studies. ResultsOur results revealed that GBS reduces Cs-A induced increase of AST, ALT, ALP, LDH, and GGT levels in serum relative to Cs-A group. Also, increased oxido-nitrergic markers like MDA, NO, together with elevated concentrations of cholesterol, triglycerides, LDL, creatine kinase-MB, troponin-I, as well as pro-inflammatory cytokines (IL-6, and TNF-α) and heart weight index were reduced by GBS. The Cs-A induced suppression of low-density lipoprotein, antioxidant (GSH, SOD, CAT), Na-K ATPase activities and antiapoptotic element, Bcl-2 were increased by GBS. Additionally, signalling pathways including ERK1/2, and mTOR as well as ventricular thickness were significantly alleviated by GBS treatment. ConclusionThe findings suggest that GBS ameliorated Cs-A-induced cardiotoxicity by activating mTOR/ERK1/2 signalling pathways.

Anti-apoptotic and antioxidant mechanisms may underlie the abrogative potential of Ocimum gratissimum Linn. Leaf extract and fractions against trastuzumab-induced cardiotoxicity in Wistar rats

Clinical use of trastuzumab (TZM), has been widely associated with increased incidence of cardiotoxicity. Ocimum gratissimum Linn. is a household medicinal plant popularly used for treating inflammatory conditions. In this study, we investigated the abrogative potential of 100 mg/kg/day of the ethanol leaf extract of Ocimum gratissimum Linn. (OG) and its petroleum ether (PEOG), ethyl acetate (EAOG) and ethanol (EOG) fractions in TZM intoxicated Wistar rats for 7 days using anthropometric, biochemical, histopathological and immunohistochemical endpoints. In addition, secondary metabolite constituents in OG and its fractions were determined through Gas Chromatography-Mass Spectrometry (GC-MS). The study results showed that oral pretreatments with OG and OG fractions as well as the fixed dose valsartan-lisinopril (VAL-LSP) combination effectively ameliorated and restore nearly normal levels the TZM-altered plasma cardiac troponin I and antioxidant profile which were corroborated by histopathological and immunohistochemical findings as indicated by the inhibition of TZM-induced activation of caspases-3 and − 9 and profound upregulation of BCL-2 expression. Phytoscan of OG and its fractions showed the presence of thymol and in high amount. Overall, our findings revealed the cardioprotective potentials of OG, OG fractions and fixed dose VAL-LSP combination against TZM-induced cardiotoxicity which probably was mediated via abrogation of cardiomyocyte apoptosis and antioxidant mechanisms.

Assessment of the ameliorative potential of A. cepa and its fractions on doxorubicin-induced cardiotoxicity in Wistar rats

The assessment of the ameliorative potentials of A. cepa and its fractions on doxorubicin-induced cardiotoxicity in Wistar rats was evaluated in this study. 45 Wistar rats of both sexes were randomly divided into 9 groups of 5 animals each; as follows: group I, served as control and received 10 ml/kg body weight of 0.9% saline, group II, 10mg/kg body weight of doxorubicin, group III, 4 mg/kg body weight of vitamin E plus Dox. Group IV, 1000mg/kg body weight of crude extracts of A. cepa plus Dox. Group V, 1000mg/kg body weight of n-hexane fraction of A. cepa plus Dox. Group VI, 1000mg/kg body weight of DCM fraction of A. cepa plus Dox. Group VII, 1000mg/kg body weight of EA fraction of A.cepa plus Dox. Group VIII, 1000mg/kg body weight of methanol fraction of A. cepa plus Dox, and group IX, combinations of 1000mg/kg, 4mg/kg 10mg/kg body weight of crude extract of A. cepa, vitamin E and Dox respectively for 16 days. Groups I and II treatments lasted 14 days, while treatments for groups III-VIII lasted 16 days (making 14 day for respective treatments and addition 2 days for doxorubin administered once 48 hourly) before sacrificing. All substances in this study were administered orally except doxorubicin that was done intravenously. The results showed that doxorubicn administration (group II) significantly (p<0.05) elevated troponin and NO levels; CK and LDH activities, compared to the control group indicating cardiotoxicity. This cardiotoxic effect of doxorubincin was significantly reversed by administration of vitamin E, crude extract, DCM, n-hexane to groups III, IV, V and VI respectively. A significant (p<0.05) reduction of only NO was recorded with EA fraction, compared with group II (dox). Methanol fraction (group VIII) further escalated doxorubicin-induced cardiotoxicity with a significantly (p<0.05) elevated myoglobulin and NO levels and CK activity. But the combined treatment with vitamin E, Crude extract and dox significantly (p<0.05) reduced cardiotoxic markers in this study except myoglobulin where a significant (p<0.05) elevation was recorded. It can be concluded that fresh A. cepa leaves extract possesses cardio-protective properties and may be a suitable cardio-protector against drug-induced cardiotoxicity in crude extract form, fractions of DCM and n-hexane but definitely not with methanol fraction as shown in this study.

Deciphering the Ameliorative Potential of 5, 7-dihydroxyflavone (Chrysin) on Doxorubicin-Induced Cardiotoxicity by Modulating Oxidative Stress in Rats

Doxorubicin-induced cardiotoxicity is the leading cause of morbidity and mortality among cancer survivors. The present study aimed to investigate the ameliorative effect of 5, 7-dihydroxyflavone (chrysin) against doxorubicin-induced cardiotoxicity in Wistar rats. Thirty-five adult male Wistar albino rats were randomly allocated into seven groups (n = 5 each) which consisted of normal control (group 1) receiving phosphate buffer saline (0.4 ml), positive control (Group 2) received 2mg\kg of doxorubicin (DOX) through an intraperitoneal route once weekly for 21 days, chrysin low dose and chrysin high dose (Group 3 and 4) received oral administration of chrysin 50&100mg/kg for 21 days, chrysin low dose and DOX, chrysin medium dose and DOX and chrysin high dose and DOX(group 5, 6, and 7) received 2mg/kg of DOX once weekly with 50, 100 and 150mg/kg of chrysin for 21 days. Significant elevations in cardiac troponin I (cTnI) and histological lesions, which corresponded with oxidative stress, inflammation, apoptotic indicators, and cardiotoxicity when compared to controls, were indicative of DOX-induced cardiotoxicity. Malondialdehyde (MDA), a sign of oxidative stress, SOD, CPK (creatinine phosphokinase), TBARS (thiobarbituric acid reactive substance), and CAT (catalase) were also elevated in the DOX group. The DOX group also had increased levels of cardiac inflammatory markers, including as interleukin-1 (IL-1), interleukin-6 (IL-6), and the apoptotic marker caspase-3. 5, 7-dihydroxyflavone (chrysin) significantly mitigated, but did not entirely reverse, the cardiotoxicity caused by DOX by reducing the histopathological scores of cardiomyopathies and lowering cTnI in comparison to the DOX group. Additionally, chrysin reduced MDA to substantially similar levels as the control. Following chrysin administration, significant decreases in IL-1, IL-6, and caspase-3 were also seen in comparison to the DOX-only group. All things considered, these findings point to chrysin's protective action against DOX-induced cardiotoxicity, which may have been rendered possible by oxidative stress, inflammatory, and apoptotic suppression.

Cardioprotective effects of Rhododendron arboreum leaf extract against Doxorubicin-induced cardiotoxicity in Wistar rats by modulating electrocardiographic and cardiac biomarkers

BackgroundCardiotoxicity and related complications are well-known adverse effects of anticancer drugs like doxorubicin (DOX). A medicinal plant called Rhododendron arboreum is used by traditional healers of Sikkim in the treatment of heart ailments and has also been reported for widespread therapeutic effects in many clinical studies. Thus the present study has been designed to evaluate the protective effects of Rhododendron arboreum leaf extract (RALE) against DOX-induced cardiotoxicities.MethodsCommencement of research with the collection of the Rhododendron arboreum leaves and drying it in the shade, the extraction was performed using the Soxhlet method with an ethanolic solvent. The phytoconstituents of the RALE were then quantified and qualitatively evaluated. Doxorubicin-induced cardiotoxicity was carried out using four groups consisting of six animals each. Doxorubicin was administered with a dose of 3 mg/kg injected intraperitoneally (i.p.) on the 1st,7th,14th,21st and 28th day of cumulative dose of 15 mg/kg throughout the experimental period with RALE treatment (250 mg/kg and 100 mg/kg) orally for 28 days. The influence of the treatment was analyzed by quantification of cardiac biomarkers and electrocardiographic method.ResultsThe serum levels of cardiac biomarkers such as Lactate Dehydrogenase (LDH), Creatine kinase-N-acetyltransferase (CK-NAC), Creatine kinase-MB (CK-MB), Aspartate Transaminase (AST), Alanine Transaminase (ALT), which were elevated due to DOX-induced cardiotoxicity were significantly reduced in all RALE (250 mg/kg and 100 mg/kg) treated groups. Similarly, the electrocardiographic changes like prolonged QT interval, widening of QRS complex amplitude, undefined ST segment, arrhythmias and increased heart rate were also restored close to normal in all treated groups compared to the DOX control group.ConclusionFollowing the data observed during the study, results reported that R. arboreum possesses the free radical scavenging property, improved cardiotoxic laboratory parameters and restored reversible cellular injury due to existing of the principle constituent’s impact on proinflammatory mediators.

3-Indolepropionic acid mitigates sub-acute toxicity in the cardiomyocytes of epirubicin-treated female rats.

Epirubicin (EPI) is an effective chemotherapeutic against breast cancer, though EPI-related cardiotoxicity limits its usage. Endogenously derived 3-indolepropionic acid (3-IPA) from tryptophan metabolism is of interest due to its antioxidant capabilities which may have cardioprotective effects. Supplementation with 3-IPA may abate EPI's cardiotoxicity, and herein we studied the possibility of lessening EPI-induced cardiotoxicity in Wistar rats. Experimental rats (n = 30; BW 180-200g) were randomly distributed in five cohorts (A-E; n = 6 each). Group A (control), Group B (EPI 2.5mg/mL), and group C (3-IPA 40mg/kg) while Groups D and E were co-treated with EPI (2.5mg/mL) together with 3-IPA (D: 20 and E: 40mg/kg). Following sacrifice, oxidative status, lipid profile, transaminases relevant to cardiac function, and inflammatory biomarkers were analysed. Also, 8-hydroxyl-2'-deoxyguanosine (8-OHdG) and cardiac troponin T (cTnT) levels were assessed using an enzyme-linked immunosorbent assay (ELISA). EPI-initiated increases in cardiotoxicity biomarkers were significantly (p < 0.05) reduced by 3-IPA supplementation. Decreased antioxidant and increases in reactive oxygen and nitrogen species (RONS), 8-OHdG and lipid peroxidation were lessened (p < 0.05) in rat hearts co-treated with 3-IPA. EPI-induced increases in nitric oxide and myeloperoxidase were reduced (p < 0.05) by 3-IPA co-treatment. In addition, 3-IPA reversed EPI-mediated alterations in alanine aminotransferase (ALT), aspartate amino transaminases (AST), lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and serum lipid profile including total cholesterol and triglycerides. Microscopic examination of the cardiac tissues showed that histopathological lesions severity induced by EPI was lesser in 3-IPA co-treated rats. Our findings demonstrate that supplementing endogenously derived 3-IPA can enhance antioxidant protection in the cardiac tissue susceptible to EPI toxicity in female rats. These findings may benefit breast cancer patients undergoing chemotherapy by further validating these experimental data.

Attenuation of Doxorubicin Induced Cardiotoxicity in Wistar Rats by Extracts of Fruits of &lt;i&gt;Ziziphus jujuba&lt;/i&gt; Lam

The objective of the study was to evaluate the cardioprotective activity of fruits of Ziziphus jujuba Lam. in doxorubicin induced cardiotoxicity in Wistar rats. The ethanolic and aqueous extract of fruits of Z. jujuba has been prepared. Male Wistar rats were divided into seven groups. Vehicle control was Group 1. Doxorubicin 5 mg/kg i.p. was administered to Group 2 animals on the 7th and 14th day. Animals in groups 3 and 4 were dosed with ethanolic extracts of 200 and 400 mg/kg p.o. while groups 5 and 6 received aqueous extracts of 200 and 400mg/kg i.p. Animals from group 7 were given nebivolol 5 mg/kg p.o. All the animals were treated for 28 days. Doxorubicin (2.5 mg/kg) was injected intraperitoneally to group 2 to group 7 on day 7th and day 14th. Body weight, ECG, blood pressure, CK-MB, Cardiac troponin-I and LDH were the study parameters. The histology of the heart was performed at the end of the study. Doxorubicin showed cardiotoxicity manifested by changes in serum marker enzymes, ECG and hemodynamic parameters which were further confirmed by histology of the heart. These changes induced by doxorubicin were attenuated by treatment with extracts of the fruit of Ziziphus jujuba Lam. It is concluded that aqueous extract of the fruit of Ziziphus jujuba Lam. (400 mg/kg p.o.) treatment for 28 days protects the heart of rats in doxorubicin induced cardiotoxicity.

Metabolite profiling and Ameliorative effect of quince (Cydonia oblonga) leaves against doxorubicin induced cardiotoxicity in Wistar rats

Quince (Cydonia oblonga) leaves are traditionally reported to alleviate the risk of cardiovascular disease. The study envisaged to explore the in vitro and in vivo phytochemical and cardio protective potential of quince extract respectively. Different solvent extracts (Aqueous, Ethanolic, Hydroethanolic, Methanolic) of quince leaf obtained via two different extraction methods (Ultrasonication and Reflux) were evaluated for the phytochemical and antioxidant analysis. Among all the extracts, quince ethanolic extract, extracted via sonication was found to have the maximum phenolics (39.89 ± 0.67 mg GAE/g DW), flavonoids (21.51 ± 1.0 mgRE/g DW) and an anti-oxidant potential 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH) with IC50 value of 168.88 ± 2.24 μg/ml. The High-performance thin layer chromatograph (HPTLC) and ultrahigh performance liquid chromatography mass spectrometry (UPLC-MS) analysis confirmed the presence of bio active compounds. Furthermore, the in vivo activity was ascertained against Doxorubicin (DOX) induced cardio toxicity in rats fed orally with the extract at 160 and 320 mg/kg body weight. The pre-treated groups significantly assuaged the changes induced by DOX in the electrocardiogram (ECG). Additionally, it mitigated the elevation in the blood serum parameters; aspartate transaminase (AST), lactate dehydrogenase (LDH), creatinine kinase-MB (CK- MB) and also repressed glutathione (GSH) depletion and rise in malondialdehyde (MDA) level induced by DOX. Furthermore, improvement in histopathological changes of the heart tissue concomitant to DOX induced toxicity was also observed such as, reduced degeneration, necrosis, inflammation and apoptosis. Thus, it could be concluded that cardioprotective activity of quince extract accredited to the occurrence of phytoconstituents prevented the DOX induced cardiotoxicity and helped to reinstate the cardiac damage in rats.

Loaded paraquaton polymeric nanocapsules and evaluation for cardiotoxicity in Wistar rats

ABSTRACT Present work was conducted to prepare and evaluate, loaded paraquat nano-hydrogels using chitosan, sodium polytriphosphate, and xanthan via ionic gelification method. The fabricated L-PQ formulations were analyzed for surface morphology and functional groups using SEM and FTIR, respectively. The stability of the synthesized nanoparticle was, also, analyzed in terms of diameter size, zeta potential, dispersion index, and pH. Furthermore, the cardiotoxicity effects of the synthesized nanogels were investigated on Wistar rats in terms of enzymatic activity, echocardiographic, and histological analysis. The proper stability of the prepared formulation was also confirmed by diameter size, zeta potential, dispersion index, and pH. The efficiency of encapsulation was about 90±3.2% and the release of PQ in the loaded nanogel was about 90±2.3%. A decrease in ST (shortening time) segment by formulated PQ, either in peritoneal or gavage exposure pathway, indicates the effectiveness of the capsule layer against the penetration of toxin into the body.

Metformin and Dapagliflozin Attenuate Doxorubicin-Induced Acute Cardiotoxicity in Wistar Rats: An Electrocardiographic, Biochemical, and Histopathological Approach

Doxorubicin is a widely used anticancer drug whose efficacy is limited due to its cardiotoxicity. There is no ideal cardioprotection available against doxorubicin-induced cardiotoxicity. This study aimed to investigate the anticipated cardioprotective potential of metformin and dapagliflozin against doxorubicin-induced acute cardiotoxicity in Wistar rats. At the beginning of the experiment, cardiac screening of experimental animals was done by recording an electrocardiogram (ECG) before allocating them into the groups. Thereafter, a total of thirty healthy adult Wistar rats (150–200 g) were randomly divided into five groups (n = 6) and treated for eight days as follows: group I (normal control), group II (doxorubicin control), group III (metformin 250 mg/kg/day), group IV (metformin 180 mg/kg/day), and group V (dapagliflozin 0.9 mg/kg/day). On the 7th day of the treatment phase, doxorubicin 20 mg/kg was administered intraperitoneal to groups II, III, IV, and V. On the 9th day (immediately after 48 h of doxorubicin administration), blood was collected from anesthetized animals for glucose, lipid profile, CK-MB & AST estimation, and ECG was recorded. Later, animals were sacrificed, and the heart was dissected for histopathological examination. We found that compared to normal control rats, CK-MB, AST, and glucose were significantly increased in doxorubicin control rats. There was a significant reversal of doxorubicin-induced hyperglycemia in the rats treated with metformin 250 mg/kg compared to doxorubicin control rats. Both metformin (180 mg/kg and 250 mg/kg) and dapagliflozin (0.9 mg/kg) significantly altered doxorubicin-induced ECG changes and reduced the levels of cardiac injury biomarkers CK-MB and AST compared to doxorubicin control rats. Metformin and dapagliflozin protected the cellular architecture of the myocardium from doxorubicin-induced myocardial injury. Current study revealed that both metformin and dapagliflozin at the FDA-recommended antidiabetic doses mitigated doxorubicin-induced acute cardiotoxicity in Wistar rats. The obtained data have opened the perspective to perform chronic studies and then to clinical studies to precisely consider metformin and dapagliflozin as potential chemoprotection in the combination of chemotherapy with doxorubicin to limit its cardiotoxicity, especially in patients with comorbid conditions like type II diabetes mellitus.

Antioxidative properties of Adansonia digitata L. (baobab) leaf extract exert protective effect on doxorubicin-induced cardiac toxicity in Wistar rats

•Doxorubicin is a standard medication utilized in therapy in cancer and its related form.•Cumulative and dose-dependent cardiac toxicity of doxorubicin (DOX) has been a major challenge in its usage.•Paucity of scientific information on medicinal value of some plants is a major concern.•Antioxidant properties of A. digitata confirm its outstanding protective role.•Properties of Adansonia digitata is based on some bioactive compounds present. ScopeDoxorubicin (DOX), for decades, is one of the most widely used and successful chemotherapeutic drug but its cumulative and dose-dependent cardiac toxicity has been the major concern of oncologists in cancer therapeutic practice.AimIn this study, the antioxidative properties of Adansonia digitata leaf extract to protect heart against doxorubicin-induced cardiotoxicity in wistar rats was evaluated.Material and MethodsThirty male wistar rats (100±0.35 g) grouped into five of six (6) each: group1 (normal control) received 0.5 mL of distilled water; group 2 received 20 mg/kg of DOX only; group3 treated with 20 mg/kg of DOX +100 mg/kg of A. digitata leaf extract; group4 received 20 mg/kg of DOX + 200 mg/kg of A. digitata leaf extract and group5 was administered 20 mg/kg of DOX+400 mg/kg of A. digitata DOX was administered subcutaneously weekly while extract was fed orally for three weeks respectively.ResultQuantitative analysis revealed some bioactive compounds: phenols, flavonoids, saponin, alkaloid and phenols (168.26±40, 26.07±0.15, 16.18±0.31 and 10.03±0.10 mg/100ml). Significant increase (P< 0.05) in Troponin T concentration was observed in group 2 against experimental groups administered A. digitata. Similarly, LDH and CK activities increased in all test groups against normal control. Decreased Troponin T, CK, and LDH concentrations were observed in rats fed 400 mg/kg against the groups pretreated with 100 mg/kg and 200 mg/kg bwt of A. digitata. MDA levels decreased significantly (P>.0.05) in the groups orally fed with the extract compared with group2. Variations of activities of SOD, CAT, and GPX were observed in the groups treated with the extracts compared with DOX induced untreated rats. Conversely, Protein concentration increased in all the test groups administered extract as against group2. Histopathological revealed infiltration of inflammatory cells and congestion in the blood vessels. Administration of the extract showed predominantly normal structure without inflammatory cell infiltration.ConclusionIt has been demonstrated that A. digitata leaf extract exert protective effects on DOX-induced cardio toxicity in wistar rats. Doxorubicin (DOX), for decades, is one of the most widely used and successful chemotherapeutic drug but its cumulative and dose-dependent cardiac toxicity has been the major concern of oncologists in cancer therapeutic practice. In this study, the antioxidative properties of Adansonia digitata leaf extract to protect heart against doxorubicin-induced cardiotoxicity in wistar rats was evaluated. Thirty male wistar rats (100±0.35 g) grouped into five of six (6) each: group1 (normal control) received 0.5 mL of distilled water; group 2 received 20 mg/kg of DOX only; group3 treated with 20 mg/kg of DOX +100 mg/kg of A. digitata leaf extract; group4 received 20 mg/kg of DOX + 200 mg/kg of A. digitata leaf extract and group5 was administered 20 mg/kg of DOX+400 mg/kg of A. digitata DOX was administered subcutaneously weekly while extract was fed orally for three weeks respectively. Quantitative analysis revealed some bioactive compounds: phenols, flavonoids, saponin, alkaloid and phenols (168.26±40, 26.07±0.15, 16.18±0.31 and 10.03±0.10 mg/100ml). Significant increase (P< 0.05) in Troponin T concentration was observed in group 2 against experimental groups administered A. digitata. Similarly, LDH and CK activities increased in all test groups against normal control. Decreased Troponin T, CK, and LDH concentrations were observed in rats fed 400 mg/kg against the groups pretreated with 100 mg/kg and 200 mg/kg bwt of A. digitata. MDA levels decreased significantly (P>.0.05) in the groups orally fed with the extract compared with group2. Variations of activities of SOD, CAT, and GPX were observed in the groups treated with the extracts compared with DOX induced untreated rats. Conversely, Protein concentration increased in all the test groups administered extract as against group2. Histopathological revealed infiltration of inflammatory cells and congestion in the blood vessels. Administration of the extract showed predominantly normal structure without inflammatory cell infiltration. It has been demonstrated that A. digitata leaf extract exert protective effects on DOX-induced cardio toxicity in wistar rats.

P-027 - Diagnostic efficacy of 68Ga-DOTAGA-Duramycin for early detection of anthracycline induced cardiotoxicity in Wistar rats

P-027 - Diagnostic efficacy of 68Ga-DOTAGA-Duramycin for early detection of anthracycline induced cardiotoxicity in Wistar rats

Therapeutic effect of methanolic leaves extract of Solanum incanum in copper induced cardio-toxicity in wistar rats

Therapeutic effect of methanolic leaves extract of Solanum incanum in copper induced cardio-toxicity in wistar rats

Nauclea orientalis (L.) Bark Extract Protects Rat Cardiomyocytes from Doxorubicin-Induced Oxidative Stress, Inflammation, Apoptosis, and DNA Fragmentation.

The therapeutic efficacy of anthracycline antibiotic, doxorubicin (Dox), is hampered due to the dose-dependent cardiotoxicity. The objective of the study was to explore the counteraction of aqueous bark extract of Nauclea orientalis in Dox-induced cardiotoxicity in Wistar rats. The acute and subchronic toxicity study performed with 2.0 g/kg of the plant extract revealed biochemical and haematological parameters to be within the physiological range, and no histological alterations were observed in any organs isolated. Screening of plant extract for the protection of the myocardium from Dox-induced oxidative stress, inflammation, and apoptosis was performed on five groups of rats: control, plant extract control, Dox control (distilled water (D.H2O) 2 weeks + on the 11th day single injection of Dox, 18 mg/kg), plant + Dox (2.0 g/kg plant extract 2 weeks + on the 11th day Dox, 18 mg/kg), and positive control, dexrazoxane. A significant increase in cardiac biomarkers and lipid peroxidation (p < 0.001) and a significant decrease in antioxidant parameters (p < 0.001) were observed in the Dox control group. All these parameters were reversed significantly (p < 0.05) in the plant-pretreated group. The histopathological assessment of myocardial damage provided supportive evidence for the biochemical results obtained. Inflammatory markers, myeloperoxidase, expression of TNFα and caspase-3, and DNA fragmentation (TUNEL positive nuclei) were significantly elevated (p < 0.05), and expression of Bcl-2 was significantly decreased (p < 0.05) in the Dox control; however, all these parameters were significantly reversed in the plant extract-treated group. In conclusion, the aqueous bark extract of Nauclea orientalis (2.0 g/kg) has the ability to attenuate the Dox-induced oxidative stress, inflammation, apoptosis, and DNA fragmentation in Wistar rats.

Therapeutic effect of methanolic leaves extract of cannabis in copper induced cardio-toxicity in Wistar rats

The aim of this investigation was to study the effect of cannabis on hematological parameters of Wistar rats induced with copper toxicity. Twenty (20) rats were randomly divided into four groups of five rats each. Group A (negative control) received water only for 15 days, Group B received copper at 200 mg/kg for five days, Group C received copper at 200 mg/kg for five days then treated with cannabis at 300mg/kg for ten days and Group D received cannabis at 300mg/kg only for ten days. All the rats were sacrificed on day sixteen and blood was collected through cardiac puncture and analyzed. Prepared slides from the heart were dehydrated using a dry air oven in xylene for 30 minutes and later mounted on the microscope and viewed using oil immersion ×1000 magnification. In a group induced with copper, we observed a decrease in PVC, RBC, and WBC. Leucopenia, lymphopenia, monocytopenia, and eosinopenia were also observed. However, there was an increase in MCHC, MCH, and MCV. The result of this study shows that copper caused changes in hematological parameters that lead to anemia, also treatment with cannabis caused a relative increase in hematological parameters which was not significant enough to reverse the effect. However, cannabis only was able to cause polycythemia.

Ameliorating Effect of Terminalia arjuna Against 5-Fluorouacil Induced Cardiotoxicity in Wistar Rats

Ameliorating Effect of Terminalia arjuna Against 5-Fluorouacil Induced Cardiotoxicity in Wistar Rats

Cinnamomum zeylanicum Blume (Ceylon cinnamon) bark extract attenuates doxorubicin induced cardiotoxicity in Wistar rats

Anti-tumour efficacy of doxorubicin is hindered by the cumulative dose-dependent cardiotoxicity induced by reactive oxygen species during its metabolism. As Cinnamomum zeylanicum has proven antioxidant potential, objective of this study was to investigate the cardioprotective activity of Cinnamomum bark extract against doxorubicin induced cardiotoxicity in Wistar rats. Physicochemical and phytochemical analysis was carried out and dose response effect and the cardioprotective activity of Cinnamomum were determined in vivo. 180 mg/kg dexrazoxane was used as the positive control. Plant extracts were free of heavy metals and toxic phytoconstituents. In vivo study carried out in Wistar rats revealed a significant increase (p < 0.05) in cardiac troponin I, NT-pro brain natriuretic peptide, AST and LDH concentrations in the doxorubicin control group (18 mg/kg) compared to the normal control. Rats pre-treated with the optimum dosage of Cinnmamomum (2.0 g/kg) showed a significant reduction (p < 0.05) in all above parameters compared to the doxorubicin control. A significant reduction was observed in the total antioxidant capacity, reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase activity while the lipid peroxidation and myeloperoxidase activity were significantly increased in the doxorubicin control group compared to the normal control (p < 0.05). Pre-treatment with Cinnamomum bark showed a significant decrease in lipid peroxidation, myeloperoxidase activity and significant increase in rest of the parameters compared to the doxorubicin control (p < 0.05). Histopathological analysis revealed a preserved appearance of the myocardium and lesser degree of cellular changes of necrosis in rats pre-treated with Cinnamomum extract. In conclusion, Cinnamomum bark extract has the potential to significantly reduce doxorubicin induced oxidative stress and inflammation in Wistar rats.

Chia Seed Oil Ameliorates Doxorubicin-Induced Cardiotoxicity in Female Wistar Rats: An Electrocardiographic, Biochemical and Histopathological Approach

Doxorubicin (DOX) is a potent anti-cancer antibiotic that was widely used for treatment of various cancers. It produces free radicals which result in extreme dose-limiting cardiotoxicity. This study investigated the cardioprotective potential of chia seed oil, an active polyphenolic nutraceutical against doxorubicin-induced cardiotoxicity in Wistar rats. Twenty-four female Wistar rats were divided into four groups (n = 6) which consist of normal control, DOX control, test-A and test-B group. Animals were prophylactically treated with two different doses of test drug, i.e. chia seed oil 2.5 ml/kg/day and 5 ml/kg/day in test-A and test-B groups orally for 7 days. Doxorubicin (25 mg/kg; single dose) was administered intraperitoneally to DOX control, Test-A and Test-B animals on the seventh day to induce cardiotoxicity. ECG analysis was done before and after treatment. Besides ECG, CK, CK-MB, LDH, AST, MDA and GSH were analyzed. DOX had significantly altered ECG, CK, CK-MB, LDH, AST, MDA and GSH. Pre-treatment with chia seed oil significantly alleviated DOX-induced ECG changes and also guarded against DOX-induced rise of serum CK, CK-MB and AST levels. Chia seed oil alleviated histopathological alteration in DOX-treated rats. It also significantly inhibited DOX-induced GSH depletion and elevation of MDA. The present study revealed that chia seed oil exerts cardioprotection against doxorubicin-induced cardiotoxicity in female Wistar rats. Our study opens the perspective to clinical studies to precisely consider chia seed oil as a potential chemoprotectant nutraceutical in the combination chemotherapy with doxorubicin to limit its cardiotoxicity.

Attenuation of doxorubicin-induced cardiotoxicity in Wistar rats by aqueous leaf-extracts of Chromolaena odorata and Tridax procumbens

Ethnopharmacological relevanceChromolaena odorata (L) King and Robinson and Tridax procumbens Linn are used in traditional medicine in the treatment of diabetes mellitus and hypertension. Aim of the studyThis study investigated the potential protective role of aqueous leaf-extracts of Chromolaena odorata and Tridax procumbens against cardiotoxicity induced by doxorubicin. Materials and methodsTo this end, their impact on plasma markers of cardiac integrity, cardiac markers of oxidative stress, cardiac lipids and electrolyte profiles, and activities of cardiac ATPases, lactate dehydrogenase and creatine kinase, were monitored in doxorubicin treated rats. Metformin (250 mg/kg body weight, orally) and both extracts (50, 75 and 100 mg/kg, orally) were daily administered for 14 days; while cardiotoxicity was induced with doxorubicin (15 mg/kg, intra-peritioneally, once on the 12th day of study). ResultsThe plasma activities of creatine kinase, lactate dehydrogenase and AST of Test control were significantly (p < 0.05) higher than those of the other groups. Also, the cardiac malondialdehyde, calcium, chloride, sodium, cholesterol and triglyceride concentrations of Test control were significantly (p < 0.05) higher than those of the others. However, the cardiac concentrations of ascorbic acid, reduced glutathione, magnesium and potassium, and cardiac activities of catalase, glutathione peroxidase, superoxide dismutase, Ca2+-ATPase, Mg2+-ATPase, Na+,K+-ATPase, creatine kinase and lactate dehydrogenase of Test control were significantly (p < 0.05) lower than those of the others. ConclusionsPre-treatment with the extracts and metformin elicited a cardioprotective effect, as indicated by the prevention of doxorubicin-induced cardiac oxidative stress and prevention of adverse alterations in plasma cardiac markers, cardiac lipids and electrolyte profiles, as well as improvement of the activities of cardiac ATPases, creatine kinase and lactate dehydrogenase.