scholarly journals Irvingia gabonensis Seed Extract: An Effective Attenuator of Doxorubicin-Mediated Cardiotoxicity in Wistar Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Olufunke Olorundare ◽  
Adejuwon Adeneye ◽  
Akinyele Akinsola ◽  
Phillip Kolo ◽  
Olalekan Agede ◽  
...  

Cardiotoxicity as an off-target effect of doxorubicin therapy is a major limiting factor for its clinical use as a choice cytotoxic agent. Seeds of Irvingia gabonensis have been reported to possess both nutritional and medicinal values which include antidiabetic, weight losing, antihyperlipidemic, and antioxidative effects. Protective effects of Irvingia gabonensis ethanol seed extract (IGESE) was investigated in doxorubicin (DOX)-mediated cardiotoxicity induced with single intraperitoneal injection of 15 mg/kg of DOX following the oral pretreatments of Wistar rats with 100-400 mg/kg/day of IGESE for 10 days, using serum cardiac enzyme markers (cardiac troponin I (cTI) and lactate dehydrogenase (LDH)), cardiac tissue oxidative stress markers (catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH)), and cardiac histopathology endpoints. In addition, both qualitative and quantitative analyses to determine IGESE’s secondary metabolites profile and its in vitro antioxidant activities were also conducted. Results revealed that serum cTnI and LDH were significantly elevated by the DOX treatment. Similarly, activities of tissue SOD, CAT, GST, and GSH levels were profoundly reduced, while GPx activity and MDA levels were profoundly increased by DOX treatment. These biochemical changes were associated with microthrombi formation in the DOX-treated cardiac tissues on histological examination. However, oral pretreatments with 100-400 mg/kg/day of IGESE dissolved in 5% DMSO in distilled water significantly attenuated increases in the serum cTnI and LDH, prevented significant alterations in the serum lipid profile and the tissue activities and levels of oxidative stress markers while improving cardiovascular disease risk indices and DOX-induced histopathological lesions. The in vitro antioxidant studies showed IGESE to have good antioxidant profile and contained 56 major secondary metabolites prominent among which are γ-sitosterol, Phytol, neophytadiene, stigmasterol, vitamin E, hexadecanoic acid and its ethyl ester, Phytyl palmitate, campesterol, lupeol, and squalene. Overall, both the in vitro and in vivo findings indicate that IGESE may be a promising prophylactic cardioprotective agent against DOX-induced cardiotoxicity, at least in part mediated via IGESE’s antioxidant and free radical scavenging and antithrombotic mechanisms.

Author(s):  
Bryan Gardiner ◽  
Julie A. Dougherty ◽  
Devasena Ponnalagu ◽  
Harpreet Singh ◽  
Mark Angelos ◽  
...  

2014 ◽  
Vol 66 (3) ◽  
pp. 1075-1081
Author(s):  
Ivan Simic ◽  
Violeta Iric-Cupic ◽  
Rada Vucic ◽  
Marina Petrovic ◽  
Violeta Mladenovic ◽  
...  

The aim of the present study was to evaluate the subchronic effects of 3,4-methylenedioxymethamphetamine on several oxidative stress markers: index of lipid peroxidation (ILP), superoxide dismutase (SOD) activity, superoxide radical (O2.-) levels, and reduced glutathione (GSH) levels in the frontal cortex, striatum and hippocampus of the rat. The study included 64 male Wistar rats (200-250g). The animals were treated per os with of 5, 10, or 20 mg/kg of 3,4-methylenedioxymethamphetamine (MDMA) every day for 15 days. The subchronic administration of MDMA resulted in an increase in ILP, SOD and O2.-, and a decrease in GSH, from which we conclude that oxidative stress was induced in rat brain.


2020 ◽  
Vol 40 (6) ◽  
pp. 737-747
Author(s):  
Agnieszka Ścibior ◽  
Konrad A. Szychowski ◽  
Iwona Zwolak ◽  
Klaudia Dachowska ◽  
Jan Gmiński

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Olufunke Olorundare ◽  
Adejuwon Adeneye ◽  
Akinyele Akinsola ◽  
Sunday Soyemi ◽  
Alban Mgbehoma ◽  
...  

Trastuzumab (TZM) is a humanized monoclonal antibody that has been approved for the clinical management of HER2-positive metastatic breast and gastric cancers but its use is limited by its cumulative dose and off-target cardiotoxicity. Unfortunately, till date, there is no approved antidote to this off-target toxicity. Therefore, an acute study was designed at investigating the protective potential and mechanism(s) of CVE and IGE in TZM-induced cardiotoxicity utilizing cardiac enzyme and oxidative stress markers and histopathological endpoints. 400 mg/kg/day CVE and IGE dissolved in 5% DMSO in sterile water were investigated in Wistar rats injected with 2.25 mg/kg/day/i.p. route of TZM for 7 days, using serum cTnI and LDH, complete lipid profile, cardiac tissue oxidative stress markers assays, and histopathological examination of TZM-intoxicated heart tissue. Results showed that 400 mg/kg/day CVE and IGE profoundly attenuated increases in the serum cTnI and LDH levels but caused no significant alterations in the serum lipids and weight gain pattern in the treated rats. CVE and IGE profoundly attenuated alterations in the cardiac tissue oxidative stress markers’ activities while improving TZM-associated cardiac histological lesions. These results suggest that CVE and IGE could be mediating its cardioprotection via antioxidant, free radical scavenging, and antithrombotic mechanisms, thus, highlighting the therapeutic potentials of CVE and IGE in the management of TZM-mediated cardiotoxicity.


2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Olufunke Esan Olorundare ◽  
Adejuwon Adewale Adeneye ◽  
Akinyele Olubiyi Akinsola ◽  
Daniel Ayodele Sanni ◽  
Mamoru Koketsu ◽  
...  

Doxorubicin is widely applied in hematological and solid tumor treatment but limited by its off-target cardiotoxicity. Thus, cardioprotective potential and mechanism(s) of CVE in DOX-induced cardiotoxicity were investigated using cardiac and oxidative stress markers and histopathological endpoints. 50–400 mg/kg/day CVE in 5% DMSO in distilled water were investigated in Wistar rats intraperitoneally injected with 2.5 mg/kg DOX on alternate days for 14 days, using serum troponin I and LDH, complete lipid profile, cardiac tissue oxidative stress marker assays, and histopathological examination of DOX-treated cardiac tissue. Preliminary qualitative and quantitative assays of CVE’s secondary metabolites were also conducted. Phytochemical analyses revealed the presence of flavonoids (34.79 ± 0.37 mg/100 mg dry extract), alkaloids (36.73 ± 0.27 mg/100 mg dry extract), reducing sugars (07.78 ± 0.09 mg/100 mg dry extract), and cardiac glycosides (24.55 ± 0.12 mg/100 mg dry extract). 50–400 mg/kg/day CVE significantly attenuated increases in the serum LDH and troponin I levels. Similarly, the CVE dose unrelatedly decreased serum TG and VLDL-c levels without significant alterations in the serum TC, HDL-c, and LDL-c levels. Also, CVE profoundly attenuated alterations in the cardiac tissue oxidative stress markers’ activities while improving DOX-associated cardiac histological lesions that were possibly mediated via free radical scavenging and/or antioxidant mechanisms. Overall, CVE may play a significant therapeutic role in the management of DOX-induced cardiotoxicity in humans.


2010 ◽  
Vol 36 (1) ◽  
pp. 4-9 ◽  
Author(s):  
Palanisamy Pasupathi ◽  
Uma Manivannan ◽  
Perisamy Manivannan ◽  
Mathiyalagan Deepa

Free radicals play an important role in the pathogenesis of tissue damage in many clinical disorders, including atherosclerosis. This study was to investigate lipids and oxidative stress markers among women with 50 healthy non-pregnant compare with 50 healthy pregnant and 50 pregnancy-induced hypertensive subjects and correlate with cardiac troponin I (cTnI) and troponin T (cTnT). The level of plasma thiobarbituric acid reactive substances (TBARS), cTnI and cTnT levels significantly increase in pregnancy-induced hypertension compare with other groups. The level of lipids significantly altered in pregnancy-induced hypertension. Conversely, the activities of both enzymatic and non-enzymatic antioxidants were significantly decreased in pregnancy-induced hypertension compared to non-pregnant and healthy pregnant. Our data suggest that there is an imbalance between lipoperoxidation and antioxidants levels during pregnancy and preeclampsia. Serum cTnI and cTnT are elevated in women with pregnancy-induced hypertension indicating some degree of cardiac myofibrillar damage and cardiac dysfunction.Online: 11 July 2010DOI: http://dx.doi.org/10.3329/bmrcb.v36i1.4806Bangladesh Med Res Counc Bull 2010; 36: 4-9


2019 ◽  
Vol 493 ◽  
pp. S628
Author(s):  
V. Castañón Bernardo ◽  
C. Barneo Caragol ◽  
S. Rodríguez González ◽  
I. Vega Naredo ◽  
L. Sánchez Castro ◽  
...  

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