scholarly journals African Vegetables (Clerodendrum volibile Leaf and Irvingia gabonensis Seed Extracts) Effectively Mitigate Trastuzumab-Induced Cardiotoxicity in Wistar Rats

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.


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 11 (2) ◽  
pp. 88-98
Author(s):  
Babatunde Ogunlade ◽  
◽  
Olasumbo Afolayan ◽  
Sunday Adelakun ◽  
◽  
...  

Lead (Pb) exposure induces oxidative stress causing imbalance in antioxidant enzymes, cognitive impairments and neurodegeneration. This study investigated the neuroprotective and antioxidant properties of sulphoraphane (SFN) on Pb-induced neurotoxicity of adult Wistar rats. Forty animals (150 ± 20 g) were divided into four groups (n=10): Group A received normal saline as placebo; Group B received 50 mg/kg body weight (bw) of Lead only; Group C received a combination of 50 mg/kg bw of Lead and 50 mg/kg bw of SFN; Group D received 50 mg/kg bw of SFN only. All administration was through oral gavages for 28 days; animals underwent behavioural tests (Morris water and Y- mazes); and thereafter sacrificed and brains extracted. Biochemical estimations of antioxidants (superoxide dismutase, reduced glutathione, and catalase), oxidative stress markers (malondialdehyde, nitric oxide, and hydrogen peroxide), neurotransmitters (dopamine, serotonin, and norepinephrine) and hippocampal histology were done. The results showed significant increase in escape latency, norepinephrine and oxidative stress markers with concomitant decrease percentage correct alternation, serotonin, dopamine and antioxidant enzymes in Pb exposed rats compared with the control. However, the co-administration of SFN and Pb significantly attenuated Pb neurotoxicity. Sulphoraphane is capable of ameliorating oxidative stress induced neurobehavioural deficits and hippocampal neurochemistry caused by Pb exposure in Alzheimer’s type animal model of neurodegenerative disorder.


2020 ◽  
Vol 8 (3) ◽  
pp. 225-238
Author(s):  
Mona Navaei-Nigjeh ◽  
Marzieh Daniali ◽  
Mahban Rahimifard ◽  
Mohammad R. Khaksar

Background: Excessive use of diazinon, as an organophosphate pesticide (OP), contributes to cytotoxic and pathologic cellular damage and, in particular, oxidative stress. However, metal-oxide nanoparticles (NPs), such as cerium oxide (CeO2) and yttrium oxide (Y2O3), with the property of free radical scavenging demonstrated beneficial effects in the alleviation of oxidative stress biomarkers. Objective: The aims of this study include evaluating beneficial effects of CeO2 NPs, Y2O3 NPs, and their combination against diazinon-induced oxidative stress in different tissues of brain, heart, lung, kidney, liver, and spleen. Methods: Eight randomized groups of 6 adult male Wistar rats were formed. Each group of rats administered a different combination of diazinon, CeO2 and Y2O3 NPs daily and levels of oxidative stress markers, such as reactive oxygen species (ROS), lipid peroxidation (LPO), total thiol molecules (TTM) and total anti-oxidant power (TAP) and catalase enzyme, were measured after 2 weeks of the treatment. Results: Measurements of the mentioned markers in the brain, heart, lung, kidney, liver, and spleen showed that the administration of NPs could significantly alleviate the oxidative stress induced by diazinon. However, the findings of this study illustrated that the combination of both CeO2 and Y2O3 NPs led to a better reduction in oxidative stress markers. Conclusion: Sub-acute exposure of diazinon in rats led to increased levels of oxidative stress markers in pivotal tissues such as the brain, heart, lung, kidney, liver, and spleen. CeO2 and Y2O3 NPs neutralize the oxidative stress to compensate diazinon-induced tissue damages. Lay Summary: Organophosphate pesticides (OPs), which are mainly used for pest control, are responsible for the entry of pesticides into the human food cycle. Organophosphate such as diazinon increases the molecular biomarkers of oxidative stress inside the cells of vital tissues such as the heart, liver, lungs, etc. Metal oxide nanoparticles (NPs) such as cerium oxide (CeO2) and yitrium oxide (Y2O3) can have free radical scavenging potential under oxidative stress and through various mechanisms. Although these nanoparticles reduce oxidative stress, it should be borne in the design of the study that additional doses of these substances reverse the beneficial effects.


2019 ◽  
Vol 44 (5) ◽  
pp. 521-527 ◽  
Author(s):  
Emran Habibi ◽  
Milad Arab-Nozari ◽  
Pedram Elahi ◽  
Maryam Ghasemi ◽  
Fatemeh Shaki

Ethanol is the most widely abused drug in the world and its long-term use induces oxidative stress in the liver tissue. The aim of this study was to evaluate protective effect of Viola odorata against ethanol-induced hepatotoxicity in Wistar rat. Animals were divided into 9 groups as follows: control (normal saline), ethanol (10 mg/kg, intraperitoneally), ethanol with 3 doses (125, 250, and 500 mg/kg) of ethyl acetate flower and leaf extracts, and positive control (vitamin E 80 mg/kg). Animals were gavaged 30 min before ethanol injection for 28 days. Then, animals were killed and the livers were separated. Oxidative stress parameters, including reactive oxygen species, lipid peroxidation, and protein carbonyl as well as glutathione content, were evaluated. Also, histopathological examination was performed and assessment of blood alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total antioxidant capacity were evaluated. Ethanol significantly increased oxidative stress markers in liver. Interestingly, administration of both extracts significantly decreased oxidative stress markers in liver tissue and biochemical parameters in the plasma. In addition, abnormal pathological features were improved after treatment with flower and leaf extracts. These results suggested that V. odorata can be considered a candidate for improving conditions due to ethanol-induced tissue oxidative damage because of its antioxidant activity.


2010 ◽  
Vol 23 (5) ◽  
pp. 473-480 ◽  
Author(s):  
E. E. Nishi ◽  
E. B. Oliveira-Sales ◽  
C. T. Bergamaschi ◽  
T. G. C. Oliveira ◽  
M. A. Boim ◽  
...  

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.


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