Cardio - and neuroprotective effects of alpha cyclodextrin / moringin complex in sprague dawley rats with isoproterenol- induced myocardial infarction
Myocardial infarction (MI) is a severe form of coronary artery disease resulting from ischemic pathological changes of the myocardium. MI presents with signs of heart and brain affectation, but these are treated independently with different drugs. There is need for alternative treatment options t...
Saved in:
| Main Author: | |
|---|---|
| Format: | Thesis |
| Language: | English |
| Published: |
2023
|
| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/113059/1/113059.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Myocardial infarction (MI) is a severe form of coronary artery disease resulting
from ischemic pathological changes of the myocardium. MI presents with signs
of heart and brain affectation, but these are treated independently with different
drugs. There is need for alternative treatment options that can target both
cardiovascular and behavioral alterations due to MI. Isothiocyanates (ITCs) are
bioactive compounds resulting from myrosinase catalyzed hydrolysis of
glucosinolates (GLs). ITCs are derived from plants and have been shown to
protect the heart and brain from oxidative stress in various cardiovascular and
neuronal diseases’ models. In previous studies, ITCs normalized hemodynamic
variables, behavior as well as heart and brain redox status and morphology.
Moringa oleifera Lam. seeds are rich in glucomoringin (a GL) the precursor of
moringin (an ITC). The cardio- and neuroprotective effects of the ITC moringin
(MG) as well as its novel formulation (alpha-cyclodextrin/moringin complex (α-
CD/MG)) have not been studied on MI. M. oleifera was chosen because of its
powerful antioxidant and cardioprotective effects and is believed to provide
benefits in MI. This study was designed to investigate the potential of MG and
α-CD/MG in protecting the heart and brain against MI-induced oxidative stress
in isoproterenol-induced MI rat model. MG obtained from myrosinase catalyzed
bioactivation of glucomoringin (GMG) isolated from M. oleifera seeds, was
characterized with high performance liquid chromatography (HPLC) and
nuclear magnetic resonance spectroscopy (NMR). Similarly, newly formulated
α-CD/MG was characterized using one- and two-dimensional NMR. HPLC
revealed successful bioactivation of GMG to MG after 15 min of incubation at
37 ℃ while NMR confirmed the molecular structures of MG and α-CD/MG. Male
Sprague Dawley rats were grouped into 4 groups of eight. MG and α-CD/MG
groups were respectively pretreated via oral gavage with MG and α-CD/MG at
20mg/kg and 42 mg/kg body weight diluted in 2 ml phosphate buffered solution
(PBS) for seven days. While control and MI groups received only PBS. In the
last two days of pretreatment, MI was induced by the subcutaneous
administration of isoproterenol hydrochloride (85 mg/kg body weight) in 2 ml of
normal saline 24 hr apart. Induction of MI in rats was successful as confirmed
with serum diagnostic cardiac markers. Data were analyzed and presented as
mean ± standard error of means. The difference between means was
determined using one-way analysis of variance (ANOVA), and the level of
significance was reported at p≤0.05. Pretreatment of rats with MG and α-CD/MG
significantly modified hemodynamic alterations, behavior, heart and brain
oxidative stress and architectural distortions compared to vehicle-pretreated MI
rats. Non-invasive CODA readings showed significant modification in
tachycardia (heart rate of 345±15 vs 466±4) and hypotension (systolic blood
pressure 115±3 vs 77±2) while Open Field Test (OFT) parameters revealed
reduced anxiety-like behaviors (number of lines crossed 29 vs 8) in α-CD/MG
compared to vehicle-pretreated MI rats. Significant difference in serum cardiac
troponin I (270±1.46 vs 407±0.52) and creatine kinase-MB (93±2.16 vs 155
±7.58), hippocampal dopamine (2.35±0.27 vs 0.88±0.04) and serotonin (0.4
±0.02 vs 0.25±0.02) levels, oxidative stress markers as well as microscopic
abnormalities were favorably modified with α-CD/MG pretreatment compared to
vehicle-pretreated MI rats. Conclusively, and for the first time MG and α-CD/MG
exhibited significant suppression of myocardial and brain oxidative stress
evidenced by alleviation of behavioral, hemodynamic, biochemical, and
histological alterations from isoproterenol-induced MI. Hence, α-CD/MG appears
to be a novel alternative in the prevention of cardiovascular and behavioral
manifestations of MI. Nonetheless, there is need for further studies to gain more
insight into the mechanism of action of α-CD/MG in MI. |
|---|