Department of Physiology
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- ItemVASORELAXANT MECHANISM(S) OF CLERODENDRUM VOLUBILE ETHANOL LEAF EXTRACT IN NORMAL AND DOXORUBICIN-TREATED ENDOTHELIUM INTACT AORTIC RINGS(Asian Journal of Pharmaceutical and Clinical Research, 2022-05-20) Akinsola Akinyele OObjectives: Doxorubicin (DOX) is a highly effective antibiotics anthracycline cytotoxic agent with a broad spectrum of activity in the treatment of solid and hematological malignancies. However, DOX is notorious for inducing cardiotoxicity and vascular dysfunction as its common off-target side effects. This study evaluated the possible vasorelaxant activity and mechanism(s) of action of Clerodendrum volubile ethanol leaf extract (CVE) in normal and DOX-pretreated endothelium intact aortic rings in Physiological Salt Solution (PSS) in vitro. Methods: The responses were recorded isometrically by an organ bath connected to Data Capsule Acquisition System. Effects of CVE on phenylephrine precontracted endothelium intact rat aortic rings and the influence of the respective blockers for adrenergic, cholinergic, calcium channel, and prostacyclin receptors were investigated to unveil the possible underlying vasorelaxant mechanism(s) of CVE. Results: Our findings showed that CVE significantly induced vasorelaxation in phenylephrine hydrochloride (PE) and KCl precontracted endothelium intact aortic rings in a concentration-dependent manner. Furthermore, the CVE-induced vasorelaxation in PE- and KCl-precontracted aortic rings were inhibited by pre-incubation with atropine and indomethacin indicating that the vasorelaxant effect of CVE was profoundly mediated through cholinergic and prostacyclin mechanisms. Conclusion: Overall, results of this study report for the first time the vasorelaxant effect of CVE in isolated endothelium-intact doxorubicin-treated aortic rings of normotensive rats which was probably cholinergic and prostacyclin-mediated. Thus, results of this study provide further insight into the cardioprotective m
- ItemIrvingia gabonensis Seed Extract: An Effective Attenuator of Doxorubicin-Mediated Cardiotoxicity in Wistar Rats(Oxidative Medicine and Cellular Longevity, 2020-10-23) Akinsola Akinyele OCardiotoxicity 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 15mg/kg of DOX following the oral pretreatments of Wistar rats with 100-400mg/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 100-400mg/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.
- ItemSelected Antihypertensive Agents and their Fixed-Dose Combinations Effectively Ameliorate Trastuzumab-Mediated Cardiac Dysfunctions in Rats(Nigerian Journal of Physiological Sciences, 2021-06) Akinsola Akinyele OThis study evaluates the therapeutic potentials of selected antihypertensive drugs [valsartan (VAL), amlodipine (ADP), lisinopril (LSP) and their fixed-dose combinations [(amlodipine + lisinopril) (ADP + LSP) and (valsartan + lisinopril) (VAL + LSP)] in ameliorating trastuzumab (TZM)‑induced cardiovascular dysfunctions in experimental rats. In-bred female Wistar rats were randomly allotted into 10 groups of 6 rats per group. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) as well as electrocardiogram (ECG) of the treated rats were measured using non-invasive procedures on days 1 and 7 of the experiment, following which the treated rats were sacrificed under light inhaled diethyl ether and histopathological evaluation of all treated hearts was done. Results showed that repeated TZM treatment profoundly (p<0.05) raised SBP, DBP and MAP values from 115.0 ± 17.1 mmHg, 85.1 ± 15.1 mmHg and 94.7 ± 15.5 mmHg, respectively on day 1 to 127.7 ± 27.8 mmHg, 87.4 ± 27.3 mmHg and 100.5 ± 26.4 mmHg, respectively, on day 7. Oral pretreatments with VAL, ADP, LSP and their fixed-dose combinations profoundly (p<0.05) attenuated increases in the SBP, DBP and MAP values with the most significant attenuation mediated by the fixed-dose VAL + LSP combination at the SBP, DBP and MAP values of 103.8 ± 20.6 mmHg, 65.5 ± 18.8 mmHg, and 77.9 ± 18.7 mmHg, respectively. TZM treatment also profoundly (p<0.05) prolonged the QT and corrected QT intervals from 85.0 ± 11.5 ms and 161.6 ± 20.3 ms, respectively, on day 1 to 110.2 ± 21.5 ms and 226.5 ± 41.5 ms, respectively, on day 7. However, these QT and corrected QT interval prolongations were effectively and profoundly attenuated by oral pretreatments with VAL, ADP, LSP and their fixed-dose combinations. In addition, TZM cardiotoxicity was characterized by marked vascular and cardiomyocyte congestion and coronary artery microthrombi formation. However, these histopathological changes were reversed with oral pretreatments with ADP, LSP, VAL and fixed-dosed [(ADP + LSP) and (VAL + LSP)] combinations although fixed-dose VAL + LSP was associated with histopathological lesions of coronary arterial wall cartilaginous metaplasia. Overall, this study revealed the promising therapeutic potentials of VAL, ADP, LSP and their fixed-dose combinations as repurposed drugs for the prevention of TZM-mediated cardiac dysfunctions.
- ItemEFFECTS OF WHOLE CANNABIS SATIVA INGESTION ON BEHAVIOURAL PATTERNS AND OXIDATIVE STRESS IN MICE BRAIN TISSUES(Animal Research International, 2019-04-11) Akinsola Akinyele OThe unregulated habitual use of whole Cannabis sativa remains a challenge for the potential medical usefulness of the plant. As a psychoactive substance with different physiological properties, the onset and extent of its effects are often a factor of the mode of consumption. This study evaluated the neuro-behavioural effects of daily oral ingestion of C. sativa and its modulatory changes in oxidative stress parameters in mice brain tissues. Twenty-five male Swiss albino mice were separated into 5 groups of 5 animals each. Cannabis-diet were prepared from whole dried cannabis and standard mice feed. Groups I – IV, were fed with 40, 20, 10 and 1 % cannabis-diet ad libitum for 14 days, while group V animals were fed the standard mice diet ad libitum for 14 days and served as control. Neuro-behavioural activities were assessed by observing animals rearing, grooming, ambulation, head dipping and freezing times. The brain oxidative stress parameters were assayed to determine the effect of cannabis oral consumption on activity in mice brain. The animals fed with cannabis-diet displayed significantly reduced anxiety but statistically insignificant locomotory function, exploratory tendencies and neophilia, in a quantity dependent manner relative to the controls. Cannabis demonstrated both antioxidant and oxidative stress tendencies. Ingestion of whole cannabis plants may not adversely influence neuro-behavioural patterns in animals. A trade-off between oxidative stress induction and brain tissue injury repair mechanisms may have been elicited by different constituents of Cannabis. Thus, oral ingestion of cannabis may not readily cause changes in neuro-behavioural patterns.
- ItemEXPERIMENTAL THERAPEUTIC EVALUATION OF THE AFRICAN VEGETABLES (CLERODENDRUM VOLUBILE LEAF AND IRVINGIA GABONENSIS SEED EXTRACTS) IN TRASTUZUMAB-MEDIATED HEPATO-RENAL DYSFUNCTION IN WISTAR RATS(Asian Journal of Pharmaceutical and Clinical Research, 2020-11-21) Akinsola Akinyele OObjective: The use of trastuzumab (TZM) in the clinical management of human epidermal growth factor receptor 2 positive metastatic breast and gastric cancers, gastro-esophageal adenocarcinoma, and colorectal carcinoma has been limited by its off-target cardiac, hepatic, and renal toxicities which till date have no effective therapies in either their prevention or amelioration. Thus, the present study is designed at investigating the protective and therapeutic potentials of 400 mg/kg/day Clerodendrum volubile ethanol leaf extract (CVE) and Irvingia gabonensis ethanol seed extract (IGE) pretreatments in TZM-intoxicated Wistar rats based on their reported folkloric use in the local management of kidney and liver diseases and the previously reported therapeutic potential of these African vegetables in TZM cardiotoxicity. Methods: Forty-nine male Wistar rats were randomly allotted into seven groups of seven rats per group. Group I rats were treated with 10 ml/kg/day of 5% dimethyl sulfoxide (DMSO) sterile water p.o. and 1 ml/kg/day 5% DMSO sterile water i.p.; Groups II and III rats were orally pretreated with 400 mg/kg/day CVE and IGE, respectively, 3 h before 1 ml/kg/day/i.p. 5% DMSO sterile water; Group IV rats were orally pretreated with 10 ml/kg/day 5% DMSO sterile water 3 h before 2.25 mg/kg/day/i.p. TZM; and Groups V-VII rats were pretreated with 20 mg/kg/day Vit. C, 400 mg/kg/day CVE, and 400 mg/kg/day IGE all dissolved in 5% DMSO sterile water, respectively, 3 h before i.p. injections of 2.25 mg/kg/day TZM, all for 7 days. Liver function parameters, renal function parameters, oxidative stress markers, and histopathological investigations were the study measuring endpoints. Results: Oral pretreatment with 20 mg/kg/day Vit. C, 400 mg/kg/day CVE and IGE significantly ameliorated TZM-mediated hepatic and renal toxicities by effectively lowering the serum alanine transaminase, aspartate transaminase, alkaline phosphatase, creatinine, and urea levels. CVE and IGE pretreatments also significantly reversed TZM-induced decreases in the hepatic and renal tissue catalase, superoxide dismutase, and glutathione S-transferase activities and reduced malondialdehyde levels. CVE and IGE pretreatments also improved TZM-induced hepatic and renal histological lesions. Conclusions: Overall, the chemotherapeutic/chemopreventive potentials of CVE and IGE in TZM-induced hepatorenal dysfunction were either wholly or partly mediated through free-radical scavenging and antioxidant activities.