Faculty of Basic Medical Sciences

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African Vegetables (Clerodendrum volibile Leaf and Irvingia gabonensis Seed Extracts) Effectively Mitigate Trastuzumab Induced Cardiotoxicity in Wistar Rats
(Oxidative Medicine and Cellular Longevity, 2020-10-15) Akinsola Akinyele O
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. 400mg/kg/day CVE and IGE dissolved in 5% DMSO in sterile water were investigated in Wistar rats injected with 2.25mg/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 400mg/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.
Ameliorative Potential of Clerodendrum volubile Ethanol Leaf Extract on Doxorubicin-Induced Hepatorenal Toxicities in Rats
(Pharmacology and Toxicology of Natural Medicines, 2021-07-09) Akinsola Akinyele O
Background and Purpose: Hepatorenal toxicity is a side effect of the anthracycline cytotoxic antibiotics, doxorubicin that is used in cancer treatment. The study investigated the ameliorative potential of Clerodendrum volubile ethanol leaf extract (CVE) on doxorubicin (DOX)-induced hepatorenal toxicities. Methods: Male Wistar rats were pretreated with Clerodendrum volubile ethanol leaf extract (50 - 400 mg/kg/day, p.o) followed by intraperitoneal injection of 2.5 mg/kg of DOX on alternate days for 14 days. Hepatorenal toxicity was assessed using renal function parameters (serum electrolytes, blood urea and creatinine), hepatic function endpoints [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), total protein (TP), albumin (ALB) and total bilirubin (TB)]. In addition, the antioxidant activity in the kidney and liver tissues were assayed and histological studies of these tissues were also conducted. Results: Oral pretreatment with 50 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day and 400 mg/kg/day of CVE remarkably ameliorated DOX-induced liver and kidney injury by lowering the serum ALT, AST, ALP, Cr and BUN levels. CVE pretreatment remarkably ameliorated DOX-induced increases in the CAT, SOD and GPx activities and MDA levels compared to the DOX-treated rats. The biochemical changes were corroborated by improvements in the DOX-induced histological lesions seen in the hepatic and renal tissues examined. Conclusions: Overall, these findings suggest that Clerodendrum volubile ethanol leaf extract elicits protective effect against DOX-induced hepatorenal toxicities mediated primarily via oxidative stress suppression and improvement in the free radicals scavenging activities of CVE.
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
(Toxicology Reports, 2024-01-15) Akinsola Akinyele O
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
Assessment of Hygiene Practices among Eateries in Amai Community: A Mixed Intervention Study
(International Journal of Caring Sciences, 2023) Akinsola Akinyele O
Background: There is an observable increase in food-borne diseases, food poisoning among the rural dwellers in the study setting which is perceived to be due to consumption of poorly handled food. This was a strong justification for this study. Objective: This study aimed at assessing the environmental and storage system for unprocessed and processed food amongst identified eateries and to implement interventions based on observed wrong practices. Methodology: This study adopted a mixed descriptive cross-sectional intervention study (a questionnaire, observational check list and Key Informant Interviews for data collection among 38 respondents). The items in the checklist were adapted from World Health Organization standard for assessing food vendors and premises. The quantitative data collected was coded and analyzed using SPSS version 20 while qualitative data was transcribed verbatim with themes and sub-themes. Results: At pre-intervention phase, apron use was 15 (39.5%) with 3 (7.9%) consistency; chef caps usage was 14 (36.8%) with 8 (21.1%) consistency but there was no observable use of facemasks. Twenty-three (60.0%) reported Personal Protective Equipment (PPE) burden. At the post-intervention phase, apron use was 37 (97.4%) with 35 (92.1%) consistency; chef cap use was 28 (73.7%) with 26 (68.4%) consistency; facemask use was 33 (86.8%) with 19 (50.0%) consistency. By implication, 36.8% wear it under the chin, and 13.2% still feel uncomfortable using it. Conclusion: Interventions can influence the practice of good food handling practice among food handlers and consistency in the use of PPE to prevent food contamination via droplets.
Clerodendrum volubile Ethanol Leaf Extract: A Potential Antidote to Doxorubicin-Induced Cardiotoxicity in Rats
(Journal of Toxicology, 2020-07-04) Akinsola Akinyele O
Doxorubicin is widely applied in hematological and solid tumor treatment but limited by its off-target cardiotoxicity. us, cardioprotective potential and mechanism(s) of CVE in DOX-induced cardiotoxicity were investigated using cardiac and ox idative stress markers and histopathological endpoints. 50–400mg/kg/day CVE in 5% DMSO in distilled water were investigated in Wistar rats intraperitoneally injected with 2.5mg/kg DOX on alternate days for 14days, 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±0.37mg/100mg dry extract), alkaloids (36.73±0.27mg/100mg dry extract), reducing sugars (07.78±0.09mg/100mg dryextract), and cardiac glycosides (24.55±0.12mg/100mg dry extract). 50–400mg/kg/ day CVEsignificantly 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 histo logical 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.
EFFECTS OF WHOLE CANNABIS SATIVA INGESTION ON BEHAVIOURAL PATTERNS AND OXIDATIVE STRESS IN MICE BRAIN TISSUES
(Animal Research International, 2019-04-11) Akinsola Akinyele O
The 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.
EXPERIMENTAL 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 O
Objective: 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.
GC/MS Analysis and a 30-day Toxicological Evaluation of a Nigerian Immunomodulatory Polyherbal Supplement (PHS)
(Pharmacology and Toxicology of Natural Medicines, 2023-11-09) Akinsola Akinyele O
Background and Purpose: A Nigerian-formulated polyherbal supplement (PHS) is consumed for its folkloric claims of boosting the immune system. The aim of this study was to toxicologically evaluate a 30-day administration of PHS. Methods: Gas Chromatography/Mass Spectrometry (GC/MS) analysis was carried out on the ethanol extract of PHS. Thirty-two Wistar rats were randomly assigned to four groups. One group served as control while the other three groups were administered 250, 500, and 1000 mg/kg/day of PHS for 30 consecutive days. The animals were anesthetized, and cardiac puncture was used to obtain whole blood for hematology and serum biochemistry. In vivo, antioxidant assays were also carried out on the liver homogenates. The liver, kidneys, and heart were examined histologically. Results: The most abundant compounds identified were eucalyptol, alpha-pinene, and phytol. There were no adverse hematological effects. Total cholesterol, LDL-C, and catalase were reduced significantly (P<0.05). At 1000 mg/kg/day, there was a significant increase in creatinine, sodium ion, and glutathione peroxidase concentration. The histological examination of the heart, kidneys, and liver revealed that PHS did not cause any major tissue lesions at 250 and 500 mg/kg/day. Tissue lesions and pathologies were obvious at 1000 mg/kg/day. Conclusion: The polyherbal supplement seems to be relatively safe if used at doses up to 250 mg/kg/day. Higher doses may cause renal and hepatic lesions.
Hypolipidaemic Effect of Lycopene from Red Tomatoes (Solanum lycopersicum L.) and its Potential for the Prevention of Cardiovascular Diseases
(Tropical Journal of Natural Product Research, 2024-02-01) Akinsola Akinyele O
The Nutritional and therapeutic benefits of lycopene from red tomatoes and its products cannot be overemphasized. Therefore, this study aimed to evaluate the hypolipidaemic effect of lycopene in three different preparations of red tomatoes in hyperlipidemic rats. Forty male Wistar rats were used for the study. The rats were divided into four groups (A - D) of 10 animals each. Group A was used as the control and received basal home diet throughout the duration of the experiment. Groups B, C, and D were fed with hyperlipidemic diets for one month, followed by lycopene in three different preparations of red tomatoes (Raw tomatoes, Tomato juice, and Cooked tomatoes) for another one month. Body weight and growth rate of the rats were monitored. The serum lipid profiles of the rats after administration of the hyperlipidaemic diet as well as after treatment with red tomato preparations were determined following standard procedures. Results showed that lycopene reduced weight gain induced by hyperlipidaemic diet, increased faecal fat content, and significantly reduced hyperlipidaemia in rats. The cooked tomatoes had the greatest effect in lowering serum total cholesterol, low density lipoprotein, and increasing high density lipoprotein levels. This suggests that lycopene present in cooked tomatoes are more readily absorbed in the intestine and therefore achieve higher concentration in the blood. Based on the findings from this study, dietary red tomatoes rich in lycopene may play a significant role in weight reduction, and in lowering plasma cholesterol which directly or indirectly reduces the risk of cardiovascular diseases.
Irvingia gabonensis Seed Extract: An Effective Attenuator of Doxorubicin-Mediated Cardiotoxicity in Wistar Rats
(Oxidative Medicine and Cellular Longevity, 2020-10-23) Akinsola Akinyele O
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 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.
Ocimum Gratissimum Linn. Leaf Extract and Fractions Pre-Treatments are not Associated With Deleterious Electrocardiogram Changes in Trastuzumab Intoxicated Wistar Rats
(Al-Nahrain Journal of Science, 2024-06-15) Akinsola Akinyele O
Trastuzumab (TZM) treatment is known to be associated with arrhythmogenic potential which primarily is the basis for its cardiotoxicity. The purpose of this study was to investigate the acute influence of oral pretreatments with 100 mg/kg/day of Ocimun gratissimum ethanolic leaf extract (OG) and its fractions (petroleum ether, PEOG; ethyl acetate, EAOG; and ethanolic extract, EOG) as well as valsartan-lisinopril fixed dose combination (VAL-LSP) on electrocardiogram (ECG) of Wistar rats intaperitoneally treated with 2.25 mg/kg/day TZM for 7 days. Young adult male Wistar rats were randomly allotted into 12 groups of 6 rats per group. The rats were subjected to electrocardiograms (ECG) measurement using non-invasive procedures on days 1 and 7 of the experiment. Results showed that oral pretreatment with OG and its fractions (except EOG) as well as VAL-LSP fixed dose combination did not cause any remarkable changes in the ECG patterns of TZM-treated rats indicating that their relative oral safety in TZM chemotherapy. On the other hand, EOG pretreatment caused significant shortening of the OT/QTc interval in the TZM-treated rats highlighting the arrhthymogenic potential of this fraction. Overall, the study highlighted the arrhythmogenic potential of EOG in TZM chemotherapy while OG and its other solvent fractions as well as VAL-LSP could be considered relatively safe for use as adjuvants in TZM chemotherapy.
Preclinical investigation on the antinociceptive, antipyretic, antiinflammatory and antioxidant activities of Ananas comosus leaf extract
(Journal of Basic and Applied Pharmacology, 2025-03-01) Akinsola Akinyele O
Ananas comosus is a well-known medicinal plant used in traditional medicine for various therapeutic purposes, including the treatment of pain, fever and inflammation. This study aimed to evaluate the antinociceptive, anti-inflammatory, antipyretic and antioxidant activities of the ethanolic leaf extract of A. comosus and the mechanism by which it produces its antinociceptive effects in mice. The antinociceptive activity of ethanolic leaf extract of A. comosus was evaluated using an acetic acid-induced writhing test and a formalin-induced pain test. The mechanism of anti nociception was determined by pretreating mice with various antagonists (naloxone, glibenclamide, atropine, nifedipine and theophyline) before administration of the extract (800 mg/kg) during the acetic acid-induced writhing test. The antipyretic effect was evaluated using yeast-induced pyrexia in mice, while formalin-induced inflammation was used to evaluate the anti inflammatory effects. The extract demonstrated potent antinociceptive activity compared to the control group in the acetic acid-induced writhing test and in the formalin-induced pain models. Naloxone, glibenclamide, atropine and nifedipine did not block the antinociceptive activity. However, theophylline significantly reversed the antinociceptive effect in the acetic acid-induced writhing test. The extract also showed antipyretic and anti-inflammatory effects, while the results of the antioxidant study showed that it has high antioxidant properties. The study results showed that the extract has potent antinociceptive, antipyretic, anti-inflammatory and antioxidant effects.
Selected Antihypertensive Agents and their Fixed-Dose Combinations Effectively Ameliorate Trastuzumab-Mediated Cardiac Dysfunctions in Rats
(Nigerian Journal of Physiological Sciences, 2021-06) Akinsola Akinyele O
This 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.
Theaflavin Alleviates Memory Deficit and Anxiety-Like Phenotypes in Valproic Acid Murine Model of Autism: Impact on Cholinergic and Oxido-Nitrigic Stress Mechanisms
(Tropical Journal of Natural Product Research, 2025-01-01) Akinsola Akinyele O
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition marked by deficits in communication and repetitive behaviors. Its etiology is multifactorial, involving genetic, epigenetic, and environmental factors, complicating diagnosis and treatment. This study explores the neuroprotective effects of theaflavin (TF) in a valproic acid (VPA)-induced murine model of autism, focusing on its impact on anxiety, memory, oxidative-nitric stress, and cholinergic pathways. Pregnant Swiss albino mice were injected with VPA (250 mg/kg) on gestational day 13. Male offspring, confirmed to exhibit autistic-like behaviors through tests such as Y-maze, NORT, EPM, LDT, and HBT, were treated with TF (10 or 20 mg/kg) or 1% DMSO (10 mL/kg) for 30 days. Behavioral assessments were repeated post-treatment, and brain samples were analyzed for oxidative stress markers (NO, GSH) and histological damage in the medial prefrontal cortex and hippocampus. VPA-exposed mice showed impaired memory, increased AChE and NO levels, reduced GSH, and neuronal damage. TF significantly improved memory in the Y-maze [F(3, 16) = 9.448; (p = 0.0008)] and NORT [F(3, 16) = 15.12; (p < 0.0001)] but did not significantly affect anxiety-like behaviors in EPM, LDT, or HBT. TF treatment reduced oxidative stress, mitigated neuronal damage, and enhanced cholinergic activity, highlighting its potential as a therapeutic agent for autism.
Therapeutic Potentials of Selected Antihypertensive Agents and Their Fixed-Dose Combinations Against Trastuzumab-Mediated Cardiotoxicity
(Frontiers in Pharmacology, 2021-03-04) Akinsola Akinyele O
Trastuzumab (TZM) is useful in the clinical management of HER2-positive metastatic breast, gastric, and colorectal carcinoma but has been limited by its off-target cardiotoxicity. This study investigates the therapeutic potentials of 0.25 mg/kg/day amlodipine, 0.035mg/kg/day lisinopril, 5 mg/kg/day valsartan, and their fixed-dose combinations in TZM-intoxicated Wistar rats that were randomly allotted into 10 groups of 6 rats for each group. Group I rats were treated with 10 ml/kg/day sterile water orally and 1 ml/kg/day sterile water intraperitoneally; Groups II, III, and IV rats were orally gavaged with 5 mg/kg/day valsartan and 1 ml/kg/day sterile water intraperitoneally, 0.25 mg/kg/day amlodipine and 1 ml/kg/day sterile water via the intraperitoneal route, 0.035 mg/kg/day lisinopril and 1 ml/kg/day sterile water administered intraperitoneally, respectively. Group V rats were orally treated with 10 ml/kg/day of sterile water prior to intraperitoneal administration of 2.25 mg/kg/day of TZM. Groups VI–VIII rats were equally pretreated with 5 mg/kg/day valsartan, 0.25 mg/kg/day amlodipine, and 0.035 mg/kg/day lisinopril before intraperitoneal 2.25 mg/kg/day TZM treatment, respectively; Groups IX and X rats were orally pretreated with the fixed-dose combinations of 0.25mg/kg/day amlodipine +0.035mg/kg/day lisinopril and 5mg/kg/day valsartan +0.035mg/kg/day lisinopril, respectively, before TZM treatment. Cardiac injury and tissue oxidative stress markers, complete lipids profile, histopathological, and immunohistochemical assays were the evaluating endpoints. Results showed that repeated TZMtreatments caused profound increases in the serum TG and VLDL-c levels, serum cTnI and LDH levels, and cardiac tissue caspase-3 and-9 levels but decreased BCL-2 expression. TZM also profoundly attenuated CAT, SOD, GST and GPx activities, and increased MDA levels in the treated tissues. In addition, TZM cardiotoxicity was characterized by marked vascular and cardiomyocyte congestion and coronary artery microthrombi formation. However, the altered biochemical, histopathological, and immunohistochemical changes were reversed with amlodipine, lisinopril, valsartan, and fixed-dose combinations, although fixed-dose valsartan/lisinopril combination was further associated with hyperlipidemia and increased AI and CRI values and coronary artery cartilaginous metaplasia. Thus, the promising therapeutic potentials of amlodipine, lisinopril, valsartan and their fixed-dose combinations in the managementofTZMcardiotoxicity, majorly mediated via antiapoptotic and oxidative stress inhibition mechanisms were unveiled through this study
TOXICITY AND ANTIOXIDANT ASSESSMENT OF ETHANOL LEAF EXTRACT OF HIBISCUS SURATTENSIS IN WISTAR RATS: HEPATOTOXICITY EVALUATION
(African Journal of Pharmaceutical Research and Development, 2024-12-20) Akinsola Akinyele O
Hibiscus surattensis is a medicinal plant with a vast beneficial use in the management and cure of a variety of diseases, ranging from urethritis to inflammation and vertigo among others. Notwithstanding the population's increasing use of it, particularly in rural regions, there is still lack of adequate investigation into its toxicity profile. The aim of this study was to investigate the ethanolic extract of Hibiscus surattensis leaf's potential for hepatotoxicity in Wistar rats. The acute toxicity test was carried out in two phases (phases 1 and 2). Phase 1, used nine mice which were randomized into three groups (n=3), receiving graded doses of the extract as follows: 10, 100, and 1000 mg/kg, ip respectively. Phase 2 used three mice which were randomized into three groups of one mouse each and administered the extract in graded doses of 2000, 3500, and 5000 mg/kg, ip, respectively. They were monitored for behavioral abnormalities, toxicity signs, and mortality for 24 hours following treatment. A subacute toxicity experiment was then carried out, in which Wistar rats were given oral doses of H. surattensis extract (141, 282, and 424 mg/kg) every day for eight (8) days. Behavioural changes, haematological and liver function parameters, in-vivo oxidative stress markers and histological changes were then evaluated. The LD50 of H. surattensis leaf extract was estimated to be 1414 mg/kg. Results revealed significant rise (p<0.01-0.001) in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), conjugated bilirubin (C.B) and total bilirubin (T.B), as well as in white blood cell (WBC) and platelet at high doses of the extract-treated rats compared to control. A significant reduction was recorded in catalase among other antioxidant parameters while the histopathological evaluations showed mild alterations. While caution is urged during long-term administration, administration of H. surattensis ethanolic extract may be safe at the dosages studied in this investigation. .
VASORELAXANT 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 O
Objectives: 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

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