Temitayo Olabisi Ajibade

Sodium fluoride induces hypertension and cardiac complications through generation of reactive oxygen species and activation of nuclear factor kappa beta

Human exposure to sodium fluoride through its daily usage is almost inevitable. Cardiovascular and renal dysfunction has been associated with fluoride toxicity. Therefore, this study investigated the mechanism of action of sodium fluoride (NaF) induced hypertension and cardiovascular complications Forty male albino rats of an average of 10 rats per group were used. Group A received clean tap water. Toxicity was induced in Group B to D by administering graded doses of NaF through drinking water ad libitum for 10 days at 150 ppm, 300 ppm, and 600 ppm concentration respectively. Following administration of NaF, there was significant increase in systolic pressure, diastolic pressure and mean arterial pressure. Markers of oxidative stress; malondialdehyde, hydrogen peroxide, advance oxidation protein products, and protein carbonyl were significantly increased in dose‐dependent pattern in the cardiac and renal tissues of rats together with significant decrease in the GST activity in NaF‐treated rats compared to the control. Also serum markers of inflammation, cardiac, and renal damage including myeloperoxidase, xanthine oxidase, blood urea nitrogen, creatinine, Lactate dehydrogenase (LDH), and Creatinine kinase myocardial band (CK‐MB) significantly increased indicating induction of oxidative stress, renal, and cardiac damage after exposure. Histopathology of the kidney and heart revealed aberrations in the histological architecture in NaF‐treated rats. Also, immunohistochemistry showed higher expression of nuclear factor kappa beta (NF‐kB) in the cardiac and renal tissues of rats administered NaF. Combining all, these results indicate NaF‐induced hypertension through generation of reactive oxygen species and activation of renal and cardiac NF‐kB expressions.

Alterations in blood pressure, antioxidant status and caspase 8 expression in cobalt chloride-induced cardio-renal dysfunction are reversed by Ocimum gratissimum and gallic acid in Wistar rats

The protective abilities of the chloroform extract of Ocimum gratissimum (COG) and gallic acid against cobalt chloride (CoCl2) - induced cardiac and renal toxicity were evaluated. Rats were exposed to CoCl2 (350ppm) for 7 days, either alone, or in combination with COG (100 and 200mg/kg) or gallic acid (120mg/kg). CoCl2 given alone, caused significant increases (p<0.05) in oxidative stress parameters (hydrogen peroxide, H2O2 and malondialdehyde, MDA) and increased expression of the apoptotic initiator caspase 8 in the heart and kidneys. There was significant reduction (p<0.05) in reduced glutathione (GSH) in cardiac and renal tissues; reduction in superoxide dismutase (SOD) activity in the kidneys and adaptive increases in Glutathione S-transferase (GST) and catalase (CAT). CoCl2 also produced significant reduction (p<0.05) in systolic (SBP), diastolic (DBP) and mean arterial (MAP) blood pressures. Oral COG and gallic acid treatment significantly reduced (p<0.05) the levels of H2O2 and MDA; with reduced expression of caspase 8 and restoration of GSH levels, GPx, SOD and CAT activities, howbeit, to varying degrees in the heart and kidneys. COG (200mg/kg) was most effective in restoring the blood pressures in the rats to near control levels. CoCl2-induced histopathological lesions including myocardial infarction and inflammation and renal tubular necrosis and inflammation were effectively ameliorated by the treatments administered. This study provides evidence for the protective roles of O. gratissimum and gallic acid by modulation of CoCl2-induced alterations in blood pressure, antioxidant status and pro-apoptotic caspase 8 in Wistar rats.

Phytochemical screening and toxicity studies on the methanol extract of the seeds of moringa oleifera

Abstract: The seeds of Moringa oleifera were collected, air-dried, pulverized, and subjected to cold extraction with methanol. The methanol extract was screened phytochemically for its chemical components and used for acute and sub-acute toxicity studies in rats. The phytochemical screening revealed the presence of saponins, tannins, terpenes, alkaloids, flavonoids, carbohydrates, and cardiac glycosides but the absence of anthraquinones. Although signs of acute toxicity were observed at a dose of 4,000 mg kg−1 in the acute toxicity test, and mortality was recorded at 5,000 mg kg−1, no adverse effect was observed at concentrations lower than 3,000 mg kg−1. The median lethal dose of the extract in rat was 3,873 mg kg−1. Sub-acute administration of the seed extract caused significant (p<0.05) increase in the levels of alanine and aspartate transferases (ALT and AST), and significant (p<0.05) decrease in weight of experimental rats, at 1,600 mg kg−1. The study concludes that the extract of seeds of M. oleifera is safe both for medicinal and nutritional uses.

Taurine enhances spermatogenic function and antioxidant defense mechanisms in testes and epididymis of L-NAME-induced hypertensive rats

The beneficial health effects of taurine on hypertension have been demonstrated previously in both experimental and epidemiological studies. However, the role of taurine in reproductive dysfunction associated with hypertension has not been investigated. The present study evaluated the therapeutic efficacy of taurine on reproductive deficits in N-nitro-l-arginine methyl ester (L-NAME)-induced hypertensive rats. Sixty male Wistar rats were randomly assigned into six groups namely control, taurine alone, L-NAME alone (40mg/kg) or L-NAME treated with either taurine (100 and 200mg/kg) or reference drug atenolol (10mg/kg) for 28 consecutive days. Results indicated that taurine treatment significantly abrogated L-NAME-induced increase in systolic, diastolic and mean arterial pressures when compared with hypertensive control. Administration of taurine markedly increased antioxidant enzymes activities and glutathione level whereas it suppressed the increase in biomarkers of oxidative stress in the testes and epididymis of L-NAME-induced hypertensive rats. Moreover, taurine significantly reversed hypertension mediated decreases in circulatory concentrations of luteinizing hormone, follicle-stimulating hormone and testosterone whereas it increased testicular sperm number, epididymal sperm number and sperm progressive motility in the hypertensive rats. Furthermore, taurine abrogated the suppression of marker enzymes of testicular function namely acid phosphatase, alkaline phosphatase and lactate dehydrogenase and preserved the histo-architectures of the testes and epididymis in L-NAME-induced hypertensive rats. Taken together, the findings from this study highlight the beneficial role of taurine in reproductive system of L-NAME-induced male hypertensive rats. Taurine supplementation may be a good clinical approach to prevent reproductive deficits in male hypertensive patients.

Original article. Mitigation of diazinon-induced cardiovascular and renal dysfunction by gallic acid

Abstract Studies of the link between environmental pollutants and cardiovascular dysfunction, neglected for decades, have recently provided new insights into the pathology and consequences of these killers. In this study, rats were divided into four groups, each containing 10 rats. The rats in group one served as controls and were administered normal saline, whereas the rats in group two were orally gavaged with 3 mg/kg of diazinon (DZN) alone for twenty one consecutive days. The rats in groups 3 and 4 were administered respective 60 mg/kg and 120 mg/kg gallic acid (GA) in addition to DZN for twenty one consecutive days. Exposure of rats to diazinon significantly (p<0.05) reduced the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) content. Malondialdehyde, hydrogen peroxide (H2O2) and nitric oxide (NO) contents were also significantly (p<0.05) elevated following DZN exposure. DZN further caused a significant (p<0.05) decrease of heart rate and QT interval prolongation. Hematologic analysis revealed significant reduction (p<0.05) in packed cell volume (PCV), hemoglobin concentration (Hb), red blood cell (RBC) count, and total white blood cell count of rats administered only DZN. Observations in this study suggest a modulatory role of gallic acid in diazinon-induced anemia and associated cardiovascular dysfunction in rats. Treatment with gallic acid reversed the oxidative stress markers studied, increased the antioxidant defence system and reduced deleterious effects on hematological parameters in rats. Pathologic findings of the heart and kidney were also found to be lessened.

Modulatory effects of melatonin and vitamin C on oxidative stress-mediated haemolytic anaemia and associated cardiovascular dysfunctions in rats

Abstract Background Phenylhydrazine (PHE) in experimental animal models has been widely reported to cause haemolytic anaemia, via the induction of oxidative stress and thus causing deleterious cardiovascular complications. Hence, this study was designed to evaluate the possible modulatory role of melatonin (MLT) or vitamin C when co-administered with PHE. Methods Anaemia was established with PHE administration. MLT or vitamin C was co-administered with PHE. Haematological parameters, markers of oxidative stress, enzymic and non-enzymic antioxidants, blood pressure and electrocardiograms were assessed. Results PHE administration led to a significant (p<0.05) increase in malondialdehyde (MDA), and hydrogen peroxide (H2O2) generated in cardiac, renal and red blood cell (RBC) lysates. PHE also significantly reduced the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD) and reduced glutathione (GSH) contents, respectively. The RBC counts, haemoglobin (Hb) concentration and packed cell volume (PCV) were also significantly reduced following the administration of PHE. Furthermore, the systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MABP) increased significantly in rats administered PHE alone. Similarly, PHE administration led to a significant drop in heart rate but prolonged QRS, QT and QTc interval. Pathology of the heart and kidney was also observed in PHE treated group. However, treatment with MLT and vitamin C improved enzymic and non-enzymic antioxidant system together with the restoration of SBP, DBP and MABP to near normal. The architectural anarchy observed in the heart and kidney of PHE administered rats was reversed to some extent. Conclusions Hence, MLT and vitamin C could be employed as therapeutic targets in various cardiovascular diseases and its complications.

Ameliorative effect of gallic acid on doxorubicin-induced cardiac dysfunction in rats

Abstract Background: The use of doxorubicin (DOX) as an antineoplastic agent has been greatly limited because of the myriad of toxic sequelae associated with it. The aim of this study was to assess the protective effects of gallic acid (GA) on DOX-induced cardiac toxicity in rats. Methods: Sixty male rats (Wistar strain) were used in this study. They were divided into six groups (A–F) each containing 10 animals. Group A was the control. Rats in Groups B, C, and D were treated with DOX at the dosage of 15 mg/kg body weight i.p. Prior to this treatment, rats in Groups C and D had been treated orally with GA for 7 days at the dosage of 60 and 120 mg/kg, respectively. Animals from Groups E and F received only 60 and 120 mg/kg GA, respectively, which were administered orally for 7 days. Results: The exposure of rats to DOX led to a significant (p<0.05) decrease in the cardiac antioxidant defence system and elevation of creatine kinase myocardial band and lactate dehydrogenase. The electrocardiography results showed a significant decrease in heart rate, QRS, and QT-segment prolongation. GA alone improved the antioxidant defence system. Conclusions: The GA pretreatment significantly alleviated GA-associated ECG abnormalities, restored the antioxidant status and prevented cardiac damage.

Antidiabetic and antioxidant effects of Croton lobatus L. in alloxan-induced diabetic rats.

Background: Croton lobatus contains a high amount of antioxidant phytochemicals that probably account for its wide use as food and medicine in the traditional communities of West Africa. Methods: The study evaluated the modulatory role of methanol extract of Croton lobatus leaf on alloxan-induced diabetes and associated cardiovascular complications. Male rats were randomly selected and assigned to one of six groups (A to F) of eight animals each: A (distilled water); B (corn oil); C (Alloxan); D (Alloxan + 100 mg kg-1 Croton lobatus); E: (Alloxan + 200 mg kg-1 C. lobatus); and F (Alloxan + 100 mg kg-1 glibenclamide). Results: Acute toxicity studies revealed no mortality of rats at the administration of different doses of extract up to the 5,000 mg kg-1 dose. Histology of the pancreas showed focal area of necrosis, and fatty infiltration in diabetic untreated rats, but these lesions were absent in pancreas of rats treated with C. lobatus extract. Conclusion: Methanol leaf extract of C. lobatus reduced arteriogenic risk factors, improved antioxidant status, restored the observable pathological lesions associated with experimental diabetes in rats, and thus offers a new therapeutic window as herbal therapy for the treatment of diabetes mellitus and associated cardiovascular complications.

Ameliorative effect of Azadirachta indica on sodium fluoride-induced hypertension through improvement of antioxidant defence system and upregulation of extracellular signal regulated kinase 1/2 signaling

Abstract Background: Toxicities due to fluoride exposure from natural and industrial sources occur commonly in man and animals with severe consequences ranging from mild cardiac derangements to sudden death. In this study, we investigated the protective effects of the methanol extract of Azadirachta indica (AI) against sodium fluoride (NaF)-induced hypertension and genotoxicity in rats. Methods: Sixty rats were divided into six groups of ten rats each as follows: Group A, the control group received distilled water; Group B rats were administered NaF at 600 ppm in drinking water; Groups C and D rats were pre-treated with the methanol extract of AI and thereafter administered NaF at 600 ppm in drinking water for 7 consecutive days; Groups E and F rats were co-administered with AI and NaF. Results: The administration of NaF caused significant (p<0.05) increases in the blood pressure, markers of oxidative stress, serum myeloperoxidase, xanthine oxidase values in NaF-alone treated rats, compared with the control. Significant (p<0.05) decreases were observed in cardiac and renal antioxidant defence system in rats administered NaF alone compared with the control group. NaF treatment also resulted in a reduction in the expressions of extracellular signal-regulated kinase (ERK) 1/2 in cardiac and renal tissues of NaF-treated rats. Moreover, NaF treatment elicited an increase in the frequency of micronucleated polychromatic erythrocytes when compared with the control group. Conclusions: This study shows the protective effect of AI on NaF-induced hypertension and genotoxicity through antioxidant and ERK 1/2 signaling in rats.

Polyphenol-Rich Fraction of Parquetina nigrescens Mitigates Dichlorvos-Induced Cardiorenal Dysfunction Through Reduction in Cardiac Nitrotyrosine and Renal p38 Expressions in Wistar Rats

ABSTRACT Parquetina nigrescens is commonly used to treat diseases in humans and animals in developing countries, including Nigeria. This study evaluates the effects of its polyphenol-rich fraction (prf) on dichlorvos-induced cardio- and renal toxicity. There were several factors assessed during this study, including cardiac and renal markers, serum myeloperoxidase and xanthine oxidase, and electrocardiograph (ECG) changes. The changes in electrocardiograph (ECG) were recorded. Immunohistochemistry of cardiac and renal p38 and nitrotyrosine was determined. Dichlorvos exposure caused a significant decrease in L-glutathione (reduced glutathione) and other antioxidant enzymes with increases in malondialdehyde, myeloperoxidase, advanced oxidation protein products, and protein carbonyl levels. It also brought about alterations in microanatomy of the heart and kidneys accompanied by increases in serum creatinine and urea levels. Exposure to dichlorvos induced prolonged QRS interval and shortened QT durations in rats. Immunohistochemistry revealed lower expressions of cardiac nitrotyrosine and renal p38 (mitogen-activated protein kinase; MAPK) in rats treated with prf of P. nigrescens. Combining all, prf of P. nigrescens demonstrated antioxidant as well as protective properties in the heart and kidneys of rats exposed to dichlorvos. It ameliorated dichlorvos-induced cardio- and nephrotoxicity giving credence to its use in ethnomedicine.