Novel sedentary cage induced sedentariness in rats: evidence from relevant biomarkers.

BACKGROUND: Sedentary behavior or physical inactivity is considered a foremost contributor to the rise in obesity and overweight and a risk factor for several non-communicable diseases. However, its effect on the etiopathogenesis of some diseases is underestimated in both developed and developing countries worldwide. The present study designed a novel sedentary cage with a view to achieving sedentariness in rats, and also investigated the effectiveness of the cage in achieving sedentariness by assessing some markers of cardiometabolic risks in Wistar rats. METHODS: Adult male Wistar rats were divided into 3 groups of six rats. Rats in Group 1 were the control. The sedentary groups were 4-hr. sedentary and 8-hr. sedentary. The sedentary rats were subjected to restrained movements for 4 and 8 hours daily in the sedentary cage for 3 months. Anthropometric indices, food consumption and blood pressure parameters of the rats were measured. Microalbuminuria and serum glucose, uric acid, albumin, nitric oxide, endothelin-1, insulin, inflammatory markers were also Measured. RESULTS: Results indicated significant increases in body weight, BMI, Lee index, food consumption, systolic and diastolic pressure and decrease in serum nitric oxide bioavailability in the 8-hr sedentary rats. There were also significant increases in serum glucose, uric acid, endothelin-1, insulin, CRP and microalbuminuria in the 8-hr. sedentary rats in comparison with the control. The interleukin-6 and TNF-α also revealed a significant increase in the 8-hr. sedentary rats compared with the control. However, there was no significant difference in cortisol level across all the groups. CONCLUSIONS: We concluded that the novel sedentary cage successfully caused sedentariness in the rats as evident by the alteration in the cardiometabolic health in the rats, especially the group that were made sedentary for 8 h.

Polyphenol-rich extract of Ocimum gratissimum leaves prevented toxic effects of cyclophosphamide on the kidney function of Wistar rats.

BACKGROUND: Cyclophosphamide (CP) is one of the potent and low cost chemotherapy used in clinical setting against a variety of tumors. However, its association with nephrotoxicity limits its therapeutic use. Ocimum gratissimum leaf is a medicinal plant with numerous pharmacological and therapeutic efficacies, such as antioxidant, anti-inflammation, and anti-apoptotic properties. METHODS: The present study was designed to evaluate the protective effect of Ocimum gratissimum (OG) against CP-induced kidney dysfunction in rats. Rats were pre-treated with 400 mg/kg b.w. of leave extract of Ocimum gratissimum (Ocimum G.) for 4 days and then 50 mg/kg b.w. of CP was co-administered from day 5 to day 7 along with Ocimum G. Markers of renal function and oxidative stress, food and water intake, electrolytes, aldosterone, leukocytes infiltration, inflammation and histopathological alteration were evaluated. RESULTS: Obvious renal inflammation and kidney injuries were observed in CP treated groups. However, administration of leave extract of Ocimum G. prevented oxidative stress, kidney injuries, attenuated inflammation, increased aldosterone production and reduced sodium ion and water loss in rats. The plasma creatinine, urea and urine albumin concentration were normalized after the administration of Ocimum G. extract in rats treated with CP. Ocimum G. also decreased the plasma concentrations of Interleukin-(IL)-6, C-reactive protein and activity of myeloperoxidase and malondialdehyde in CP treated rats. CONCLUSION: Ocimum G. prevented kidney injury and enhanced renal function via inhibiting inflammation and oxidant-induced CP toxicity. The efficacy of Ocimum G. is related to the presence of various phytochemicals in the plant.

Kolaviron Diminishes Diclofenac-Induced Liver and Kidney Toxicity in Wistar Rats Via Suppressing Inflammatory Events, Upregulating Antioxidant Defenses, and Improving Hematological Indices.

Diclofenac (DF) is widely used in the treatment of pain and fever. Despite it therapeutic benefits, it triggered hepatorenal injury. Thus, the present study investigated the protective roles of kolaviron (KV) against DF-induced hepatic and renal toxicity in rats. The rats were allotted into groups: control group received propylene glycol and treatment groups received DF, which induced hepatorenal toxicity in rats and different doses of KV that prevented systemic toxicity of DF in rats. Twenty-four hours after the last treatment, all the rats were killed. Pro-inflammatory levels, markers of liver and kidney functions, oxidative stress, hematological indices, and histopathological alterations were evaluated. Diclofenac caused significant increase in the plasma levels of creatinine and urea and activities of liver enzymes, including bilirubin level, pro-inflammatory markers, and plasma prostaglandin E2 (PGE2). It also caused significant alteration in renal and hepatic PGE2, antioxidants, lipid peroxidation (malondialdehyde), and hematological indices. These toxic effects were confirmed by histological studies and levels of inflammatory infiltration (myeloperoxidase). However, KV significantly prevented or reduced the adverse effects of DF in the plasma, liver, and kidney of the rats pretreated with KV before DF administration. This study showed the efficacy of KV as hepatic and renal protector in DF-induced hepatorenal toxicity through reduction of oxidative stress and suppression of inflammation.

Effect of fatty acids from ethanol extract of Moringa oleifera seeds on kidney function impairment and oxidative stress induced by gentamicin in rats.

Gentamicin, an aminoglycoside drug, used for the treatment of Gram-negative bacterial infections. Despite its potency against bacterial infections, its clinical use is limited owing to nephrotoxicity effect. However, the study investigated the nephroprotective effect of fatty acids from ethanolic extract of Moringa oleifera seeds (EEMOS) against gentamicin-induced kidney injury in rats. Forty-five male Wistar rats, 100-160 g, were divided into 5 groups as follows: Group 1 (control), 5 rats, received 0.2 ml/100 g/day of propylene glycol orally for 28 days. Group 2, 10 rats, received 100 mg/kg/day (i.p) of gentamicin (GENT) for 8 days. Group 3-5, 10 rats each, treated with EEMOS orally for 28 days at graded doses of 100, 200 and 400 mg/kg respectively after GENT treatment. Twenty four after treatment, five rats from each group were sacrificed. The remaining 5 rats were sacrificed after 2 weeks recovery period from the drugs. The result showed that GENT elicited polyuria, elevated plasma creatinine, urea, and lower plasma electrolytes and creatinine clearance levels. Measurements of 24 h urinary output demonstrated marked decrease in creatinine and potassium levels in the GENT-treated group, whereas sodium level remain unchanged. Also, GENT caused significant decrease in superoxide dismutase and an increase in malondialdehyde levels in the kidney of the rats. Histopathological examination revealed evidence of necrosis of the kidney. Treatment with EEMOS significantly ameliorated the alterations caused by GENT in the plasma, urine and kidney homogenate of the rats. Hence, the mono- and poly-unsaturated fatty acids present in EEMOS were responsible for its renoprotective ability.

Protective Effects of Methanol Extract of Vernonia amygdalina (del.) Leaf on Aspirin-Induced Gastric Ulceration and Oxidative Mucosal Damage in a Rat Model of Gastric Injury.

This study investigated the quantitative polyphenolic constituents and gastroprotective effects of methanol extract of Vernonia amygdalina leaf (MEVA) against aspirin-induced gastric ulcer in rats. Ulceration was induced by 3 days' oral administration of aspirin (150 mg/kg body weight). Wistar rats were pretreated with cimetidine (reference drug) at a dose of 100 mg/kg body weight and MEVA at 200, 300, and 400 mg/kg body weight once daily for 28 days prior to ulcer induction. At the end of the experiment, gastric secretions, antioxidant status, and histopathological alteration were evaluated. We observed that the significantly increased ulcer index, gastric volume, free and total acidity, malondialdehyde level, and pepsin activity were effectively reduced following treatment with 200 and 300 mg/kg MEVA. The extract also markedly attenuated the reduced activity of superoxide dismutase and reduced glutathione level as well as pH and mucin content in the ulcerated rats. Administration of the extract also significantly attenuates necrosis of the stomach tissue of the ulcerated rats. The results suggested that the MEVA leaf, preferably at 200 and 300 mg/kg body weight, ameliorated aspirin-induced gastric ulceration via antioxidative and H2 receptor antagonist.

Kolaviron attenuates diclofenac-induced nephrotoxicity in male Wistar rats.

The beneficial effects of kolaviron, a natural biflavonoid from the seeds of Garcinia kola, have been attributed to its antioxidant and anti-inflammatory activities. This study was designed to investigate the renoprotective effect of kolaviron in rat model of diclofenac (DFC)-induced acute renal failure. Thirty-five male Wistar rats were divided into 7 groups of 5 rats each as follows: a control group that received propylene glycol orally and treatment groups that received DFC, DFC recovery, DFC followed by kolaviron at 3 different doses, and kolaviron only. DFC-treated rats showed sluggishness, illness, and anorexia. Their urine contained appreciable protein, glucose, and ketone bodies. Histopathological examination of their kidneys revealed profound acute tubular necrosis. DFC treatment significantly increased levels of plasma creatinine, urea, sodium, chloride, potassium ions, and increased renal tissue activities of superoxide dismutase, catalase, levels of malondialdehyde, and hydrogen peroxide. Fractional excretion of sodium and potassium and renal tissue levels of reduced glutathione and prostaglandin E2 (PGE2) decreased significantly in DFC-treated groups. However, kolaviron administration significantly reduced the toxic effect of DFC on PGE2 release; plasma levels of creatinine, urea, glucose, and electrolytes; and significantly attenuated renal tubular and oxidative damages. Furthermore, the effects of DFC administration on food consumption, water intake, urine output and urine protein, glucose, ketone bodies, and electrolytes were significantly attenuated in animals treated with kolaviron. The results suggested that kolaviron ameliorated DFC-induced kidney injury in Wistar rats by decreasing renal oxidative damage and restoration of renal PGE2 release back to the basal levels.

Polyphenol-rich extract of Ocimum gratissimum leaves ameliorates colitis via attenuating colonic mucosa injury and regulating pro-inflammatory cytokines production and oxidative stress.

Colitis is a chronic inflammation and ulcer on the inner lining of the large intestine. For many centuries Ocimum gratissimum (OG) leaves have been used in folk medicine in Nigeria to treat inflammatory bowel diseases, however, to date, the anti-colitis effects of OG have not been scientifically proven. In this study we investigated the effects of polyphenol rich extract of Ocimum gratissimum (PREOG) leaf on colonic mucosa injury in colitis, its mechanisms, initial administration time and dosage. Dextran sodium sulfate (DSS)-induced rat colitis models was used. PREOG administration was initiated at 3 and 7 d after the model was established at doses of 200, 400 and 800 mg/kg for 7 d. 5-aminosalicylic acid (5-ASA) was used as a reference drug. The disease activity index (DAI), vascular permeability, markers of oxidative stress, granulocyte infiltration, inflammation and histopathological alteration were evaluated. Obvious colonic inflammation and mucosa injuries were observed in DSS-induced colitis groups. PREOG administration promoted repair of colonic mucosa injuries, attenuated inflammation, and decreased DAI scores in rats with colitis. PREOG also decreased the plasma concentrations of Interleukin-(IL)-6 and tumor necrosis factor (TNF)-α, and concentrations of myeloperoxidase, nitric oxide, cyclooxygenase-2 and malondialdehyde in the colon, and increased the plasma concentrations of IL-4 and IL-10 as well as the concentration of superoxide dismutase, catalase and reduced glutathione in the colon. The efficacy of PREOG was dosage dependent. In conclusion, OG repairs colonic mucosa injury in experimental colitis through its ant-inflammatory and ant-oxidant. Its efficacy related to initial administration time and dose.

Ocimum gratissimum Ameliorates Gentamicin-Induced Kidney Injury but Decreases Creatinine Clearance Following Sub-Chronic Administration in Rats.

The effects of aqueous extract of Ocimum gratissimum leaf (AOGL) on the renal function of rats with gentamicin-induced nephrotoxicity were investigated. This study involved the use of forty five (45) adult male Wistar rats (housed in separate metabolic cages) such that graded doses of OAGL were administered to the experimental groups (p.o.) for 28 days after exposure to gentamicin toxicity (100 mg/kg i.p.) for 1 week. At the end of the study, comparisons of some indices of renal function as well as antioxidant status (GSH and TBARS) were made between the control, toxic and AOGL-treated groups at P < 0.05. The result showed that gentamicin treatment caused significant increase ( P < .05) in urine output, urea, creatinine, total protein, relative kidney weight, and TBARS, as well as significant decrease ( P < .05) in urine creatinine and GSH levels. Post-treatment with graded doses of AOGL caused significant increase in food consumption, GSH, urine, and plasma creatinine, as well as significant decrease ( P < .05) in relative kidney weight, TBARS, and urine total protein. There was an appreciable difference in the kidney histology of the AOGL-treated groups when compared with the toxic control. Hence, the extract has therapeutic potential in the management of gentamicin-induced kidney injury, although a risk profile of renal dysfunction is not unlikely from 28 days of administration as evident by the decrease in creatinine clearance.

Assessment of the Effects of Graded Doses of Polyphenolic-Rich Fraction of Garcinia kola Seeds on Pituitary-Testicular Axis of Male Wistar Rats.

This study evaluated the ameliorative and prophylactic effects of 2 different doses of polyphenolic-rich fraction of Garcinia kola (PPRFGk) seeds on the histology and hormones of pituitary-testicular axis of male Wistar rats. Thirty-five male Wistar rats (150-200 g) were divided into 7 groups of 5 rats each. Groups I and II were given distilled water (0.5 mL/day) for 8 days followed by propylene glycol (0.2 mL/d) and 600 mg/kg of PPRFGk, respectively, for 21 days. Group III received sodium arsenate (8 days), left untreated for 21 days. Groups IV and V received sodium arsenate (20 mg/kg) for 8 days followed by PPRFGk (300 and 600 mg/kg, respectively) for 21 days. Groups VI and VII received PPRFGk (300 and 600 mg/kg, respectively) for 21 days followed by sodium arsenate (20 mg/kg) for 8 days. Rats were killed by cervical dislocation 24 hours after the last dose and their blood collected through cardiac puncture. Blood sera were assayed for the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone using immunoassay techniques. Histology of the pituitary gland and testes was carried out. A significant reduction was observed in the concentration of FSH in groups IV, V, VI, and VII in comparison with groups I and II. The concentrations of both LH and testosterone showed significant decreases in groups IV, V, VI, and VII in comparison with group I. Group III presented with the lowest serum hormonal concentrations. Photomicrographs of the pituitary gland revealed greatly reduced basophils in group III and mildly reduced basophils in groups IV, VI, and VII in comparison with groups I and II. Group V revealed hypercellularized and distorted basophils. Photomicrographs of the testes showed detachment of the seminiferous tubules from the basement membrane and disruption of the interstitial space which was worse in group III, moderate in groups V and VI, and mild in group VII. In conclusion, PPRFGk effected a dose-dependent reversal and prevention of the perturbations caused by arsenate in rats.

Gastro-protective effect of methanol extract of Vernonia amygdalina (del.) leaf on aspirin-induced gastric ulcer in Wistar rats.

This study investigated the protective effects of methanol extract of Vernonia amygdalina leaf (MEVA) on aspirin induced gastric ulcer in rats. Thirty Wistar rats, 150-200 g were divided into six groups as follows: Group 1 (control) rats received 2 mL/kg of propylene glycol for 28 consecutive days. Group 2 (Ulcer Control) received 150 mg/kg/day of aspirin suspended in 3 mL of 1% carboxymethylcellulose in water orally for 3 consecutive days during which the rats were fasted for the induction of ulcer. Group 3 received cimetidine at 100 mg/kg/day orally for 28 consecutive days and thereafter treated as group 2. Groups 4, 5 and 6 received MEVA orally at 200, 300 and 400 mg/kg/day respectively for 28 consecutive days and thereafter were treated with aspirin as group 2. All the animals were sacrifice at the end of the study to determine the gastric pH, gastric acidity, gastric ulcer score, haematological indices, superoxide dismutase (SOD) activity, reduced glutathione (GSH) and Lipid peroxidation (LPO) levels. The result showed that aspirin significantly (p < 0.05) increased gastric ulcer score and index, decreased gastric pH, gastric acidity, SOD activity, GSH level as well as increased LPO level. It induced significant necrosis of the stomach tissue. Administration of MEVA significantly (p < 0.05) increased gastric pH, but decreased gastric acid secretion and reversed alteration of haematological parameters. It also significantly (p < 0.05) increased SOD activity, GSH level and decreased LPO level. The results suggest that Vernonia amygdalina possesses gastro-protective properties against aspirin-induced gastric ulcer.

The role of electrocardiogram in the diagnosis of dextrocardia with mirror image atrial arrangement and ventricular position in a young adult Nigerian in Ile-Ife: a case report.

INTRODUCTION: Dextrocardia with situs inversus is a rare congenital disease. In patients with this condition, the heart is presented as a mirror image of itself with its apex pointing to the right. The pulmonary and abdominal anatomies are reversed. Dextrocardia with situs inversus occurs at birth but its diagnosis may be in adulthood. This case advances knowledge by graphically describing the unusual electrocardiographic features of dextrocardia in a young adult. CASE PRESENTATION: We report a case of a 22-year-old Nigerian man of Yoruba ethnicity who presented himself for preadmission medical test. He had a standard 12-lead electrocardiogram which revealed uncommon features: inversion of P waves in leads I, aVL and aVR; dominantly negative QRS waves in leads I, V1 to V6; reverse R wave progression in chest leads; low voltage in V4 to V6; extreme QRS axis; flattened T waves in V4 to V6 and aVR; and inverted T waves in lead I and aVL. An electrocardiogram diagnosis of dextrocardia was made. The differential diagnosis considered was right ventricular hypertrophy. A cardiovascular examination showed pulse rate of 70 beats per minute, blood pressure of 119/62mmHg, visible cardiac impulse at right precordium, apex beat was located at his fifth right intercostal space mid-clavicular line. A chest X-ray (posterior anterior view) including upper abdomen showed dextrocardia; his aortic arch was located on the right. His stomach bubble was located below his right hemidiaphragm. His trachea was slightly deviated to the left. The findings in his lung fields were not remarkable. Abdominopelvic ultrasonography showed that right-sided intra-abdominal organs (liver, gallbladder) were located on the left while left-sided organs (stomach, spleen) were located on the right. His abdominal aorta was on the right while his inferior vena cava was located on the left. A diagnosis of dextrocardia with situs inversus was made ultrasonographically. CONCLUSIONS: A properly interpreted electrocardiogram was useful in suspecting the diagnosis of dextrocardia with situs inversus. So, an analysis of a relatively simple and non-invasive diagnostic tool such as an electrocardiogram allows for suspicion of a cardiovascular anomaly in a setting of scarce diagnostic resources.

Amelioration of Cadmium-Induced Nephropathy using Polyphenol-rich Extract of Vernonia amygdalina (Del.) Leaves in Rat Model.

AIM: To determine the effects of polyphenol-rich extract of the leaves of Vernonia amygdalina (PEVA) in rats with Cd-induced nephropathy. MATERIALS AND METHODS: Sixty five male Wistar rats were divided into five groups as follows; Group 1 received distilled water throughout the period of study. Group 2 received 5 mg/kg body weight of cadmium (Cd), in the form of CdSO4, for five consecutive days via intraperitoneal route. Groups 3, 4 and 5 were pretreated with Cd as group 2 and thereafter received oral treatment of PEVA for 4 weeks at 100 mg/kg, 200 mg/kg and 400 mg/kg body weight, respectively. RESULTS: Exposure to Cd toxicity significantly induced deleterious alterations in plasma and urine levels of creatinine, urea and glucose as well as creatinine and urea clearance (p < 0.05) in the rat model. There was a significant disturbance in the antioxidant system as revealed by the levels of thiobarbituric acid reactive substance (TBARS) and reduced glutathione (GSH) (p < 0.05) in the kidney tissue of the rats. With marked improvements in renal histoarchitecture, PEVA treatment showed a duration and non dose-dependent ameliorative potential. CONCLUSION: PEVA treatment reversed the compromise of renal function that was induced by Cd toxicity in rat model.

Effect of fractionated extracts and isolated pure compounds of Spondias mombin (L. Anacardiaceae) leaves on novelty-induced rearing and grooming behaviours in mice.

This study attempted to elucidate the neurotransmitter systems involved in the neurophysiological properties of ethanolic extract, fractions and pure isolates of Spondias mombin leaves in mice (n = 6) after intraperitoneal (i.p.) route of administration.The crude ethanolic extract of Spondian mombin leaves was fractionated using the partitioning method to obtain the ethylacetate, butanolic and aqueous fractions. Open column chromatographic fractionation of the ethylacetate fraction yielded seven sub-fractions, out of which the pure coumaroyl, quercetin and gallic acid derivatives were obtained after purification on Sephadex LH 20. The ethanolic extract, butanolic fraction, ethylacetate subfractions and pure isolates of the Spondian mombin leaves were tested on novelty-induced rearing and grooming behaviours in mice with standard pharmacological tools using the open field method. The extract and its fractions decreased novelty-induced rearing in a dose-dependent manner. While the Coumaroyl derivative had no effect on novelty-induced rearing, it significantly reversed the inhibitory effect of yohimbine, propranolol and haloperidol on novelty-induced rearing. Quercetin significantly potentiated the inhibitory effect of yohimbine on novelty-induced rearing. Naloxone significantly potentiated the quercetin-induced suppression of novelty-induced rearing. Gallic acid derivative significantly potentiated the inhibitory effect of yohimbine on novelty-induced rearing. Naloxone, atropine and haloperidol pretreatments significantly potentiated gallic acid derivative-induced suppression of novelty-induced rearing.The extract and its fractions had biphasic effect on novelty-induced grooming in mice. Coumaroyl derivative significantly increased novelty-induced grooming, while quercetin and gallic acid derivative decreased novelty-induced grooming significantly. The three pure isolates significantly reversed the effects of yohimbine and atropine on the novelty-induced grooming in mice. Propranolol-induced increase in novelty-induced grooming was significantly reversed by coumaroyl and gallic acid derivatives. Pre-treatment with naloxone significantly increased the gallic acid derivative-induced suppression of novelty-induced grooming. Pre-treatment with haloperidol reversed the effect of coumaroyl derivative and potentiated the inhibitory effect of quercetin derivative and gallic acid derivative significantly. This study suggested that adrenergic and dopaminergic neuro-transmissions are strongly involved in the neural mechanisms of the effect of the three pure isolates derivative, while opioid neuro-transmission is strongly linked with the neural mechanism of behavioural effect of coumaroyl derivative.

Sedative, antiepileptic and antipsychotic effects of Spondias mombin L. (Anacardiaceae) in mice and rats.

In this study, we evaluated the effects of air-dried Spondias mombin leaves extracted with aqueous, methanol and ethanol solvents on hexobarbital-induced sleeping time and novelty-induced rearing (NIR) behaviours in mice and rats. We also studied the effect of the extracts on amphetamine- and apomorphine-induced stereotyped and picrotoxin-induced convulsive behaviour in rats. All residues from different extractions were dissolved in normal saline and administered intraperitoneally (i.p.). The methanolic and ethanolic extracts (12.5-100mg/kg i.p.) prolonged the hexobarbital-induced sleeping time and reduced the NIR in both mice and rat in a dose-dependent manner. The aqueous extract prolonged the hexobarbital-induced sleeping time and reduced (NIR) at doses of 50 and 100mg/kg. The inhibitory effect of the extracts on NIR was not reversed by atropine, yohimbine, naltrexone and flumazenil. However, the extracts blocked the facilitating effect of flumazenil. This suggests that NIR inhibitory effects of extracts of Spondia mombin are not mediated via muscarinic, alpha(2) adrenergic, and mu-opioid receptors, whereas, the extracts appear to facilitate GABAergic transmission. In addition the extracts blocked picrotoxin-induced convulsions. Phenolic compound(s) were present in the ethanolic and methanolic extracts, which exhibited anticonvulsant properties in the picrotoxin-induced convulsions model. The extracts decreased the amphetamine/apomorphine-induced stereotyped behaviour, which suggest that these extracts possess antidopaminergic activity. The effect of the extracts on hexobarbitone-induced sleeping time was blocked by flumazenil a GABA(A) antagonist, indicating that the extracts contain GABA(A) agonists. These results suggest that the leaves extracts of Spondias mombin possess sedative and antidopaminergic effects.