Oral acute and sub-chronic toxicity assessment of aqueous leaf extract of Simarouba glauca DC (Paradise tree).

Simarouba glauca has been widely reported to be effective against a number of diseases and possesses medicinal benefits. Thus, the study was conducted to evaluate the toxic effect of aqueous leaf extract of Simarouba glauca (AESG) on relevant organs of male Wistar rats. The oral acute toxicity of AESG was evaluated according to the method described by Lorke. Sub-chronic toxicity of AESG was carried out in line with the guidelines of the Organization for Economic Co-operation and Development (OECD), using a total of twenty-four (24) male Wistar rats divided into four groups of six rats each. Test rats were orally administered AESG at doses of 500, 1000 and 2000 mg /kg body weight, respectively, daily for thirty (30) days. At the end of the study, rats were fasted overnight and sacrificed; the relevant biochemical and histopathology evaluation was carried out. Statistical analysis was conducted using the GraphPad Prism®, version 7. The data obtained indicated that the LD50 exceeded 5000 mg/kg. There were significant increases (P < 0.05) in percentage (%) body weight of test rats. There were no significant differences (P < 0.05) in mean liver, kidney, and heart weight/body weight (IOW/BWT) ratios. The AST activity was significantly lowered (P < 0.05) in rats administered AESG 2000 mg/kg. The ALP activities were significantly elevated (P < 0.05), while the GGT activities were significantly lowered (P < 0.05) in all groups of rats administered AESG. Plasma conjugated and unconjugated bilirubin were significantly lowered and elevated (P < 0.05), respectively in rats administered AESG 1000 and 2000 mg/kg. Plasma urea was significantly elevated (P < 0.05) in rats given AESG 1000 mg/kg. Test rats given AESG 2000 mg/kg recorded significant reduction (P < 0.05) in plasma sodium ions concentration. Rats given AESG 500 mg/kg recorded significant reduction (P < 0.05) in plasma bicarbonate ion levels. The findings suggest that AESG was not significantly toxic to the liver, kidney, and heart.

Renal effects of glucose transporter 4 in Nω-nitro-L-arginine/ /high salt-induced hypertensive rats.

OBJECTIVES: The aim of study was to determine the renal effects of glucose transporter 4 (GLUT4) in a hypertensive nephropathy rat model. BACKGROUND: GLUT4 has been implicated in insulin resistance and hypertension in several animal models; however its role in hypertensive nephropathy still remains unclear. METHODS: Hypertensive nephropathy was induced by Nω-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthase inhibitor, 100 mg/ml in drinking water and high salt (HS) diet (4 % NaCl), for 15 days in the presence of insulin, a GLUT 4 agonist (1 U/day) and indinavir, a GLUT4 inhibitor (80 mg/kg/day). RESULTS: Decreased basal renal medullary and cortical blood flow was enhanced in LNNA/HS/indinavir group (p < 0.01) but attenuated (p < 0.05) by insulin. Proteinuria was increased (p < 0.01) in LNNA/HS/indinavir group but attenuated (p < 0.01) by insulin. Insulin-treated rats decreased urine NO (p < 0.01) and urine Na2+ (p < 0.01) compared to other treated animals. In indinavir-treated animals, urine Na2+ was increased by benzamil, an epithelial sodium channel (ENaC) inhibitor (p < 0.01) and hydrochlorothiazide, a sodium/chloride co-transporter (NCC) inhibitor (p < 0.05). CONCLUSION: GLUT4 exerts a renoprotective role which may be related to increase NO production. The antinatriuretic effects of GLUT4 appear to be due to enhancement of ion transport activity of ENaC and NCC at the renal tubules (Fig. 9, Ref. 34).

In vitro determination of the uterine stimulatory effect of the aqueous leaf extract of Ficus exasperata.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Ficus exasperata Vahl (Moraceae) are used by traditional healers in Southern Nigeria to arrest pre-term contractions and are also used as an abortifacient in some parts of Africa. AIM OF STUDY: An earlier study on the aqueous leaf extract of Ficus exasperata (AET) showed that the extract at lower concentrations inhibited oxytocin-induced uterine contractions and at higher concentrations, stimulated uterine contraction. This study thus aims to determine, the possible mechanisms by which AET stimulates uterine contraction in vitro. MATERIALS AND METHODS: The contractile effect of AET (5.0 x 10(-2) to 100 x 10(-2)mg/ml) and oxytocin (which was used as a reference drug) were examined in the presence of the following antagonists: atropine (1.18 and 11.91 nM); indomethacin (1.42 and 14.25 nM); verapamil (2.03 and 20.35 nM); phentolamine (4.09 and 40.91 nM), or diphenhydramine (4.45 and 44.47 nM). The EC(50) and E(max) were determined and statistically analyzed using one-way ANOVA and Dunnett post hoc test. RESULTS: There was no significant difference in the EC(50) and E(max) of AET and oxytocin in the presence of atropine. Diphenhydramine and phentolamine significantly inhibited (p<0.01) the extract but both drugs had no effect on oxytocin. However, significant differences (p<0.01) were observed in the EC(50) and E(max) of AET and oxytocin in the presence of verapamil and indomethacin. CONCLUSIONS: These results suggest that the stimulation of uterine contractility by AET may arise from the activation of histamine H(1)- and/or alpha-adrenergic receptors, interference with calcium channels and/or stimulation of prostaglandin synthesis in utero.

Antiinflammatory Activity of Aqueous Extract of Stereospermum kunthianum (Cham, Sandrine Petit) Stem Bark in Rats.

Stereospermum kunthianum, Cham, Sandrine Petit (family: Bignoniaceae) is used in traditional medicine to treat bronchitis, pneumonia and coughs, gastritis, wounds, rheumatic arthritis, ulcers, dysentery, leprosy and venereal diseases in humans. The antiinflammatory activity of the aqueous extract of the stem bark was investigated with experimental animal models using the carrageenan-induced paw oedema, leucocytes migration and granuloma air pouch tests in rats. The extract (100, 200 or 400 mg/kg) at 3 h post-treatment caused a significant (p<0.05) reduction in the paw oedema in rats. The effect of the extract was most pronounced at the dose of 400 mg/kg and was higher than that of indomethacin (10 mg/kg). The extract (400 mg/kg) caused a significant (p<0.05) reduction in the number of recruited leucocytes and it's inhibition of peritoneal exudate formation was comparable to that of indomethacin at a dose of 10 mg/kg. The exudate formation inhibited by 400 mg/kg of the extract in the granuloma air pouch test was comparatively less to that of indomethacin at a dose of 10 mg/kg. The findings of the study indicate that the aqueous extract of Stereospermum kunthianum stem bark possesses antiinflammatory activity which is probably related to the inhibition of prostaglandin synthesis. This is a possible rationale for its folkloric use as an antiinflammatory agent.

Aqueous stem bark extract of Stereospermum kunthianum (Cham, Sandrine Petit) protects against generalized seizures in pentylenetetrazole and electro-convulsive models in rodents.

Stereospermum kunthianum, Cham Sandrine Petit (Bignoniaceae) known in English as pink jacaranda is used in traditional medicine to treat an array of ailments including febrile convulsions in infants and young children by the rural dwellers in Nigeria. This study examined the anticonvulsant activity of its aqueous stem bark extract (100 - 400mg/kg) against maximal electroshock and pentylenetetrazole-induced seizures in rodents. Phenobarbitone and ethosuximide were used as reference anticonvulsant drugs for comparison. Stereospermum kunthianum extract (200 - 400mg/kg, i.p.) remarkably protected (76.9% and 84.6 % respectively) the rats against electroshock-induced seizures. However, the extract (200- 400mg/kg) when administered orally showed a comparatively less effect (33.3% and 55.6% respectively) to the intraperitoneally administered extract in the maximal electroshock test. The extract (100-400mg/kg, i.p.) significantly delayed (p<0.05) the onset of pentylenetetrazole-induced clonic seizures but only slightly prolonged the time of death of the mice. Although the findings in the present study do not provide conclusive evidence, it appears that the aqueous stem bark extract of Stereospermum kunthianum produces its antiseizure effect by enhancing GABAergic neurotransmission and/or action in the brain. The results indicate that the aqueous extract possesses anticonvulsant activity in rodents and therefore tend to suggest that the shrub may be used as a natural supplementary remedy in the management, control and/or treatment of childhood convulsions. It can be concluded that the aqueous stem bark extract possesses anticonvulsant activity and therefore lend pharmacological credence to the traditionally claimed use in the treatment of childhood convulsions.

Aqueous stem bark extract of Stereospermum kunthianum (cham, Sandrine Petit) protects against generalized seizures in pentylenetetrazole and electro-convulsive models in Rodents

Abstract: Stereospermum kunthianum, Cham Sandrine Petit (Bignoniaceae) known in English as pink jacaranda is used in traditional medicine to treat an array of ailments including febrile convulsions in infants and young children by the rural dwellers in Nigeria. This study examined the anticonvulsant activity of its aqueous stem bark extract (100 ­ 400mg/kg) against maximal electroshock and pentylenetetrazole-induced seizures in rodents. Phenobarbitone and ethosuximide were used as reference anticonvulsant drugs for comparison. Stereospermum kunthianum extract (200 ­ 400mg/kg, i.p.) remarkably protected (76.9% and 84.6 % respectively) the rats against electroshock-induced seizures. However, the extract (200- 400mg/kg) when administered orally showed a comparatively less effect (33.3% and 55.6% respectively) to the intraperitoneally administered extract in the maximal electroshock test. The extract (100-400mg/kg, i.p.) significantly delayed (p<0.05) the onset of pentylenetetrazole-induced clonic seizures but only slightly prolonged the time of death of the mice. Although the findings in the present study do not provide conclusive evidence, it appears that the aqueous stem bark extract of Stereospermum kunthianum produces its antiseizure effect by enhancing GABAergic neurotransmission and/or action in the brain. The results indicate that the aqueous extract possesses anticonvulsant activity in rodents and therefore tend to suggest that the shrub may be used as a natural supplementary remedy in the management, control and/or treatment of childhood convulsions. It can be concluded that the aqueous stem bark extract possesses anticonvulsant activity and therefore lend pharmacological credence to the traditionally claimed use in the treatment of childhood convulsions

Aqueous stem bark extract of Stereospermum kunthianum (cham, sandrine petit) protects against generalized seizures in pentylenetetrazole and electro-convulsive models in rodents

Stereospermum kunthianum; Cham Sandrine Petit (Bignoniaceae) known in eng as pink jacaranda is used in traditional medicine to treat an array of ailments including febrile convulsions in infants and young children by the rural dwellers in Nigeria. This study examined the anticonvulsant activity of its aqueous stem bark extract (100 - 400mg/kg) against maximal electroshock and pentylenetetrazole-induced seizures in rodents. Phenobarbitone and ethosuximide were used as reference anticonvulsant drugs for comparison. Stereospermum kunthianum extract (200 - 400mg/kg; i.p.) remarkably protected (76.9and 84.6respectively) the rats against electroshock-induced seizures. However; the extract (200- 400mg/kg) when administered orally showed a comparatively less effect (33.3and 55.6respectively) to the intraperitoneally administered extract in the maximal electroshock test. The extract (100-400mg/kg; i.p.) significantly delayed (p0.05) the onset of pentylenetetrazole-induced clonic seizures but only slightly prolonged the time of death of the mice. Although the findings in the present study do not provide conclusive evidence; it appears that the aqueous stem bark extract of Stereospermum kunthianum produces its antiseizure effect by enhancing GABAergic neurotransmission and/or action in the brain. The results indicate that the aqueous extract possesses anticonvulsant activity in rodents and therefore tend to suggest that the shrub may be used as a natural supplementary remedy in the management; control and/or treatment of childhood convulsions. It can be concluded that the aqueous stem bark extract possesses anticonvulsant activity and therefore lend pharmacological credence to the traditionally claimed use in the treatment of childhood convulsions

Effects of potassium adaptation on blood pressure and pressor responses in normotensive and renal hypertensive Wistar rats.

Potassium adaptation reduces blood pressure (BP) in hypertensive humans and animals but its effects on normotensive BP and the nature of pressor responses to vasoactive drugs are not known. We measured directly, the mean arterial pressure (MAP) of normotensive control, normotensive potassium-adapted (given 0.75% potassium chloride solution for 5 weeks), renal hypertensive (RHP), and renal hypertensive Wistar rats later adapted to potassium. The maximum percentage change, the ED25, and recovery times after bolus injections of noradrenaline (NA), angiotensin II (Ang. II), sodium nitroprusside (SNP), and acetylcholine (ACh) were compared. The MAP of normotensive potassium-adapted rats was significantly lower than that of the normotensive controls (95.6+/-5.0 vs. 110.8+/-2.8 mmHg, p<0.05). The potassium-adapted hypertensive rats (RHP-A) also had significantly lower MAP values than the non-adapted hypertensive ones (116.0+/-4.4 vs. 138.2+/-4.1 mmHg, p<0.01). Potassium adaptation significantly blunted responses to NA and augmented responses to SNP but while the duration of action of Ang. II was significantly shortened, that of SNP was significantly increased. We conclude that potassium adaptation reduces BP in the normotensive and hypertensive rats and may influence both the degree and duration of action of vasoactive drugs given as bolus injections.

Effect of the aqueous extract of Chrysanthellum indicum on calcium mobilization and activation of rat portal vein.

The effects of the aqueous extract of Chrysanthellum indicum (CI) on calcium activation and mobilization were studied using the rat portal vein. The extract caused a concentration-dependent contraction of the portal vein. KCl (80 mM), norepinephrine (NA, 10(-6)M) and CI (4 mg/ml) evoked sustained contraction of the portal vein. In Ca-free medium (with EGTA) the contractions evoked by these agents were reduced significantly. The times-to-peak of KCl, NA and CI were similar -in normal PSS, but in Ca-free medium the times-to-peak for KCl and CI were greatly increased. The contractions induced by CI were not inhibited by chlorpropamide and prazosin, but were blocked by verapamil. The data obtained suggest that the aqueous extract of CI utilizes extracellular calcium pools to bring about contractile response and this effect might be mediated through the activation of potential-sensitive channels.

Haematological influences of potassium adaptation in normotensive and renally-hypertensive Wistar rats.

Dietary potassium is known to cause reduction in blood pressure in several models of hypertension in human and animal studies but its haematological effects are not known. Here, experiments are designed to study the haematological effects of potassium adaptation (achieved by administering 0.75% KCl solution in drinking water for five weeks) in Wistar rats. The animals are divided into four groups comprising controls, potassium-adapted, renal hypertensive, and renal hypertensive with later adaptation to potassium. Packed cell volume (PCV) and platelet count (PC), whole blood and plasma viscosities, and platelet aggregation in the presence of sodium nitroprusside, levcromakalim, and glibenclamide, are studied. Results showed comparable PCV and PC in all groups. While relative whole blood viscosity was significantly higher (P<0.05) in the hypertensive group, relative plasma viscosity was similar in all groups. Adaptation significantly reduced (P<0.05) the tendency of platelets to aggregate to collagen. Sodium nitroprusside significantly reduced (P<0.05) the pro-aggregatory effects of collagen only in the control group. Neither of the potassium-channel modulators (levcromakalim, glibenclamide) caused any significant alteration in platelet response to collagen at the concentrations studied. Although these results suggest that potassium adaptation may not affect haemorheology, the reduced ability of platelets to aggregate--by mechanisms not clearly understood--has implications for reduced thromboembolism and the attendant cardiovascular sequelae.

Some studies on the rodenticidal action of indomethacin.

The oral LD50 of indomethacin for a seven-day observation was found to be 12.58 +/- 1.15 mg/kg. At LD10 of 6.61 mg/kg, a dose to weight ratio of 28 was obtained for a 240 g rat, while at a maximum single dose of 3 mg/kg in man it is only 0.04. Neither diazepam nor phenobarbital influenced death at the doses of both drugs used. However, cholestyramine 2 g/kg/day was found to protect by 50% from the LD100 of indomethacin. Gross pathological studies showed dose-dependent ulceration and perforation (P < 0.001, 12 vs 24 mg/kg) and such lesions occurred in starved rats, were low in bile duct-ligated compared to sham-operated rats (P < 0.001) and were also low in cholestyramine-treated rats. Indomethacin-induced lethality in rats was found to be dose-dependent.

Control of water-borne parasitic diseases with natural products: the potential of Dialium guineense as a molluscicide.

The molluscicidal activity of the fruit and leaves of Dialium guineense was found to be due to glycosides of the triterpenoid oleanolic acid. Three glycosides were isolated from the fruit and a fourth from the leaves and are known compounds. The amount of total saponins present in D. guineense makes it a good candidate for a readily available molluscicide in Nigerian villages.

Occlusion and reperfusion-induced arrhythmias in rats: involvement of platelets and effects of calcium antagonists.

The role of blood platelets in ischemia- and reperfusion-induced arrhythmias and the efficacy of three calcium blocking drugs (verapamil, diltiazem, and nicardipine) in preventing the arrhythmias were investigated. Using anesthetized rats, we measured platelet count (Pc) continuously in vivo with a Technicon autocounter. Thromboxane B2 (TxB2) and 6-keto-PGF1 alpha levels in blood from coronary sinus were determined by radioimmunoassay (RIA). Myocardial ischemia and arrhythmias were monitored from lead I ECG during and after occlusion of the left anterior descending coronary artery (LAD) for 7 min. Ischemia-induced arrhythmias were mainly ventricular ectopic contractions (VECs), whereas reperfusion produced VECs, ventricular tachycardia (VT), and reversible and irreversible ventricular fibrillation (VF). Both ischemia and reperfusion decreased platelet count and increased TxB2 level in blood from the coronary sinus. The effects of the CEBs were determined at two dose levels (0.1 and 0.3 mg/kg). Each calcium entry blocker (CEB), at both dose levels, significantly inhibited ischemia-induced arrhythmias. Verapamil and diltiazem significantly reduced reperfusion-induced VECs, prevented VT and irreversible VF, and reduced the number of animals with reversible VF. Nicardipine in preventing arrhythmias was not very effective at either dose. The CEBs also inhibited both ischemia- and reperfusion-induced decreases in PC with a moderate increase (up to 7%) as compared with levels in sham-operated controls. The CEBs also significantly reduced TxB2 levels in blood from the coronary sinus. These results indicate that ischemia and postischemic reperfusion both induce platelet aggregation in rats. Aggregating platelets release biologically active substances including thromboxane A2 (TxA2) which exacerbates existing ischemia and facilitates generation of arrhythmias. CEBs inhibit platelet aggregation and TxA2 release and enhance PGI2 synthesis, thereby preventing arrhythmias.

Pathological Changes Induced by Chrysobalanus Icaco Seeds

The study was to determine possible pathological changes induced by the consumption of C. icaco and possible health implication. Animal feed tests were carried out using varying amounts of the seed mixed with usual mice meals. The result revealed weight loss; and increase in total bilirubin; protein; albumin; globin; cholesterol level; alkaline phosphate and mean serum glutamic - oxaloacetate transaminase and serum glutamic - pyruvic transaminase activities. Possible health implications are discussed