Renal and Hepatic Function in Hypercholesterolemic Rats Fed Jamaican Bitter Yam (Dioscorea polygonoides).

BACKGROUND: We reported that Jamaican bitter yam (Dioscorea polygonoides) has antilipemic potential in rats; however there is limited data on the toxicological profile of the yam. We therefore investigated the effects of bitter yam consumption for 6 or 12 weeks on renal and hepatic function in rats fed a high (4%) cholesterol diet. METHODS: Twenty four rats were divided into six groups (n = 4); three of which were used for each investigation (6 or 12 weeks). One group was administered 4% cholesterol diet, while the yam group had the cholesterol diet supplemented with 5% bitter yam. The control group was fed standard rat chow. Liver and kidney function tests were performed on serum, liver and kidney. Histological studies were conducted on liver samples. Acute toxicity tests were performed in rats and mice administered a single high dose of bitter yam (10 g/kg). RESULTS: Activities of liver and kidney AST and ALT differed (p ≤ .02) between control rats and those fed cholesterol with bitter yam for 12 weeks. Albumin to globulin ratio was reduced (p = .03) in rats fed cholesterol with bitter yam for 6 weeks as compared to the control group. Serum urea concentration was higher (p < .05) in rats fed bitter yam as compared to normal chow for 6 weeks. The cholesterol diet caused extensive fat deposition in liver cells; however this was inhibited by co-administration of bitter yam. CONCLUSION: Long-term administration of Jamaican bitter yam may induce slight changes in renal and hepatic functions.

Effects of Jamaican bitter yam (Dioscorea polygonoides) and diosgenin on blood and fecal cholesterol in rats.

A sapogenin-rich preparation from Jamaican bitter yam (Dioscorea polygonoides) has been shown to reduce blood cholesterol concentrations in hypercholesterolemic rats and mice. Also, diosgenin supplementation has been reported to have antilipemic effects in several animal species. We investigated potential mechanisms of the lipid-lowering actions of bitter yam and also whether the actions were mediated by diosgenin. Sprague-Dawley rats were fed a hypercholesterolemic diet (4% cholesterol) alone or with 5% bitter yam or 1% diosgenin supplementation for 6 weeks. The control group was fed normal rat chow. The serum lipid profile, fecal cholesterol concentration, and serum lipase activity were assessed at the end of the period. The induction of hypercholesterolemia was inhibited by coadministration of 5% bitter yam or 1% diosgenin in the diet. Serum lipid profiles were similar in rats fed bitter yam or diosgenin. The fecal cholesterol concentration was significantly (P < .01) higher in rats fed diosgenin compared to the cholesterol group. However, there was no corresponding elevation in the group fed bitter yam. Administration of bitter yam or diosgenin supplement significantly increased (P < .01) the serum lipase activity compared to the normal control and cholesterol groups. The cholesterol-supplemented diet inhibited normal gain in body weight over the period. This action was potentiated by diosgenin. The effects of the respective supplements on body weight were not completely explained by food consumption. Supplementation of the diet with Jamaican bitter yam may be therapeutically beneficial in the management of hypercholesterolemia.

6-Shogaol reduced chronic inflammatory response in the knees of rats treated with complete Freund's adjuvant.

BACKGROUND: 6-Shogaol is one of the major compounds in the ginger rhizome that may contribute to its anti-inflammatory properties. Confirmation of this contribution was sought in this study in Sprague- Dawley rats (200-250 g) treated with a single injection (0.5 ml of 1 mg/ml) of a commercial preparation of complete Freund's Adjuvant (CFA) to induce monoarthritis in the right knee over a period of 28 days. During this development of arthritis, each rat received a daily oral dose of either peanut oil (0.2 ml-control) or 6-shogaol (6.2 mg/Kg in 0.2 ml peanut oil). RESULTS: Within 2 days of CFA injection, the control group produced maximum edematous swelling of the knee that was sustained up to the end of the investigation period. But, in the 6-shogaol treated group, significantly lower magnitudes of unsustained swelling of the knees (from 5.1 +/- 0.2 mm to 1.0 +/- 0.2 mm, p < 0.002, n = 6) were produced during the investigation period. Unsustained swelling of the knees (from 3.2 +/- 0.6 mm to 0.8 +/- 1.1 mm, p < 0.00008, n = 6) was also produced after 3 days of treatment with indomethacin (2 mg/Kg/day) as a standard anti-inflammatory drug, but during the first 2 days of drug treatment swelling of the knees was significantly larger (11.6 +/- 2.0 mm, p < 0.0002, n = 6) than either the controls or the 6-shogaol treated group of rats. This exaggerated effect in the early stage of indomethacin treatment was inhibited by montelukast, a cysteinyl leukotriene receptor antagonist. Also, 6-shogaol and indomethacin were most effective in reducing swelling of the knees on day 28 when the controls still had maximum swelling. The effect of 6-shogaol compared to the controls was associated with significantly lower concentration of soluble vascular cell adhesion molecule-1 (VCAM-1) in the blood and infiltration of leukocytes, including lymphocytes and monocytes/macrophages, into the synovial cavity of the knee. There was also preservation of the morphological integrity of the cartilage lining the femur compared to damage to this tissue in the peanut oil treated control group of rats. CONCLUSION: From these results, it is concluded that 6-shogaol reduced the inflammatory response and protected the femoral cartilage from damage produced in a CFA monoarthritic model of the knee joint of rats.

The characterization of the activity of a bark extract from Fagara martinicensis on the rat vas deferens

OBJECTIVE: An aqueous extract made from the bark of Fagara martinicensis (family Rutaceae) was examined for its effect on the isolated rat vas deferens. METHOD: The investigation involved measurement of isometric tension in the prostatic and epididymal portions of the isolated rat vas deferens which was anchored in an organ bath with physiological solution. Non-cumulative doses of Fagara martinicensis (FM) were added to the bath and the effects examined in the presence of receptor antagonists to characterize the actions of FM. Results before and after antagonist additions were compared. RESULTS: Non-cumulative addition of FM (1.6 mg/ml to 14.1 mg/ml) produced contractions of both portions of the vas deferens, with the epididymal portion showing greater sensitivity to the effects of FM. The contractions consisted of a rhythmic component superimposed on a phasic and tonic component. All components of the contractions were abolished by prazosin (2.1 uM), a selective a1-adrenoreceptor antagonist, and therefore it was concluded that FM contractions are due to agonist activities on these receptors. Since stimulation of a1-adrenoreceptora results in the mobilization of extracellular calcium into the muscle, the involvement of extracellular calcium was investigated with calcium channel antagonist, nifedipine (0.11-6.0 uM). Nifedipine inhibited all components of the contraction. This effect indicates that entry of extracellular calcium into the muscle was involved in all components of the contraction and further confirms a1-adrenoreceptor agonist action of Fagara martinicensis. CONCLUSIONS: Fagara martinicensis may therefore be a potential source of drugs with a1-adrenoreceptor agonist properties. (AU)

Investigation of the anti-inflammatory properties of leaves of Artocarpus altilis (breadfruit)

OBJECTIVE: The leaves of the breadfruit tree (Artocarpus altilis) are used in folklore medicine in the Caribbean to relieve pain and inflammmation. Our objective was to determine whether there is any scientific basis to this folkloric claim. METHODS: An aqueous decoction of breadfruit leaves (BL) was prepared, and tested for anti-inflammatory activity using the "carrageenan induced rat paw oedema" method. Groups of rats were given doses of BL (15, 30 and 60 mg/kg) and saline (control). Additional experiments were done on isolated guinea pig trachea challenged with acetylcholine (Ach), prostaglandin E2 (PGE2), bradykinin and histamine to investigate the mechanism of action of BL. RESULTS: BL at a dose of 60 mg/kg exhibited significant anti-inflammatory activity (p<0.05) from 0.5 to 4 hours. Lower doses of BL (15 and 30 mg/kg) did not produce any significantly different effects from control (p>0.05). BL antagonized the actions of PGE2 and bradykinin on the trachea but not that of Ach or histamine. CONCLUSION: Our findings suggests that an extract of the breadfruit leaves contains one or more compounds with significant anti-inflammatory properties. However, further studies are required to isolate these compounds and to determine their pharmacological profile. (AU)

Evidence that guanylate cyclase is involved in modulating the resting tension and neurally induced contraction of the guinea pig tracheal muscle

Electrical field stimulation of guinea-pig tracheal muscle strips produced a frequency-dependent biphasic response consisting of an initial cholinergic contraction followed by relaxation. Both phases of the response were of neural origin. In the presence of methylene blue, a guanylate cyclase inhibitor, the resting tension and the contraction were increased, but the accompanying relaxation was inhibited. However, in the presence of sodium nitroprusside, guanylate cyclase activator, the resting tension was reduced and the contraction was inhibited, but the relaxation was prolonged and increased. Similarly, in the presence of either 3-isobutyl-lmethylxanthine, which promotes cyclic guanosine monophospate (cGMP) accumulation, or 8-bromo-cGMP, an analogue of cGMP, the resting tension was reduced and the contraction was inhibited but the relaxation was prolonged and increased. From these results, it is concluded that guanylate cyclase is involved in modulating the resting tension and the neurally-induced contraction of guinea-pig tracheal muscle

Evidence that guanylate cyclase is involved in modulating the resting tension and neurally induced contraction of the guinea pig tracheal muscle

Electrical field stimulation of guinea-pig tracheal muscle strips produced a frequency-dependent biphasic response consisting of an initial cholinergic contraction followed by relaxation. Both phases of the response were of neural origin. In the presence of methylene blue, a guanylate cyclase inhibitor, the resting tension and the contraction were increased, but the accompanying relaxation was inhibited. However, in the presence of sodium nitroprusside, guanylate cyclase activator, the resting tension was reduced and the contraction was inhibited, but the relaxation was prolonged and increased. Similarly, in the presence of either 3-isobutyl-lmethylxanthine, which promotes cyclic guanosine monophospate (cGMP) accumulation, or 8-bromo-cGMP, an analogue of cGMP, the resting tension was reduced and the contraction was inhibited but the relaxation was prolonged and increased. From these results, it is concluded that guanylate cyclase is involved in modulating the resting tension and the neurally-induced contraction of guinea-pig tracheal muscle(AU)

Streptozotocin alters pancreatic beta-cell responsiveness to glucose within six hours of injection into rats

A 24-hour glycaemic profile following streptozotocin (80 mg/kg. ip) injection was investigated in fasted rats. The most prominent changes in blood glucose were hyperglycaemia associated with low levels of plasma insulin after two hours followed by hypoglycaemia associated with high levels of plasma insulin after six hours; subsequently hyperglycaemia progressively developed and this was associated with decreasing levels of plasma insulin. Further probing revealed that at two hours after streptozotocin injection, the pancreatic ß-cells could not respond to an oral glucose load while, at six hours after, there was an apparent return of ß-cell responsiveness, but subsequently ß-cell responsiveness was progressively lost and histological examination revealed cellular damage. From these results, it is concluded that within six hours of injection, stretozotocin initiates pancreatic ß-cell damage which leads to the development of diabetes mellitus.

Streptozotocin alters pancreatic beta-cell responsiveness to glucose within six hours of injection into rats

A 24-hour glycaemic profile following streptozotocin (80 mg/kg. ip) injection was investigated in fasted rats. The most prominent changes in blood glucose were hyperglycaemia associated with low levels of plasma insulin after two hours followed by hypoglycaemia associated with high levels of plasma insulin after six hours; subsequently hyperglycaemia progressively developed and this was associated with decreasing levels of plasma insulin. Further probing revealed that at two hours after streptozotocin injection, the pancreatic á-cells could not respond to an oral glucose load while, at six hours after, there was an apparent return of á-cell responsiveness, but subsequently á-cell responsiveness was progressively lost and histological examination revealed cellular damage. From these results, it is concluded that within six hours of injection, stretozotocin initiates pancreatic á-cell damage which leads to the development of diabetes mellitus. (AU)

Activation of guanylate cyclase in the guinea-pig trachea reduces contractile responses of the smooth muscle

Guinea-pig tracheal strips were used to investigate whether activation of guanylate cyclase in the trachea can reduce the contractile response of the smooth muscle. Guanylate cyclase was activated by glyceryl trinitrate and a combination of sodium nitrite and ascorbic acid. These activators inhibited tracheal smooth muscle contractions produced by acetylcholine histamine and electrical field stimulation. However, in the presence of methylene blue, a guanylate cyclase inhibitor, tracheal smooth muscle contractions were not inhibited by the activators. But, in the presence of propranolol, which blocked inhibition mediated by beta-adrenoceptor, both glyceryl trinitrate and the sodium nitrite/ascorbic acid combination were still capable of inhibiting tracheal smooth muscle contractions. Additionally, methylene blue inhibited tracheal smooth muscle relaxation that was electrically induced. These results suggest that the inhibitory action mediated by activated guanylate cyclase may be a mechanism for regulating tracheal smooth muscle contractile reponses

Activation of guanylate cyclase in the guinea-pig trachea reduces contractile responses of the smooth muscle

Guinea-pig tracheal strips were used to investigate whether activation of guanylate cyclase in the trachea can reduce the contractile response of the smooth muscle. Guanylate cyclase was activated by glyceryl trinitrate and a combination of sodium nitrite and ascorbic acid. These activators inhibited tracheal smooth muscle contractions produced by acetylcholine histamine and electrical field stimulation. However, in the presence of methylene blue, a guanylate cyclase inhibitor, tracheal smooth muscle contractions were not inhibited by the activators. But, in the presence of propranolol, which blocked inhibition mediated by beta-adrenoceptor, both glyceryl trinitrate and the sodium nitrite/ascorbic acid combination were still capable of inhibiting tracheal smooth muscle contractions. Additionally, methylene blue inhibited tracheal smooth muscle relaxation that was electrically induced. These results suggest that the inhibitory action mediated by activated guanylate cyclase may be a mechanism for regulating tracheal smooth muscle contractile reponses (AU)

Demonstration of bioequivalence between ventasol syrup and ventolin syrup in humans and in dogs

Ventasol syrup, a new locally produced salbutamol formulation, was compared with the standard salbutamol formulation, ventolin syrup, for determination of oral bioequivalence in stable asthmatic human subjects and in dogs. On separate occasions, each subject received a single 10 ml oral dose of each formulation containing 4 mg salbutamol. In the human subjects, statistically similar peak plasma concentrations of salbutamol were obtained (196ñ7ng/ml for ventasol syrup and 185ñ6ng/ml for ventolin syrup) 3 hours after oral administration of the formulations. From the ratio of the AUC 0-ý for the formulations (1.04), a relative oral bioavailability of 104 per cent , indicating equivalent total salbutamol output, was also obtained in the human subjects. Similarly, in the dogs, the formulations produced statistically equivalent peak plasma concentrations of salbutamol (259ñ24ng/ml for ventasol syrup and 285ñ29ng/ml for ventolin syrup) 3 hours after oral administration. Also, from the ratio of AUC 0-ý for the formulation (1.02), a relative oral bioavailability of 102 per cent , indicating similar total salbutamol output, was obtained in the dogs. From these results, it is concluded that oral bioequivolence between ventasol syrup and ventolin syrup was demonstrated in human subjects and in dogs.

Demonstration of bioequivalence between ventasol syrup and ventolin syrup in humans and in dogs

Ventasol syrup, a new locally produced salbutamol formulation, was compared with the standard salbutamol formulation, ventolin syrup, for determination of oral bioequivalence in stable asthmatic human subjects and in dogs. On separate occasions, each subject received a single 10 ml oral dose of each formulation containing 4 mg salbutamol. In the human subjects, statistically similar peak plasma concentrations of salbutamol were obtained (196ñ7ng/ml for ventasol syrup and 185ñ6ng/ml for ventolin syrup) 3 hours after oral administration of the formulations. From the ratio of the AUC 0-y for the formulations (1.04), a relative oral bioavailability of 104 percent, indicating equivalent total salbutamol output, was also obtained in the human subjects. Similarly, in the dogs, the formulations produced statistically equivalent peak plasma concentrations of salbutamol (259ñ24ng/ml for ventasol syrup and 285ñ29ng/ml for ventolin syrup) 3 hours after oral administration. Also, from the ratio of AUC 0-y for the formulation (1.02), a relative oral bioavailability of 102 percent, indicating similar total salbutamol output, was obtained in the dogs. From these results, it is concluded that oral bioequivolence between ventasol syrup and ventolin syrup was demonstrated in human subjects and in dogs. (AU)

Unstable diabetic state produced by a small dose of streptozotocin in rats

A diabetic state was induced with a single intraperitoneal dose (45 mg/kg) of streptozotocin in rats. Their fasting blood glucose concentrations oscillated between 12.7 ñ 1.9 mmol/l and 4.6 ñ 0.6 mmol/l during 35 days of monitoring. Their body weights were also reduced, while controls gained weight, although food consumption was not significantly different. Also, within the first «-hour of the oral glucose tolerance test, blood glucose concentration increased in the diabetic and the control rats, but only in the control rats was there a simultaneous increase in serus IRI concentration (7.2 ñ 8 x 10 to the 2nd power pmol/l to 27.0 ñ 5.2 x 10 to the 2nd power pmol/l) which, like the blood glucose concentration, subsequently fell to fasting level in the control rats. In the diabetic rats, however, it was not until the following hour of the tolerance test that serum IRI concentration increased (3.4 ñ 0.3 x 10 to the 2nd power pmol/l to 65.0 ñ 12.5 x 10 to the 2nd power pmol/l) and blood glucose concentration began to fall. By the end of the test in the diabetic rats, blood glucose concentration fell but remained significantly higher than the control value. Additionally, no pancreatic tumours were identified in these diabetic rats. The results therefore suggest that an unstable diabetic state was produced by streptozotocin because the treshold for insulin secretion by glucose was increased, while the production of insulin by the pancreas was not significantly affected (AU)

Supporting evidence for the use of cassava (manihot esculeta) products instead of wheat flour products in the diet of the diabetic

The extent of blood glucose increases produced by products of cassava and wheat flour were compared in experiments performed in cats and rats. In normal anaesthetized cats, a meal of 500 mg grated cassava preparation produced a mean maximum blood glucose increase which is 200 percent less than the mean maximum blood glucose increase produced by a meal of 500 mg wheat flour preparation. In diabetic rats, a 20 gm homogenous mixture, consisting of 50 percent cassava bammmy and 50 percent rat chow that was eaten within a 24-hour period, produced a mean blood glucose increase which is 221 percent less than the blood glucose increase produced by a 20gm homogenous mixture, consisting of 50 percent wheat flour bread and 50 percent rat chow and eaten over a similar period of time. The lower glycaemic reponses of the cassava preparations therefore represent significant advantages over wheat flour preparations, for its (cassava preparation) inclusion in the diet of the diabetic (AU)

Demonstration of anticonvulsant properties of an aqueous extract of Spirit Weed (Eryngium foetifdum L.)

Rats were used to investigate the anticonvulsant potential of two aqueous extracts of Spirit Weed. In this investigation, convulsions were induced by picrotoxin (4.5 mg/kg, i.p.) and these convulsions were consistently abolished by the intraperitioneal (i.p.) infections of aliquots (3ml each) of a steam distillate extract of Spirit Weed. However, those rats which served as controls as well as those which were injected with aliquots (3 ml each) of the boiled aqueous decoction of Spirit Weed, died after 2 hours of convulsions. Also, the steam distillate extract of Spirit Weed delayed (by 12 + 3 minutes) the onset of convulsions when it was given before picrotoxin (4.5 mg/kg, i.p.). Additionally, the steam distillate extract of Spirit Weed mimicked the anticonvulsant effect of phenobarbitone in the same group of rats. Moreover, the steam distillate extract of Spirit Weed did not produce generalized central nervous sustem depression in conscious rats. Therefore, it is concluded that an ingredient in the steam distillate extract of Spirit Weed has anticonvulsant properties which may be useful in the treatment of some forms of epilepsy. This requires further investigation (AU)

Caffeine inhibits the central hypotensive action of propranolol in rats

Rats anaesthetized with alpha-chloralose were used to investigate the effects of caffeine on the central hypotensive action of d, l-propranolol(=propranolol). In these rats, intracisternal injections of graded doses (1.7 pmol to 13.6 pmol) of propranolol produced dose-dependent falls in mean arterial blood pressure (7 ñ 0.6 mm Hg to 27 ñ 2 mm Hg) which were inhibit by pretreatment with caffeine at a dose (12.9 pmol, intracisternally) that did not alter basal mean arterial blood pressure. The inhibition was reversible and it had an onset and duration of action of about 10 and 50 minutes respectively. It is concluded that caffeine may reduce the hypotensive response of propranolol during antihypertensive therapy with this drug (AU)

Blood pressure responses to stimulation of afferent fibres in the renal nerve of the rat

Chloralose-anesthetised rats were to investigate the blood pressure (BP) responses to electrical stimulation of afferent fibres in the renal nerve. In these rats, stimulation of the proximal end of the cut renal nerve produced either a rapidly reversed fall in BP (at 3V, 5V and 10V) or an initial fall followed by a rise in BP (at 5V and 10V). Dissection of the nerve into two branches and subsequent stimulation yielded a fall in BP by one branch and a rise by the other branch. Also, stimulation of the renal nerve before and after transection at various levels of the medulla oblongata and the spinal cord produced results which indicated that the fall in BP was a bulbar reflex that was integrated at the obex in the medulary region of the brain, but the rise in BP was a spinal reflex that was integrated at a spinal site caudal to the second cervical segment. It is concluded that,in the rat, there are at least two distinct groups of renal afferent fibres which can mediate blood pressures changes that may represent important renal regulatory reflexes.(AU)