Displaying all 12 publications

Abstract:
Sort:
  1. Ruszymah BH, Nabishah BM, Aminuddin S, Sarjit S, Khalid BA
    Malays J Pathol, 1999 Jun;21(1):51-8.
    PMID: 10879279
    Corticotrophin releasing factor (CRF) and beta-endorphin (beta EP) containing neurons are shown to be present in the hypothalamus and both neurons are found at the paraventricular nucleus (PVN). Steroid hormones have been found to alter the plasma level of these neurotransmitters. Glycyrrhizic acid (GCA) is the active component of liquorice. GCA inhibits the enzyme 11 beta-hydroxysteroid dehydrogenase (11HSD) which is needed for the inactivation of the steroid pathway, so therefore would cause changes to these neurons. The aim of this study was to investigate the effects of GCA as well as deoxycorticosterone (DOC) and dexamethasone (DM) on the modulation of CRF and beta EP containing neuron at the PVN of the hypothalamus. Rats were given either DM, DOC or GCA and adrenalectomized (ADX) and given either DM or DOC. At the end of treatment rats were transfused transcardially before sacrifice and the brain were dissected for immunohistochemical analysis. We found that immunostaining of the CRF containing neurons demonstrate a reduction in the number of positive neurons in DM treated rats. DOC and GCA treated rats showed the same result as in DM rats but the reduction is less. ADX, DM, DOC and GCA treated rats did not show any changes in the number of beta EP containing neurons but naloxone increased the number of beta EP containing neurons markedly. In conclusion, GCA and DOC have similar effects on CRF and beta EP containing neurons at the PVN.
  2. Ainsah O, Nabishah BM, Osman CB, Khalid BA
    PMID: 10595599
    Normal rats, on being repetitively stressed by being restrained in a tight container for two hours, had higher levels of plasma corticosterone compared to pre stress values. These rats also reacted to the stress by a behavioral response in which there was marked decrease in locomotor activity assessed by the open field test (pre stress: 71.3 +/- 2.6 squares crossed versus post stress: 14.3 +/- 2.5 squares crossed) by counting the number of squares entered by the rat over 5 minutes. By the 6th to 7th exposures to the repetitive stress, the rats adapted to the stress and had normal plasma corticosterone levels and locomotor activity scores comparable to the pre stress values. These responses to stress were completely blocked by the administration of 0.32 microg/100 g BW of naloxone i.p at 10 minutes prior to the stress. In rats fed with rat chow supplemented with 90 mg/kg rat chow or 150 mg/kg rat chow of vitamin E, there was significant reduction of the plasma corticosterone levels and improvement in the locomotor activity. Stress thus caused opioid mediated increase in plasma corticosterone and reduction in locomotor activity which could be blocked by naloxone. These stress responses probably also involved generation of oxygen free radicals which were scavenged by the vitamin E, thus reducing the effects of repetitive stress on locomotor activity and serum corticosterone levels.
  3. Nabishah BM, Khalid BA, Morat PB, Zanariyah A
    Exp. Clin. Endocrinol. Diabetes, 1998;106(5):419-24.
    PMID: 9831309
    This study tested the possibility of adrenal autotransplantation in rats. Since the cortex and the medulla of the adrenal gland were from different origin embryologically, either whole adrenal glands (ADR), or capsule and cortex (CAP) or medulla (MED) were autotransplanted in the subcutaneous tissue. The functions of regenerated adrenal nodules were tested by measuring plasma corticosterone levels every fortnight. At the end of 9 weeks the rats were exposed to hypovolemic shock followed by naloxone injection to reverse the shock response. Results showed that rats transplanted with either cortex or whole adrenal started secreting corticosterone at 5 weeks post-transplantation (107.73 +/- 21.98 ng/ml, 126.04 +/- 48.41 ng/ml, respectively). Corticosterone levels increased to the value which were not significantly different from control by 9 weeks post-transplantation. However, rats transplanted with adrenal medulla showed very low corticosterone levels. Nine weeks post-transplantation, the mean blood pressure (MBP) of the CAP group was 135 +/- 13 mmHg and was not significantly different from sham-operated controls, whereas MBP of MED group was significantly lower than sham-operated animals (99 +/- 11 mmHg versus 141 +/- 9 mmHg). The MBP of the ADR group was also lower compared to sham-operated controls (112 +/- 17 mmHg P < 0.05). The MBP of the adrenal group was not statistically significant compared to the CAP group. After 1% body weight haemorrhage, the MBP decreased significantly in ADR (45 +/- 5 mmHg, P < 0.05) and MED group (36 +/- 9 mmHg, P < 0.001) compared to sham-operated rats (78 +/- 11 mmHg) but not in the CAP (56 +/- 9 mmHg). It was concluded that autotransplanted whole adrenal or adrenocortical tissues survived subcutaneously and produced sufficient corticosterone to alleviate haemorrhagic shock. Adrenal medullary tissue failed to regenerate subcutaneously and the presence of adrenal medullary tissue may suppressed the growth of transplanted adrenal gland.
  4. Nabishah BM, Morat PB, Kadir BA, Khalid BA
    Gen. Pharmacol., 1991;22(2):389-92.
    PMID: 1647349
    1. Glucocorticosteroid may relieve bronchospasm by mediating changes in the muscarinic receptor concentration and/or its affinity. 2. Cholinergic muscarinic receptors were determined by using Scatchard's plots from radioligand binding assays of 0.13-3.2 nM [3H]quinuclidinyl benzylate binding to the membrane fraction of bronchial smooth muscle (BSM). 3. The concentration of muscarinic receptor in BSM of normal rat was 57 +/- 3 fmol mg protein and the dissociation constant was 0.07 +/- 0.02 nM. Dexamethasone and corticosterone reduced muscarinic receptor concentration to 50-60% of basal with no changes in receptor affinity. No changes were found in rat treated with deoxycorticosterone. 4. These findings suggest that glucocorticoids but not mineralocorticoid relieve bronchospasm at least partly by reducing the cholinergic hypersensitivity.
  5. Nabishah BM, Merican Z, Morat PB, Alias AK, Khalid BA
    Gen. Pharmacol., 1990;21(6):935-8.
    PMID: 2177714
    1. Steroid hormones have been shown to regulate the concentration of adrenergic and muscarinic receptors in many tissues. 2. The cyclic adenosine 3',5'-monophosphate (cAMP) content in rat lung tissues in response to either dexamethasone, corticosterone, deoxycorticosterone or progesterone for 7 days were measured following intraperitoneal injection of isoprenaline just before sacrificed. 3. There was a significant increase in cAMP level (P less than 0.001) in dexamethasone and corticosterone-treated rats compared to controls that received isoprenaline alone. 4. Pretreatment with deoxycorticosterone and progesterone suppressed the increase in cAMP in response to isoprenaline. 5. The effect of glucocorticoids in causing bronchodilatation in asthmatic patients is partly due to the restoration of adenyl cyclase responsiveness to beta-agonist.
  6. Nabishah BM, Morat PB, Khalid BA, Kadir BA
    Clin Exp Pharmacol Physiol, 1990 Dec;17(12):841-7.
    PMID: 2092952
    1. The effects of corticosteroid pretreatment on acetylcholine (ACH)-induced contraction of bronchial smooth muscle (BSM) were studied. 2. ACH dose-response curves for dexamethasone (DM)- and corticosterone (B)-treated but not deoxycorticosterone (DOC)-treated BSM were significantly shifted to the right; this provides evidence that glucocorticoid treatment reduced the sensitivity of BSM to ACH. 3. Morphine enhanced BSM contraction in response to ACH by 20%. DM suppressed this enhancement. 4. These findings correlated well with the reduction of muscarinic receptor numbers in BSM by glucocorticoids in our previous study. In addition, glucocorticoids reduced the sensitivity of BSM to opioids.
  7. Ainsah O, Nabishah BM, Osman CB, Khalid BA
    Clin Exp Pharmacol Physiol, 1999 7 1;26(5-6):444-8.
    PMID: 10386236
    1. This study was carried out to determine the effect of short-term and long-term ingestion of glycyrrhizic acid on the response to 2 h of restraint stress by measuring locomotor activity and plasma corticosterone levels. 2. Male Sprague-Dawley rats were randomly assigned into four groups, each group having eight rats. Group 1 (control) was given ordinary tap water, while groups 2 (short term), 3 and 4 (both long term) were given tap water containing 1 mg/mL glycyrrhizic acid to drink for 10 days, 4 weeks and 9 weeks, respectively. All the rats were subjected to 2 h of restraint stress and the locomotor activity assessed using an activity test in an open field arena followed by blood sampling to determine the plasma corticosterone level. These procedures were repeated daily for 14 days. 3. The basal locomotor activity scores for rats given glycyrrhizic acid for 10 days or 4 weeks were similar to those of controls; however, that of the rats treated long term with glycyrrhizic acid was significantly lower (21.0 +/- 3.0 squares crossed; P < 0.0005). Following the first period of restraint stress there was a highly significant decrease in locomotor activity, which remained significantly lower until the seventh and subsequent periods, indicating an adaptation to the repeated stress had occurred. Although the decrease in locomotor activity was partially blocked and adaptation to repetitive stress was enhanced in the rats given glycyrrhizic acid for 10 days, this was not seen in rats treated with glycyrrhizic acid for 4 or 9 weeks. The corticosterone levels in control rats were significantly elevated for 4-5 days following the exposure to repetitive stress but decreased gradually from day 7 onwards. However, both short- and long-term glycyrrhizic acid-treated rats had higher plasma corticosterone levels than the controls (P < 0.05). 4. In conclusion, repetitive restraint stress caused decreased locomotor activity associated with increased plasma corticosterone levels, both of which, in normal rats, decreased with adaptation to stress. The stress response was partially blocked and adaptation enhanced in rats given glycyrrhizic acid for 10 days, but not in rats given glycyrrhizic acid for 4 and 9 weeks. Glycyrrhizic acid ingestion caused high plasma corticosterone.
  8. Ainsah O, Nabishah BM, Osman CB, Khalid BA
    Clin Exp Pharmacol Physiol, 1999 7 1;26(5-6):433-7.
    PMID: 10386234
    1. The present study examined the effect of naloxone (NAL), glycyrrhizic acid (GCA), deoxycorticosterone (DOC) and dexamethasone (DEX) on daily repeated 2 h chronic restrained stress (RS) on the locomotor activity (LA) of rats tested in the open field arena to elucidate the possible roles of opioids, glucocorticoids and mineralocorticoids in response to stress. 2. Intact and adrenalectomized (ADX) rats were either injected with 0.1 mL of NAL (0.32 microgram/100 g BW), 2.4 mg/kg DOC or 120 micrograms/kg DEX or had 1.0 mg/mL GCA dissolved in their drinking water or normal saline (for the ADX group) dissolved in their drinking water. 3. In intact groups, treatment with NAL completely blocked the stress response and treatment with GCA, DOC and DEX partially prevented the stress response. Adaptation occurred on either days 4, 5, 6 or 7 for intact rats treated with DEX, DOC, GCA or control rats, respectively. All ADX control rats died following the first 2 h RS. Adrenalectomized rats treated with DEX or DOC adapted later compared with intact rats, while rats given either GCA or NAL were unable to block or adapt to chronic RS. 4. These findings demonstrate that the stress response is primarily mediated by endogenous opioids, in that it is blocked by NAL. Both mineralocorticoids and glucocorticoids, which can act centrally to inhibit endorphins, partially blocked the stress response. The effect of GCA in intact rats was similar to that of both DEX and DOC in intact rats. Adrenalectomized rats treated with GCA (despite their lack of endogenous corticosterone) showed a stress response that was significantly different from the other ADX groups, implying that GCA had effects independent of endogenous corticosterone.
  9. Ruszymah BH, Nabishah BM, Aminuddin S, Khalid BA
    Clin Exp Pharmacol Physiol, 1995 Jan;22(1):35-9.
    PMID: 7768032
    1. The aim of this study was to investigate the effect of repeated exposure to stress on tail blood pressure (TBP) of normal as well as GCA (glycyrrhizic acid) and steroid treated rats. Male Sprague-Dawley rats (250 g) were exposed to ether vapour to achieve light anaesthesia prior to TBP recording. Rats were injected with either normal saline or naloxone prior to exposure to stress. Tail blood pressure was recorded daily for 2 weeks. 2. We found that ether stress caused a transient drop in TBP in control as well as in dexamethasone (DEX) treated rats. The stress-induced fall in blood pressure was reduced by naloxone in control rats but not in DEX treated rats. However the transient drop in TBP following stress was not seen in either GCA or deoxycorticosterone (DOC) treated rats. 3. We conclude that first, the reduction in TBP was due to the release of endogenous opioids caused by stress. Second, DOC may block the release of such endogenous opioids, preventing the drop in TBP in response to stress, while DEX did not. Third, GCA caused a similar mineralocorticoid effect on reversing stress induced hypotension.
  10. Ruszymah BH, Nabishah BM, Aminuddin S, Khalid BA
    Clin Exp Hypertens, 1995 Apr;17(3):575-91.
    PMID: 7613529
    Glycyrrhizic acid (GCA) the active component of liquorice acts by inhibiting 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) which catalyses the reversible conversion of cortisol to cortisone. The aim of this study was to examine the effect of GCA on pulmonary arterial pressure. Male Sprague-Dawley rats (200g) received drinking water containing 0.1 mg/ml and 1.0 mg/ml GCA for 12 weeks. Tail blood pressure (BP) was recorded every three weeks and serum Na+ and K+ were measured at the beginning and the end of the experiment. Right atrial pressure (RAP) were measured at the end of 12 weeks just before the animals were sacrificed. Lung tissues were taken for histological examination using the elastic-van Gieson (EVG) staining method. There was a significant increase in tail BP in GCA treated rats compared to controls, for both dosages used. This was associated with an increase in serum Na+ and a decrease in K+ level. The mean RAP increased significantly from 2.69 +/- 0.23 mmHg to 4.47 +/- 0.32 mmHg (P < 0.001) in 0.1 mg/ml GCA treated rats and 6.86 +/- 0.54 mmHg (P < 0.0001) in rats receiving 1.0 mg/ml GCA in their drinking water. Histological examination showed increased thickness of pulmonary arterial wall (P < 0.0001). In conclusion GCA caused an increase in right atrial pressure as well as thickening of the pulmonary vessels suggesting pulmonary hypertension.
  11. Nabishah BM, Khalid BA, Morat PB, Alias AK, Zainuddin M
    J Endocrinol, 1992 Jul;134(1):73-6.
    PMID: 1323640
    The possible role of cyclic adenosine 3',5'-monophosphate (cAMP) in mediating the action of steroid hormones was investigated using the rat lung. Male rats were adrenalectomized and treated with olive oil, dexamethasone, corticosterone, deoxycorticosterone (DOC) or progesterone. At the end of 10 days, 100 micrograms isoprenaline/kg was injected intraperitoneally 5 min before the animals were killed to stimulate cAMP production. Adrenalectomy significantly decreased cAMP levels in the rat lung. Dexamethasone and corticosterone pretreatment reversed the effect of adrenalectomy whereas progesterone pretreatment but not DOC pretreatment significantly decreased lung cAMP levels. Cyclic AMP levels in normal female rats, whether pregnant or not, were not significantly different from those in male rats. We concluded that the absence of glucocorticoid, as after adrenalectomy, decreased the cAMP levels in rat lungs and that this could be reversed by either dexamethasone or corticosterone replacement. Progesterone reduced the cAMP content in rat lungs by acting as a glucocorticoid antagonist or by acting directly via progesterone receptors.
  12. Nabishah BM, Morat PB, Alias AK, Kadir BA, Khalid BA
    Clin Exp Pharmacol Physiol, 1992 Dec;19(12):839-42.
    PMID: 1335381
    1. Male Sprague-Dawley rats were made either hyper- or hypothyroid with thyroxine or 4-methyl-2-thiouracil, respectively. Bronchial smooth muscle (BSM) contractility and lung cyclic adenosine 3',5'-monophosphate (cAMP) content were measured in both conditions. 2. Bronchial smooth muscle contractility was significantly weaker in hyperthyroid rats, while the BSM contractility of hypothyroid rats was the same as controls. 3. The cAMP content of hyperthyroid rat lungs was similar to controls but was decreased in hypothyroid rats. 4. These studies demonstrated that both the hyper- and hypothyroid states affect respiration, although the mechanisms involved with different for each condition.
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links