el-Sayed Mg

Thymoquinone suppresses expression of inducible nitric oxide synthase in rat macrophages

The objective of the present study was to determine the immunomodulatory role of thymoquinone (TQ) regarding its effect on the production of nitric oxide (NO) by rat peritoneal macrophages. Under certain conditions, macrophagesand certain other cells can produce high concentrations of NO from its precursor L-arginine via inducible nitricoxide synthase (iNOS)pathway. TQ has been established as the major component of the oil extracted from Nigella saliva plant seeds, which is being used frequently in herbal medicine. TQ (IC50 1.4-2.76 microM) dose- and time-dependently reduced nitrite production, a parameter for NO synthesis, in supematants of lipopolysaccharide (LPS)-stimulated (5 microg/ml) macrophages without affecting the cell viability. The protein level of iNOS in peritoneal macrophages was also decreased by TQ in a concentration-dependent manner. In addition, TQ inhibited the increase in iNOS mRNA expression induced by LPS indicated by reverse transcription-polymerase chain reaction (RT-PCR). These inhibitory effects of TQ were confirmed by immunofluorescence staining of iNOS in macrophages which showed decreased immunoreactivity for iNOS after treatment with TQ if compared with the control LPS-stimulated cells. These results suggest that TQ suppresses the production of NO by macrophages; an effect which may be useful in ameliorating the inflammatory and autoimmune conditions.

An electrophysiological study of excitatory purinergic neuromuscular transmission in longitudinal smooth muscle of chicken anterior mesenteric artery

1 The object of the present study was to clarify the neurotransmitters controlling membrane responses to electrical field stimulation (EFS) in the longitudinal smooth muscle cells of the chicken anterior mesenteric artery. 2 EFS (5 pulses at 20 Hz) evoked a depolarization of amplitude 19.7±2.1 mV, total duration 29.6±3.1 s and latency 413.0±67.8 ms. This depolarization was tetrodotoxin (TTX)‐sensitive and its amplitude was partially decreased by atropine (0.5 μM); however, its duration was shortened by further addition of prazosin (10 μM). 3 Atropine/prazosin‐resistant component was blocked by the nonspecific purinergic antagonist, suramin, in a dose‐dependent manner, indicating that this component is mediated by the neurotransmitter adenosine 5′‐triphosphate (ATP). 4 Neither desensitization nor blocking of P2X receptor with its putative receptor agonist α,β‐methylene ATP (α,β‐MeATP, 1 μM) and its antagonist pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulfonic (PPADS, up to 50 μM), had significant effect on the purinergic depolarization. In contrast, either desensitization or blocking of P2Y receptor with its putative agonist 2‐methylthioATP (2‐MeSATP, 1 μM) and its antagonist Cibacron blue F3GA (CBF3GA, 10 μM) abolished the purinergic depolarization, indicating that this response is mediated through P2Y but not P2X receptor. 5 The purinergic depolarization was inhibited by pertussis toxin (PTX, 600 ng ml−1). Furthermore, it was significantly inhibited by a phospholipase C (PLC) inhibitor, U‐73122 (10 μM), indicating that the receptors involved in mediating the purinergic depolarization are linked to a PTX‐sensitive G‐protein, which is involved in a PLC‐mediated signaling pathway. 6 Data of the present study suggest that the EFS‐induced excitatory membrane response occurring in the longitudinal smooth muscle of the chicken anterior mesenteric artery is mainly purinergic in nature and is mediated via P2Y purinoceptors.

INFLUENCE OF MONENSIN ON FERTILITY IN RATS

1. Monensin was given orally to female rats at two dose levels (1.75 and 3.50 mg/kg body weight) over the period of 9‐17 days of pregnancy where organogenesis of fetuses occur. The dams were killed on the nineteenth day of gestation and their fetuses were subjected to morphological, visceral and skeletal examination. The small dose of monensin increased the number of resorbed and dead fetuses and induced marked retardation in growth of viable fetuses, but visceral or skeletal defects in these fetuses were not seen. Large doses produced fetal resorption in all dams and no viable fetuses were delivered.