M. S. Al-Humayyd

Natural honey prevents ischaemia-reperfusion-induced gastric mucosal lesions and increased vascular permeability in rats

Objective: It has been proposed that natural honey may contain a ‘sucralfate‐like’ substance. Recent studies have shown that sucralfate affords protection against ischaemia‐reperfusion‐induced injuries in the rat stomach. Therefore, the effect of honey was studied on ischaemia‐reperfusion‐induced gastric lesions, intraluminal bleeding, vascular permeability and non‐protein sulphhydryls (NP‐SH) in the rat stomach. Methods: Rats were subjected to 30min of gastric ischaemia in the presence of 100 mM HCI and reperfusion period of 60min. Intraluminal bleeding was assessed macroscopically and the gastric lesions were graded microscopically under an inverted microscope. Vascular permeability was quantified by measuring spectrophotometrically the extravasated Evans blue dye in the stomach. NP‐SH levels were measured spectrophotometrically. A luminol‐dependent chemiluminescence method was used to assess antioxidant effects of honey in vitro. Results: There were significantly more gastric lesions, more severe intraluminal bleeding, more leakage of Evans blue and depletion of NP‐SH during the reperfusion period as compared to controls. Pre‐treatment with honey (0.078‐0.625 g/kg, orally) or dimethyl sulphoxide (0.02‐0.08g/kg, intraperitoneally) 30min before the ischaemia‐reperfusion dose‐dependently reduced the gastric lesions and intraluminal bleeding and decreased the vascular permeability. Furthermore, honey reversed the ischaemia‐reperfusion‐induced depletion of NP‐SH levels and inhibited the luminol‐dependent chemiluminescence induced in a cell‐free xanthine‐xanthine oxidase system. Conclusion: These results suggest that gastric protection by honey may be a result of its antioxidant effect. It is suggested that this property of honey may be due to the presence of a ‘sucralfate‐like’ substance.

Effect of diltiazem, nifedipine and verapamil on the antinociceptive action of acetylsalicyclic acid in mice

1. Diltiazem, verapamil and nifedipine produced a dose-dependent analgesic response in mice. 2. A fixed oral dose of acetylsalicylic acid increased this analgesic response. 3. Analgesia was maintained when mice were treated chronically with calcium channel blockers alone or when combined with aspirin.

Enhancement of antithrombotic effect of aspirin by metoclopramide in rats

The potential antithrombotic effect of aspirin and metoclopramide were studied in a model of arterial thrombosis in rats. Thrombosis was produced in the abdominal aorta by the combination of local partial obstruction and intravenous administration of hypotonic saline containing 5-HT. The resulting aortic occlusion and the effects of drugs were quantified by measuring rectal temperature. Metoclopramide as well as ketanserine effectively reversed while zacopride failed to alter thrombotic effect. Metoclopramide or ketanserine when combined with aspirin enhanced the antithrombotic effect of the latter. On the other hand, co-administration of metoclopramide with ketanserine failed to show any synergistic effect. As with ketanserine, the antithrombotic effect of metoclopramide appeared to be mediated through the blockade of 5-HT2 receptors in the platelets.

Investigation of the antifibrillatory drug interactions between Amiodarone and Ibutilide in isolated, perfused Rabbit hearts

In view of the reliability of the serial‐shock method of measuring ventricular fibrillation threshold (VFT) in quantitatively assessing the antifibrillatory potency of many anti‐arrhythmic drugs and the alarming reports of the proarrhythmic effects of several anti‐arrhythmic agents, it was decided to use the above technique to study the possible interactions that may occur when anti‐arrhythmic drugs from different classes are combined. Hearts isolated from New Zealand white rabbits of either sex weighing 1.5–2 kg were perfused by the Langendorff method with McEwens solution. In six hearts, measurement of VFT was made in the absence of any drug throughout the experiments. Perfusion with either amiodarone or ibutilide produced significant, dose‐dependent increase in VFT. In addition, there was no significant difference in the increase in VFT produced by the combined infusion of 1 μmol of amiodarone and 0.01 μmol of ibutilide and the summation of the increases produced by the separate infusion of these two concentrations. This is in contrast to a significant synergistic antifibrillatory effect of the combined use of lidocaine and propranolol that was reported previously. The lack of antifibrillatory interactions between amiodarone and Ibutilide may suggest the safety of combining the two drugs in the treatment of cardiac arrhythmias. However, further studies are required to establish this in the clinical setup.

Enhancement of anti-inflammatory effects of calcium channel blockers by allopurinol and dimethylsulphoxide

The effects of the calcium channel blockers, nifedipine, verapamil and flunarizine, and the antioxidants, allopurinol and dimethylsulphoxide, were investigated on carrageenan-induced rat paw oedema and changes in vascular permeability. Paw volume was measured by using a plethysmometer and vascular permeability was quantified by measuring the extravasated Evans blue dye 3 h after injecting the phlogistic agent. Intraperitoneal administration of nifedipine (1,2 and 4 mg/kg), verapamil (5, 10 and 20 mg/kg), flunarizine (2.5, 5 and 10 mg/kg), allopurinol (6.25, 12.5 and 25 mg/kg) and dimethylsulphoxide (20, 40 and 80 mg/kg) 30 min before carrageenan, dose dependently inhibited oedema formation and increased vascular permeability. Co-administration of the lowest doses of calcium channel blockers with the lowest doses of antioxidants produced synergistic inhibitory effects. These results indicate that both calcium influx and oxygen-derived free radicals are involved in carrageenan-induced inflammatory responses. Thus, the synergistic effects of their combination may be due to the blockade of calcium entry and reduction in the generation of oxygen-derived free radicals.