Ocimum basilicum seed extracts were found to possess significant anti-ulcer activity against ethanol-induced ulceration in experimental animal models. Three groups of adult male rats were used, with each group consisting of six rats. Oral administration of absolute ethanol to rats pre-treated with 10% Tween 20® (Group 1) produced extensive haemorrhagic lesions of the gastric mucosa. Rats orally pre-treated with O. basilicum extract suspended in 10% Tween 20® (Group 2) or cimetidine in 10% Tween 20® (Group 3), 30 min before oral administration of absolute alcohol had significantly reduced (p
Six groups of adult Sprague-Dawley rats were orally administered with a variety of treatments to elucidate their cytoprotective effects. Absolute ethanol combined with HCl was used to induce gastric lesions in rats. Aqueous and ethanol extracts of Chromolaena odorata, a famous folk herb for treating skin wounds were evaluated to determine their protective effect on gastric mucosa. In this study, aqueous extract and ethanol extract of C. odorata were combined with honey. In addition, honey alone and honey combined with cimetidine were also evaluated. Rat stomachs were examined grossly and histologically. Results were expressed as inhibition percentage. The honey and aqueous extract combination showed the highest inhibition percentage (72.67%) followed by honey and ethanol extract (58.92%), honey and cimetidine (56.55%) and the lowest was honey alone (46.74%). However, there were no significant differences between the effects of aqueous and ethanol extracts of C. odorata and honey in promoting cytoprotective effects and this may be due to the small sample size. Nevertheless, these results suggest that C. odorata and honey may be beneficial in treating induced gastric mucosal injury.
To enhance the stability of the anticancer drug gemcitabine (2'-deoxy-2',2'-difluorocytidine), it was conjugated to poly-l-glutamic acid (PG-H) via a carbodiimide reaction. The synthesised poly-l-glutamic acid-gemcitabine (PG-G) was purified and characterised by using SDS-PAGE to estimate its molecular weight, HPLC to determine its purity and degree of drug loading, and NMR to elucidate the structure. In vitro aqueous hydrolytic studies showed that the gemcitabine release from the polymeric drug conjugate was pH dependent, and that the conjugation to PG-H improved its stability in human plasma. The release of the bound gemcitabine from PG-G in plasma was mediated by a hydrolytic process. It began with a lag phase, followed by linear release between 12 and 48h, and reached equilibrium at 72h with 51% of the gemcitabine released. In vitro cytotoxicity studies using MCF-7 and MDA-MB-231 human mammary cancer cells, as well as human dermal fibroblasts (HDF), showed that PG-G displayed a lower dose dependent cytotoxic effect with respect to the parent drug gemcitabine. On the other hand, in 4T1 mouse mammary tumour cells, PG-G and gemcitabine showed similar toxicities. Gemcitabine was more than likely released hydrolytically from PG-G and taken up by MCF-7, MDA-MB-231 and HDF, whereas both released gemcitabine and PG-G were taken up by 4T1 to mediate the observed cytotoxicities. The improved stability and extended sustained release profile may render PG-G a potential anticancer prodrug.
An antisense oligodeoxynucleotide (As-ODN) to the 3' untranslated region of the mRNA sequence expressing the intracellular adhesion molecule-1 (ICAM-1) was employed to determine ICAM-1's role in renal ischaemia-reperfusion injury in the rat. Wistar-Kyoto rats receiving i.v. either lipofectin-As-ODN (As-ODN group), lipofectin-reverse ODN (Rv-ODN group) or lipofectin (ischaemia control group) 8 h prior to study were anaesthetized and subjected to 30 min of renal artery occlusion. Renal haemodynamic and excretory parameters were monitored before and after renal ischaemia. On termination of the study renal tissue was subjected to histological and Western blot analysis. Renal blood flow decreased in the 3 h post-ischaemia period in the ischaemia control and Rv-ODN groups, but was maintained in the As-ODN group. Glomerular filtration rate was depressed initially but gradually increased to 10% above basal levels in the ischaemia control and Rv-ODN groups, but was below basal levels (20%) in the As-ODN group. There was a three- to fourfold increase in sodium and water excretion following ischaemia in the ischaemia control and reverse-ODN groups but not in the As-ODN treated group. The As-ODN ameliorated the histological evidence of ischaemic damage and reduced ICAM-1 protein levels to a greater extent in the medulla than cortex. These observations suggested that in the post-ischaemic period afferent and efferent arteriolar tone was increased with a loss of reabsorptive capacity which was in part due to ICAM-1. The possibility arises that the action of ICAM-1 at vascular and tubular sites in the deeper regions of the kidney contributes to the ischaemia-reperfusion injury.