Synthesis and hypolipidaemic evaluation of a series of alpha-asarone analogues related to clofibrate in mice.

A series of alpha-asarone analogues related to clofibrate, containing an acetic acid group at C-2 of the aromatic ring, has been prepared as the acids or as the ethyl and methyl esters. The corresponding alcohols were also synthesized by reduction of the ethyl esters. The compounds were examined in hyperlipidaemic male mice to evaluate their ability to modify serum lipoprotein cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides after oral administration of 40 and 80 mg kg(-1) for 6 days. Except for methyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate at either dose, these clofibrate-related phenoxyacetic acid derivatives were found to have significant hypocholesterolaemic activity. Levels of low-density lipoprotein cholesterol and triglycerides were significantly reduced and those of high-density lipoprotein cholesterol were elevated. 2-Methoxy-5-nitro-4-(2-propenyl)phenoxyacetic acid was active at both doses in all the tests. Clofibrate (150 mg kg(-1)) was more potent at reducing low-density lipoprotein cholesterol. No activity was detected for the alcohol derivatives. These preliminary results suggest that this class of compound might have more promise as potential hypolipidaemic agents than other alpha-asarone derivatives. Further investigation and characterization should be performed to determine the mode of action of these agents on lipid metabolism.

Experimental pulmonary schistosomiasis: lack of morphological evidence of modulation in schistosomal pulmonary granulomas.

Numerous pulmonary schistosome egg granulomas were present in mice submitted to partial portal vein ligation (Warren's model). The granulomas were characterized by cellular aggregations formed within alveolar tissue. Main cellular types were macrophages (epithelioid cells), eosinophils, plasma cells and lymphocytes. These cells were supported by scanty fibrous stroma and exhibited close membrane contact points amongst themselves, but without forming specialized adhesion apparatus. When granulomas involved arterial structures, proliferation of endothelial and smooth muscle cells occurred and fibrosis associated with angiogenesis became more evident. Granulomas formed around mature eggs in the pulmonary alveolar tissue presented approximately the same size and morphology regardless of the time of infection, the latter being 10, 18 and 25 weeks after cercarial exposure. This persistence of morphological appearance suggests that pulmonary granulomas do not undergo immunological modulation, as is the case with the granulomas in the liver and, to a lesser extent, in the intestines. Probably, besides general immunological factors, local (stromal) factors play an important role in schistosomal granuloma modulation.