Nobutaka Kurihara

Detection of a carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, in airborne particles and Diesel-exhaust particles

A carcinogen, 2-amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP), has been measured in airborne particles, diesel-exhaust particles, and incineration ash from garbage-burning plants. PhIP was found in all kinds of samples. In the light of the present results, together with the previous findings that PhIP was present in cooked foods and cigarette smoke, PhIP is likely to be an ubiquitous environmental pollutant. These observations also suggest that PhIP may be formed through the combustion process.

Increases in Glomerular Eicosanoid Production in Rats with Bilateral Ureteral Obstruction Are Mediated by Enhanced Enzyme Activities of Both the Cyclooxygenase and 5-Lipoxygenase Pathways

Abstract Glomeruli isolated from rats with bilateral ureteral obstruction (BUO) of 24 hr duration produced significantly greater amounts of prostaglandin (PG) E2, 6-keto-PGF1α, thromboxane B2, and leukotriene B4 than glomeruli isolated from sham-operated control (SOC) rats. To examine the mechanisms underlying the greater production of eicosa-noids by glomeruli isolated from rats with BUO, we measured the activities of enzymes related to eicosanoid formation such as cyclooxygenase, 5-lipoxygenase, PGE2 isomerase, and PGI2 and thromboxane synthase in glomeruli isolated from SOC rats and rats with BUO. Glomeruli isolated from rats with BUO had a significantly increased activity of cyclooxygenase with de novo synthesis of this enzyme and a markedly augmented activities of PGE2 isomerase and both PGI2 and thromboxane synthases relative to glomeruli isolated from SOC rats. Similarly, the activity of membrane-bound 5-lipoxy-genase, the active location of this enzyme, was significantly greater in glomeruli isolated from rats with BUO than in glomeruli isolated from SOC rats. Thus, BUO of 24 hr duration enhances the glomerular production of eicosanoids via the activation of enzymes in both the cyclooxygenase and 5-lipoxygenase pathways.

Mechanism of the decreased eicosanoid production in vitro in response to angiotensin II in glomeruli of rats with bilateral ureteral obstruction

Summary: Glomeruli isolated from rats with bilateral ureteral obstruction (BUO) of 24 h duration synthesized significantly greater amounts of prostaglandin (PG)E2, 6‐keto PGF1a, thromboxane (Tx)B2 and leukotriene (LT)B4 than glomeruli isolated from sham‐operated control (SOC) rats. Glomeruli isolated from SOC rats produced increased amounts of these four eicosanoids compared to basal conditions when 100 nmol/L angiotensin II (AII) was added in vitro to the preparations. However, no significant increases in glomerular eicosanoid production were seen under these conditions in glomeruli of rats with BUO. to examine the mechanims underlying imparied eicosanoid production in glomeruli of rats with BUO exposed to AII in vitro, we measured the activities of phosphatidylethanolamine (PE)‐specific phospholipase A2 (PLA2), 5‐lipoxygenase and the cyclo‐oxygenase pathway enzymes including cyclo‐oxygenase, PGE2 isomerase and PGI2 and Tx synthases under basal conditions and after addition of 100 nmol/L AII in vitro in glomeruli isolated from SOC rats and rats with BUO of 24 h duration. the basal activities of all of these enzymes were significantly greater in glomeruli of rats with BUO compared to SOC rats. In glomeruli of SOC rats, the activities of these enzymes were markedly increased when exposed to 100 nmol/L AII in vitro compared to basal conditions. By contrast, no significant changes in the activities of enzymes involved in eicosanoid formation above baseline were seen in glomeruli of rats with BUO exposed to AII in vitro. the production rates of eicosanoids paralleled the activities of these enzymes under basal and AII‐stimulated conditions in glomeruli obtained from SOC rats and rats with BUO. Thus, the lack of increased levels of PGE2, 6‐keto PGF1a, TxB2 and LTB4, when glomeruli of rats with BUO of 24 h duration are exposed to 100 nmol/L AII in vitro, maybe due mainly to either the action of PE‐specific PLA2 or the combined action of PE‐specific PLA2, cyclo‐oxygenase pathway enzymes and 5‐lipoxygenase set at, or near, maximum levels as a consequence of BUO.