Triton Hyperlipemia in Dogs

Abstract

In a previous paper (1) it was shown that triton WR-1339, I a non-ionic surface-active agent, produces, in vitro, notable physical and chemical changes of serum lipoproteins and chylomicrons. I t was assumed that if similar alterations occurred in vivo, they might be partially responsible for the hyperlipemia that had been described in rabbits (2), guinea pigs (2, 3), mice (4), and rats (5) following administration of the detergent. To test this assumption, 14 dogs were given prolonged intravenous treatment with triton. Overt hyperlipemia developed in all animals, and they died within 4 months after receiving the first injection of the detergent. The changes in plasma lipids and lipoproteins and the clinicopathologic findings will be described. Methods and ProceduresAnimals and D/et.--The animals used were male mongrel dogs, from 1 to 2 years of age, which weighed between 9 and 14 kg. They were kept in single cages and were consistently fed a diet that was 61 per cent carbohydrate, 32 per cent protein, and 7 per cent fat. The amount of food offered daily furnished about 1300 calories, 2 195 calories or 15 per cent of which was due to fat. Blood samples, for chemical analyses, were drawn from the femoral vein weekly, after a fasting period of about 12 hours.

In vitro and in vivo interactions of Triton 1339 with plasma lipoproteins of normolipidemic rhesus monkeys. Preferential effects on high density lipoproteins.

“…The involvement of the reticulo-endothelial system in dogs receiving Triton WR-1339 has been documented. 13 In those studies, a marked accumulation of lipid-laden macrophages in the spleen, liver, lymph nodes, and arteries was observed after the chronic administration of Triton. Still used electron microscopy to demonstrate 40 the presence of Triton-lipid complexes in the endothelium of the arterial intima in rats and rabbits given several intravenous injections of Triton WR-1339.…”

“…Based on past and current studies in this laboratory 12 ' 13 and studies by Ishikawa and Fidge, 15 we can state that the early Triton lesion is confined to the HDL class, which is known to play several functional roles in lipid metabolism. 18 In this context, Triton WR-1339 appears to be a very useful probe for studying the structure and function of HDL both in normo-and hyperlipidemic animals.…”

“…al alteration of HDL may account for the hyperlipidemia following the intravenous injection of Triton. An accumulation of VLDL in animals treated with Triton WR-1339 has been noted in dogs, 13 rats, 15 and squirrel monkeys 11 and has been attributed to abnormalities in VLDL-LDL conversion secondary to changes in HDL structure. 15 The displacement of apo E from the HDL particles may also have contributed to the alteration in HDL catabolism.…”

Changes in coagulative and fibrinolytic activities in Triton WR-1339-induced hyperlipidemia in rats.

“…The increase of WBC counts in rats with severe hyper lipidemia induced by 300 mg/ kg of T-WR might be explained by an inflammatory reaction such as an acute phase reactive response. Furthermore, large amounts of T WR may have altered the permeability of the vascular endothelium and/or the vascular smooth muscle through a direct combination of the detergent with the lipoprotein lipids of the cell membranes (31). These results indicate that the intravenous injection of 200 mg/kg of T-WR is suitable for the experi mental model of hyperlipidemia in rats.…”

“…In fact, we observed hematuria, hamafecia and hemolysis in some rats treated with 300 mg/ kg of T-WR. Scanu et al reported that the osmotic fragility of the red cells increased proportionally to the amount of T-WR employed (31). Since T-WR as a detergent has a hemolytic side effect, large doses of T-WR might induce the decrease in RBC counts and Hb values.…”