Lipid effects of a phenolic ether (Su-13437) in the rat: Comparison with CPIB

Best, Maurice M.; Duncan, Charles H.

doi:10.1016/0021-9150(70)90095-x

Cited by 24 publications

(9 citation statements)

References 9 publications

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“…Nafenopin, like CPIB, is a phenolic ether which produces in rats a significant reduction in serum triglycerides, but does not significantly reduce the serum cholesterol (24) . Serum glycerol-glycerides were significantly lowered in rats and mice given nafenopin in the present investigation .…”

Section: Discussionmentioning

confidence: 99%

“…Recently we have demonstrated that administration of nafenopin (2-methyl-2[p-(l,2,3,4tetrahydro-l-nephthyl)phenoxy]-propionic acid ; Su-13437) to male rats, by gavage at 100 mg/kg body weight daily for 1-2 wk, results in a marked proliferation of hepatic microbody profiles with simultaneous increase in catalase activity (22) . Nafenopin is structurally related to CPIB and on an equivalent weight basis is approximately five times as potent as CPIB in producing hypolipidemia and hepatomegaly (23,24) . In the present investigation varying concentrations of nafenopin were administered in ground Purina Chow ad lib to both male and female rats, wild type (Csa strain) mice and acatalasemic (Cs' strain) mice, in order to determine the doseresponse relationship and to ascertain the species and sex differences, if any, in microbody proliferative response and inducibility of liver catalase .…”

Section: Introductionmentioning

confidence: 99%

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Nafenopin-Induced Hepatic Microbody (Peroxisome) Proliferation and Catalase Synthesis in Rats and Mice

Reddy

Azarnoff

Svoboda

et al. 1974

The Journal of Cell Biology

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Nafenopin (2-methyl-2[p-(1,2,3,4-tetrahydro-l-naphthyl)phenoxy]-propionic acid ; Su-13437), a potent hypolipidemic compound, was administered in varying concentrations in ground Purina Chow to male and female rats, wild type (Csa strain) mice and acatalasemic (Csb strain) mice to determine the hepatic microbody proliferative and catalase-inducing effects . In all groups of animals, administration of nafenopin at dietary levels of 0 .125% and 0 .25% produced a significant and sustained increase in the number of peroxisomes . The hepatic microbody proliferation in both male and female rats and wild type Csa strain mice treated with nafenopin was of the same magnitude and was associated with a two-fold increase in catalase activity and in the concentration of catalase protein . The increase in microbody population in acatalasemic mice, although not accompanied by increase in catalase activity, was associated with a twofold increase in the amount of catalase protein .The absence of sex difference in microbody proliferative response in nafenopin-treated rats and wild type mice is of particular significance, since ethyl-a-p-chlorophenoxyisobutyrate (CPIB)-induced microbody proliferation and increase in catalase activity occurred only in males . Nafenopin can, therefore, be used as an inducer of microbody proliferation and of catalase synthesis in both sexes of rats and mice . The serum glycerol-glycerides were markedly lowered in all the animals given nafenopin, which paralleled the increase in liver catalase . All the above effects of nafenopin were fully reversed when the drug was withdrawn from the diet of male rats . During reversal, several microbody nucleoids were seen free in the hyaloplasm or in the dilated endoplasmic reticulum channels resulting from a rapid reduction in microbody matrix proteins after the withdrawal of nafenopin from the diet . Because of microbody proliferation and catalase induction with increasing number of hypolipidemic compounds, additional studies are necessary to determine the interrelationships of microbody proliferation, catalase induction, and hypolipidemia .

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nafenopin-Induced Hepatic Microbody (Peroxisome) Proliferation and Catalase Synthesis in Rats and Mice

Reddy

Azarnoff

Svoboda

et al. 1974

The Journal of Cell Biology

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“…When S-8527 was given to rats, the total content of liver triglycerides was significantly decreased; 28.2 mg per liver with 100 mg/kg of S-8527 and 40.7 mg in control. On the contrary, because of hepatome galy produced by clofibrate treatment, total content of triglycerides in 300 mg/kg of clo fibrate treated group (66.1 mg per liver) was greater than that in control (41.1 mg) as re ported by Best et al (12) and Gould et al (13). In addition, in Triton injected rats, the lowering effect of serum triglycerides was observed in S-8527 treated groups only.…”

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confidence: 81%

Hypolipidemic Effect of a New Aryloxy Compound, S-8527, in Experimental Animals

Suzuki

Aono

Nakatani

1974

Japanese Journal of Pharmacology

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Abatract-The hypolipidemic action of 1,1-bis [4'-(l"-carboxy-1"-methylpropoxy)phenyl] cyclohexane (S-8527) was studied in rats, mice and rabbits under various ex perimental conditions to compare the effects with those of clofibrate. Oral ingestion of S-8527 to normal rats for 7 days lowered serum triglycerides and cholesterol by about 27% at 1 mg/kg and 20% at 3 mg/kg, respectively. The hypolipidemic effect of S-8527 was considered to be twenty to thirty times more potent than that of clo fibrate but a hepatomegalic effect of S-8527 was not observed at its effective dose ranging from 1 to 30 mg/kg. S-8527 at 3 mg/kg decreased liver triglyceride concen tration by about 20% but the decrease of triglyceride concentration was not ob served in clofibrate treated groups. Liver cholesterol concentration was not decreased with any of the doses of S-8527 while clofibrate decreased liver cholesterol concen tration by about 20% at 300 mg/kg. However, there were no differences in total content of cholesterol in liver between S-8527 and clofibrate treated groups. With Triton injected rats, a single oral dose of 100 mg/kg of S-8527 depressed the increase of serum triglycerides by about 50% while clofibrate did not. In glycerol-fed rats, S-8527 decreased serum and liver triglycerides more effectively than clofibrate, and in normal mice and cholesterol-fed mice, S-8527 was found to be more active than clo fibrate, however the hepatornegalic effect of S-8527 was less than that of clofibrate. Hypolipidemic effects in rabbits were not observed with either S-8527 or clofibrate.During a course of studies on hypolipidemic activity of various compounds synthe sized in our laboratory, we found that a new aryloxy compound, 1,1-bis [4'-(1 "-carboxy 1 "-methylpropoxy)phenyl] cyclohexane (S-8527) caused a marked decrease in serum lipids level at a smaller dose than that required for clofibrate and that there was a less hepatic effect at the effective dose in rats (1, 2). As studies concerning the dose-response relation ship in a wider range of doses of S-8527 were not included in the previous report (1), we do so herein.Recently, several new compounds of this class have been reported to show a lipid-low ering effect in rats and humans at a smaller dose than that required for clofibrate, but one of the general biological features of these compounds is that there is a marked hepatome galic effect in parallel with the hypolipidemic activity in the rodent (3-7).In the present study, an elucidation of the dose=response relationship for hypolipi demic activity of S-8527 in normal rats and its effect on hyperlipidemia induced by Triton injection, cholesterol feeding and glycerol loading in rats and mice are given. Hypolipidemic activity of S-8527 in normal mice and rabbits is also investigated.

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“…This speculation is supported by the similarities in chemical structure of the two drugs, both being aryloxyisobutyric acids, and by their similar hepatomegalic effect in the rat. 12 Any conclusions regarding the relative effectiveness of Su-13437 and CPIB must be tentative. Although the conditions under which the responses of these patients to CPIB were determined were in general similar to those of this study, they were not identical with regard to either duration of treatment or frequency of observations.…”

Section: Sgptmentioning

confidence: 99%

Effects of a Phenolic Ether, Su-13437, on Serum Cholesterol, Triglyceride, and Transaminase Levels of Human Subjects

Duncan

Best

1970

Circulation

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The hypolipidemic activity of the phenolic ether, 2-methyl-2-[p-(1,2,3,4-tetrahydro-1naphthyl)-phenoxy]-propionic acid (Su-13437, Ciba) has been studied in 10 hypercholesterolemic patients. The patients were studied at 3-week intervals during 30 weeks of placebo administration and a 30-week period of treatment with Su-13437, 400 mg daily.Individual mean serum total cholesterol during administration of placebo ranged from 255 to 609 mg/100 ml and during treatment from 187 to 493, the mean reduction being 22%. Five of the subjects were also hypertriglyceridemic, with individual mean levels of triglycerides during placebo periods ranging from 159 to 1247 mg/100 ml. During treatment with Su-13437 mean triglyceride levels of these five patients ranged from 81 to 314 mg/ 100 ml, a mean reduction of 51%.The drug was well tolerated and its only effect on the hematologic and biochemical tests for possible toxicity was an increase in SGOT and SGPT levels in two patients, the levels being maximal between the sixth and ninth weeks of drug administration and returning later toward pretreatment values despite continuation of Su-13437.

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Lipid effects of a phenolic ether (Su-13437) in the rat: Comparison with CPIB

Cited by 24 publications

References 9 publications

Nafenopin-Induced Hepatic Microbody (Peroxisome) Proliferation and Catalase Synthesis in Rats and Mice

Nafenopin-Induced Hepatic Microbody (Peroxisome) Proliferation and Catalase Synthesis in Rats and Mice

Hypolipidemic Effect of a New Aryloxy Compound, S-8527, in Experimental Animals

Effects of a Phenolic Ether, Su-13437, on Serum Cholesterol, Triglyceride, and Transaminase Levels of Human Subjects

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