Increase in hepatic mitochondria on administration of ethyl α-<i>p</i>-chlorophenoxyisobutyrate to the rat

Kurup, C. K. Ramakrishna; Aithal, H. N.; Ramasarma, T.

doi:10.1042/bj1160773

Cited by 118 publications

(36 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both activities amounted to maximally 2% of the original activity in the liver homogenate. This extent of contamination compares favourably with data in the literature [20,21].…”

Section: Methodssupporting

confidence: 72%

The interaction of adriamycin with cardiolipin in model and rat liver mitochondrial membranes

Nicolay

Timmers

Spoelstra

et al. 1984

Biochimica et Biophysica Acta (BBA) - Biomembranes

View full text Add to dashboard Cite

The interaction of adriamycin with cardiolipin in model membranes and in various membrane preparations derived from rat liver mitochondria was studied and the results are analyzed in the light of a possible specific interaction between adriamycin and cardiolipin. It was found that adriamycin binds to cardiolipin-containing model membranes with a fixed stoichiometry of two drug molecules per cardiolipin. Furthermore, the extent of drug complexation by mitochondria and mitoplasts (inner membrane plus matrix) is in reasonable agreement with their cardiolipin content. In contrast, adriamycin-binding curves of inner membrane ghosts and submitochondrial particles reveal considerable association to an additional site, presumably RNA. The evidence for the potential importance of RNA as a target comes from experiments on outer membranes and microsomes which both appear to bind substantial amounts of adriamycin. Removal of the major part of the RNA associated with these fractions by EDTA treatment is accompanied by a dramatic reduction of binding capacity. We propose that endogenous RNA present in mitochondria and mitoplasts is not accessible for adriamycin at low concentrations of the drug due to the presence of an intact lipid barrier. This potential site comes to expression in ghosts and submitochondriai particles, due to the absence of an intact lipid bilayer and due to the inside-out orientation of the limiting membrane, respectively. Electron microscopical studies show that adriamycin induces dramatic changes in mitochondrial morphology, similar to the uncoupler-induced effects described by Knoll and Brdiczka (Biochim. Biophys. Acta 733, 102-110 (1983)). Adriamycin has an uncoupling effect on mitochondrial respiration and oxidative phosphorylation. The concentration dependence of this effect correlates with the adriamycin-binding curve for mitochondria which implies that only bound adriamycin actively inhibits respiration.

show abstract

“…Both activities amounted to maximally 2% of the original activity in the liver homogenate. This extent of contamination compares favourably with data in the literature [20,21].…”

Section: Methodssupporting

confidence: 72%

The interaction of adriamycin with cardiolipin in model and rat liver mitochondrial membranes

Nicolay

Timmers

Spoelstra

et al. 1984

Biochimica et Biophysica Acta (BBA) - Biomembranes

View full text Add to dashboard Cite

show abstract

“…An increase in hepatic content of NA D and in the ratio of NAD: NADH has been observed in rats receiving clofibrate (45); the latter change is consistent with our observations. The content of mitochondria in liver increases substantially in rats receiving a large dose of clofibrate (0.5 g/lOO g of diet) (46). These mitochondria have normal oxidative activity and respiratory control.…”

Section: Results-mentioning

confidence: 93%

Mechanism of the Hypolipemic Effect of Clofibrate in Postabsorptive Man

Wolfe¹,

Kane²,

Havel³

et al. 1973

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T Splanchnic metabolism of triglycerides and other major substrates was studied in the postabsorptive state in normotriglyceridemic and hypertriglyceridemic human subjects wh}o received A g of clofibrate four times daily for 3 wNk. Transport in blood plasma of triglycerides produced in the splanchnic region was quantified by three methods: (a) measurement of the transsplanchnic gradient of '4C-labeled triglycerides during constant intravenous infusion of [1-"C]palmitate (b) chemical measurement of the transsplanchnic gradient in concenltration of triglycerides of very low density lipoproteins; and (c) determination of clearance of 14C-labeled triglycerides in extrasplanchnic tissues. The first method measures only triglycerides derived from free fatty acids and the last two measure total splanchnic production. In hypertriglyceridemic subjects treated with clofibrate, average rates of total splanchulic production of triglycerides and productioni from free fatty acids were the same as those of conmparable untreated subjects despite a consistent fall in plasma triglyceride levels. The hvpotriglyceridemic effect of the drug was therefore accompanied by improved disposal of triglycerides in extrasplanchnic tissues. In treated normotriglyceridemic subjects, unlike their untreated counterparts, total splanchnic production wvas significantly higlher than prodluction from free fatty acids.

show abstract

“…Clofibrate treatment in rats increases hepatic mitochondrial number (20) and mitochondrial oxidation (25). Although mitochondrial mass was Amounts of mRNA for control pigs are set as 100%, and data are reported as % change for clofibrate-supplemented pigs relative to control pigs.…”

Section: Discussionmentioning

confidence: 99%

Hepatic β-oxidation and carnitine palmitoyltransferase I in neonatal pigs after dietary treatments of clofibric acid, isoproterenol, and medium-chain triglycerides

Peffer

Lin

Odle

2005

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

A suckling piglet model was used to study nutritional and pharmacologic means of stimulating hepatic fatty acid beta-oxidation. Newborn pigs were fed milk diets containing either long- or medium-chain triglycerides (LCT or MCT). The long-chain control diet was supplemented further with clofibric acid (0.5%) or isoproterenol (40 ppm), and growth was monitored for 10-12 days. Clofibrate increased rates of hepatic peroxisomal and mitochondrial beta-oxidation of [1-(14)C]-palmitate by 60 and 186%, respectively. Furthermore, malonyl-CoA sensitive carnitine palmitoyltransferase (CPT I) activity increased 64% (P < 0.05) in pigs receiving clofibrate. Increased CPT I activity was not congruent with changes in message, as elevated abundance of CPT I mRNA was not detected (P = 0.16) when assessed by qRT-PCR. Neither rates of beta-oxidation nor CPT activities were affected by dietary MCT or by isoproterenol treatment (P > 0.1). Collectively, these findings indicate that clofibrate effectively induced hepatic CPT activity concomitant with increased fatty acid beta-oxidation.

show abstract

Increase in hepatic mitochondria on administration of ethyl α-p-chlorophenoxyisobutyrate to the rat

Cited by 118 publications

References 21 publications

The interaction of adriamycin with cardiolipin in model and rat liver mitochondrial membranes

The interaction of adriamycin with cardiolipin in model and rat liver mitochondrial membranes

Mechanism of the Hypolipemic Effect of Clofibrate in Postabsorptive Man

Hepatic β-oxidation and carnitine palmitoyltransferase I in neonatal pigs after dietary treatments of clofibric acid, isoproterenol, and medium-chain triglycerides

Contact Info

Product

Resources

About