Flupenthixol and cefotiam: effects on vitamin A metabolism in rats

Schindler, R. N.; Fielenbach, Tanja; Rave, Gerhard

doi:10.1079/bjn20041236

Cited by 3 publications

(5 citation statements)

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“…As a reflection of gavage-related stress during the pre-chronic interval, significant decreases in plasma retinol concentration from baseline were observed, as anticipated (Schindler et al 2004). The plasma retinol concentrations were, however, somewhat lower for those rats assigned to receive amiodarone or trimeprazine in acute administration than for control rats (Fig.…”

Section: Vehiclesupporting

confidence: 70%

“…4), and chronic treatment as one that took more than 10 d (interval 12 -28 d; Fig. 4) to facilitate the comparison of our present results with previous ones (Schindler et al 2004). Drug £ time interaction terms were all significant for plasma retinol concentrations between days 0 and 8 after amiodarone (P,0•001) and trimeprazine (P,0•003), but the drug £ time interaction term was not significant after dosing vehicle (P¼0•254).…”

Section: Resultsmentioning

confidence: 53%

“…Male Brown Norway rats (weight 214-356 g) were obtained from the Zentralinstitut für Versuchstierzucht (Hannover, Germany). Upon arrival, rats were individually housed and kept in an environmentally controlled laboratory as described in our previous publication (Schindler et al 2004). Tap water and nutritionally adequate diet (Rodent diet #1314; Altromin, Lage, Germany), containing vitamin A (15 000 IU vitamin A/kg diet), were available at all times except at the end (days 26 and 27) of the experiment.…”

Section: Sources Of Pharmacological Agents Chemicals and Experimentamentioning

confidence: 99%

“…Changes in hepatic retinyl ester composition require a concerted adaptation of vitamin A metabolism, adjusted by hydrolytic and synthetic activities for esterified retinol. Therefore, this and previous studies (Schindler et al 2002(Schindler et al , 2004) also sought to determine whether in vivo dosing with REH inhibitors could produce subsequent alterations in the liver vitamin A ester profile. The major finding of this investigation was that treatment of Brown Norway rats with amiodarone caused a considerable increase in the relative amounts of retinyl linoleate and retinyl myristate, mainly at the expense of the retinyl palmitate and retinyl oleate fraction, whereas trimeprazine failed to show such an effect.…”

Section: Vehiclementioning

confidence: 99%

“…Vitamin A metabolism has been shown to be susceptible to therapeutic agents, and a few such interactions have been directly observed clinically, for example with the antibiotic procaine penicillin, which results in night blindness (Haubold et al 1953). Recent studies carried out in vivo have shown that cefotiam and flupenthixol also can operate as vitamin A antagonists (Schindler et al 2004). The broad-spectrum antibiotic cefotiam shares structural features with penicillins, and the thioxanthene drug flupenthixol has structural characteristics related to those of the phenothiazines.…”

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confidence: 99%

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A comparative study on the effects of oral amiodarone and trimeprazine, twoin vitroretinyl ester hydrolase inhibitors, on the metabolic availability of vitamin A in rats

2005

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Amiodarone, an antiarrhythmic drug, and trimeprazine, an antipsychotic drug, are both in vitro inhibitors of retinyl ester hydrolase. To determine whether these agents have deleterious effects on aspects of vitamin A metabolism, Brown Norway rats (n 18) were treated at clinically equivalent doses once daily for 26 d with either oral drug. On day 27, a tolerance test was used to determine whether these agents interfered with vitamin absorption. During the first 8 d, the plasma retinol level declined in all animals. Between days 12 and 27, it rose to near pre-treatment concentrations in the control and trimeprazine groups and remained relatively constant at low levels (P,0·001) in the amiodarone group. The intestinal absorption of vitamin A was reduced (P,0·05) in the amiodarone group compared with the placebo and trimeprazine groups, which did not differ significantly from each other. At the end of the 4-week treatment period, hepatic retinyl ester hydrolase activity was lower in the drug-dosed rats (P¼ 0·06 for amiodarone) than in the controls. With regard to effects on liver reserves, drug treatment resulted in vitamin A depletion (P,0·019), and distinctive patterns of retinol and its esters were seen in response to dosing. In conclusion, amiodarone and trimeprazine have been shown to influence different aspects of retinoid metabolism, namely absorption, storage and transport. In clinical practice, the routine unmonitored use of these drugs and the suggestion that these agents be taken with meals are not recommended. Amiodarone-vitamin A interaction: Trimeprazine -vitamin A interaction: Retinyl ester hydrolaseVitamin A is a fat-soluble vitamin present in animal-based diets as retinyl esters (retinol esterified to fatty acids; Schindler et al. 1987). Once absorbed, liberated retinol is converted by the activity of acyltransferase back to esterified retinol, in which form vitamin A is targeted to the liver, its primary site of storage MacDonald & Ong, 1988). Central to vitamin A handling by the organism is the reversible, enzymatic conversion of retinyl esters to retinol (for reviews see Harrison, 1998).Retinyl ester-splitting enzymes are found ubiquitously, in many tissues, and it is generally assumed that their function, activity and regulation depend on the enzyme location. Whereas retinolliberating enzymes from pancreas and intestinal brush border are a pre-requisite for the full absorption of dietary vitamin A (Lombardo & Guy, 1980;Rigtrup et al. 1994), isoenzymes in eyes provide free retinol as an intermediate in rhodopsin regeneration (Tsin & Lam, 1986). In the liver, the central organ in maintaining body retinol homeostasis, the retinyl ester-converting enzymes are involved in the hydrolysis of vitamin A esters delivered to the hepatocytes via the receptor-mediated endocytosis of chylomicron remnants (Blomhoff et al. 1982) and the generation of free retinol from its storage form as esters (Goodman & Blaner, 1984). The liberated retinol acts as precursor for re-esterification for storage (Blaner et al. 198...

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Section: Vehiclesupporting

confidence: 70%

Section: Resultsmentioning

confidence: 53%

Section: Sources Of Pharmacological Agents Chemicals and Experimentamentioning

confidence: 99%

Section: Vehiclementioning

confidence: 99%

mentioning

confidence: 99%

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