ethylmorphine and Body-Weight

To investigate whether or not there is a beneficial effect of diltiazem (D) on cyclosporine A (CsA) nephrotoxicity, renal function, CsA blood levels, and effects of CsA on biotransformation in the liver and on lipid peroxidation were characterized in rats. A single administration of D (60 mg/kg b.wt.) reduced urinary volume (UV), GFR and excretion of Na+ and K+, whereas a single dose of CsA (60 mg/kg b.wt.) alone had no respective effects. P-aminohippurate excretion was almost equal in all groups. Lower doses of D (and CsA) were without effects. After repeated CsA treatment a retardation in body weight gain was seen, with little effect of a co-administration with D hereon. In all tests, thymus mass was reduced by CsA, the weight of spleen, liver, adrenal glands, and kidney were not generally affected by any of the treatments. Furthermore, after repeated administration of CsA and/or D, urinary volume, GFR and Na+ excretion were reduced by CsA, too. Electrolyte concentrations in plasma showed no evident changes by any of the treatments for Na+ and Ca2+. After long time treatment, CsA and CsA + D quite similarly led to higher K+ but lower Mg2+ concentrations in plasma. Only with 7 days highest dosage treatment PAH excretion was reduced significantly by CsA and CsA + D treatment. Surprisingly, CsA levels measured in blood and in kidney tissue, showed lower values after co-administration with D compared to CsA treatment alone. This could be caused by higher activities of monooxygenase functions revealed after pretreatment with D alone. Reduced glutathione (GSH) contents in kidney were elevated in CsA and CsA + D treated groups. In general no significant differences were to be observed concerning lipid peroxidation and stimulated H2O2 formation. Altogether evident protective effects of diltiazem on CsA nephrotoxicity in rats could not be proven.

Topics: Animals; Body Weight; Calcium Channel Blockers; Cyclosporine; Cytochrome P-450 Enzyme System; Diltiazem; Drug Interactions; Ethylmorphine; Female; Glomerular Filtration Rate; Glutathione; Immunosuppressive Agents; Kidney; Kidney Diseases; Liver; Organ Size; p-Aminohippuric Acid; Rats; Rats, Wistar

2/3 Hepatectomy (HX), but also sham operation (SO) decreased liver dry mass for the first 3-4 days after operation both in 10- and 60-day-old male Wistar rats, whereas body mass development was not altered. Both SO and HX decreased ethylmorphine N-demethylation (EN) and ethoxycoumarin O-deethylation (EO), but distinctly more pronounced after HX. In 10-day-old rats EN and EO were in the normal range 14 days after SO and HX. After 3 weeks EN even exceeded the control level. In 60-day-old rats SO alone resulted in decreased EN and EO even 3 weeks after operation. Compared with SO-controls EN was lower but EO was in the same range in HX rats 14 days after operation. Neither in 10- nor in 60-day-old rats inducibility by phenobarbital (PB) could be demonstrated 24 h after HX with cytochrome P-450 concentration (P-450), EN and EO as parameters. But inducibility by betanaphthoflavone (BNF) was significant for P-450, EN and EO in 10-day-old rats and also for P-450 and EO in 60-day-old rats. In the young adult rats EN was depressed by BNF. In rats 10 days old at HX inducibility by PB was highest 3-7 days after HX, but inducibility by BNF after 14 days. In 60-day-old rats inducibility by PB was highest for EO 1 day after HX. These results indicate that ontogenetic development can be enhanced by induction, that during development regeneration can be superimposed and both induction and regeneration can superimpose ontogenetic development. During these processes different monooxygenases are under differential control.

Topics: Age Factors; Aging; Animals; Benzoflavones; beta-Naphthoflavone; Body Weight; Coumarins; Cytochrome P-450 Enzyme System; Enzyme Induction; Ethylmorphine; Hepatectomy; Liver; Liver Regeneration; Male; Phenobarbital; Rats; Rats, Inbred Strains

Rats were fed diets resembling a normal human diet, except that, in a complete factorial fashion, safflower oil and/or mineral oil were substituted for part of the fat, while fructose, lactose and/or cellulose were substituted for carbohydrate, and zein was substituted for milk protein. Food intake and weight gain were not influenced by cellulose and mineral oil, but zein decreased both substantially. Plasma cholesterol was unchanged by safflower oil or mineral oil but was decreased by fructose. Plasma glucose was reduced as the starch-to-sugar ratio increased. The rate of aniline metabolism was increased by lactose and/or zein, but the rate of ethylmorphine metabolism was decreased by safflower oil or mineral oil.

Topics: Aniline Compounds; Animal Nutritional Physiological Phenomena; Animals; Biotransformation; Blood Glucose; Body Weight; Cholesterol; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Ethylmorphine; Liver; Rats