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Biomedical subjects

D S Sachan

Publications and source records attributed to D S Sachan.

At least 37 records · Page 2Linked to original sources
PubMed1984

Ameliorating effects of carnitine and its precursors on alcohol-induced fatty liver.

The lipid-lowering effect of carnitine and its precursors, namely lysine plus methionine, was examined in male Sprague-Dawley rats fed ethanol as 36% of the total calories. Ethanol caused typical hepatic steatosis characterized by significant accumulation of total lipids, triglycerides, cholesterols, phospholipids, and free fatty acids. Supplementation of the ethanol diet with 1% DL-carnitine, 0.5% L-lysine, and 0.2% L-methionine significantly lowered ethanol-induced increases of various lipid fractions, with the exception of free fatty acids. The lipid-lowering effect of carnitine was superior to that of its precursors and their effect together was no greater than that of carnitine alone. The triglyceride contents of liver and plasma were related inversely to the levels of carnitine and acyl carnitines. It is concluded that dietary carnitine more effectively than its precursors prevented alcohol-induced hyperlipemia and accumulation of fat in livers. Thus, a deficiency of functional carnitine may indeed exist in chronic alcoholic cases.

Animals↗
PubMed1982

Alterations of NADPH-generating and drug-metabolizing enzymes by feed restriction in male rats.

Two groups of weanling male Sprague-Dawley rats were fed a semisynthetic diet (ad libitum group) and 50% of that consumed by the ad libitum group (restricted group) for 49 days. Compared to the ad libitum group, the animals of the restricted group gained 55% less in body weight and had 60% smaller livers. While serum glucose, urea nitrogen, uric acid and lipids were lowered in the restricted animals, other serum biochemical parameters remained unchanged. The in vitro activities of hepatic drug-metabolizing enzymes were increased two- to threefold in the restricted animals. Feed restriction also caused a significant increase in the activities of NADPH-generating enzymes of liver and adipose tissue; however, the enzymes not concerned with the production of NADPH remained unaffected by feed restriction. It is concluded that feed restriction, unlike starvation, enhanced activities of drug-metabolizing enzymes as well as NADPH-generating enzymes.

Adipose Tissue↗
PubMed1980

Carnitine biosynthesis. Hydroxylation of N6-trimethyl-lysine to 3-hydroxy-N6-trimethyl-lysine.

Rat kidney homogenates metabolize N6-trimethyl-lysine to N-trimethylammoniobutyrate, but not to carnitine. The first step in this conversion is the hydroxylation of trimethyl-lysine to form 3-hydroxy-N6-trimethyl-lysine. An assay system was developed in which hydroxylation of trimethyl-lysine is linear with respect to both time and homogenate protein concentration. The rate is 5 nmol of 3-hydroxy-N6-trimethyl-lysine formed/min per mg of homogenate protein. The cofactors required are ascorbate, alpha-oxoglutarate, FeSO4, and O2. Catalase and dithiothreitol give a 20% stimulation. Ca2+ produces a 2-fold increase in specific activity and cannot be replaced by Mg2+, Mn2+ or Zn2+. These last three bivalent cations lead to a decreased activity. Subcellular distribution studies demonstrate that trimethyl-lysine hydroxylase activity parallels the distribution profile of succinate dehydrogenase and citrate synthase. Thus trimethyl-lysine hydroxylase has a mitochondrial localization. Distribution of trimethyl-lysine hydroxylase activity between cortex and medulla of kidney if 67 and 33% respectively, similar to mitochondrial distribution.

Animals↗
PubMed1976

Induction of microsomal drug metabolizing enzymes by oral contraceptives in protein-malnourished rats.

In order to examine effects of oral contraceptives (OC) on the microsomal drug matabolizing enzymes in a state of protein malnutrition, weanling Sprague-Dwayley female rats were fed diets containing 3.5% (low protein, LP), 26% (normal protein, NP) or 42% (high protein, HP) casein for 224 days and norethynodrel plus mestranol for the last 182 days. LP rats were smaller in body weight than NP and HP rats and the latter two groups showed depressed weight gain and hypertrophy of liver and kidney due to OC. Concentrations of microsomal proteins and cytochrome P-450 were lowered by LP diet and OC did not induce cytochrome P-450. Activity of biphenyl-4-hydroxylase was lowered in LP and HP rats compared to NP group in which activity of this enzyme was significantly decreased due to OC. The diets alone had no effect on the activity of p-nitrobenzoate reductase, however, its activity was enhanced by OC only in NP rats. LP diet caused reduction of 4-methylumbelliferone glucuronly transferase activity which was lowered by OC in NP as well as in LP rats. It is concluded that NP diet more than either LP or HP diet exposed rats to the modification of microsomal drug metabolizing enzymes by OC.

Animals↗
PubMed1975

Effects of low and high protein diets on the induction of microsomal drug-metabolizing enzymes in rat liver.

To determine the effect of low and high levels of dietary proteins plus low doses of phenobarbital (PB) on the induction of drug-metabolizing enzymes, weanling male and female Sprague-Dawley rats were fed, ad libitum, diets containing 3.5 (low protein, LP), 26 (normal protein, NP), and 42% (high protein, HP) casein for 33 days. Five animals from each dietary group were injected with 10 mg of PB/kg body weight, intraperitoneally, for the last 3 days of the experimental period. The 10,000 X g supernatant and microsomes were prepared from perfused livers from each group. Both LP and HP diets caused a significant decrease in the activity of biphenyl 4-hydroxylase, an increase in the activity of p-nitrobenzoate reductase, and no changes in the activities of 4-methylumbelliferone glucuronyltransferase and cytochrome P-450. The low doses of PB used in this study caused significant induction of cytochrome P-450 (P less than 0.10), biphenyl 4-hydroxylase, and p-nitrobenzoate reductase (except in LP and NP females). The males of NP and HP groups had consistently higher activities of these enzymes than corresponding females, however, this sex difference in the first two enzymes was abolished by feeding of the LP diet.

Animals↗
PubMedDate not supplied

Attenuation of ethanol metabolism by supplementary carnitine in rats.

The purpose of this study was to examine the effect of supplementary D,L-carnitine on blood-ethanol levels and ascertain if the effect was a result of altered absorption or metabolism of ethanol. Mature male Sprague-Dawley rats were fed Purina Rat Chow as such or supplemented with various levels of D,L-carnitine. First it was established that supplementing carnitine at 1% (w/w) level produced steady state concentrations of carnitine in blood after 3 days of feeding. When a single dose of ethanol was given orally after 5 days of carnitine supplementation, the blood levels of ethanol remained significantly elevated for 2-8 hours in the carnitine supplemented animals. Time course of blood-ethanol concentrations revealed that carnitine did not affect the rates of ethanol absorption and therefore, the effect must be due to the attenuation of ethanol clearance from the blood.

Animals↗
PubMedDate not supplied

Acetylcarnitine-mediated inhibition of ethanol oxidation in hepatocytes.

Carnitine-mediated prevention of ethanol-induced hepatic steatosis is related to the attenuation of ethanol metabolism by carnitine in the intact rat. Although carnitine retards ethanol oxidation in the intact animal, the in vitro activities of ethanol-metabolizing enzymes remain unaltered. Therefore, hepatocytes were targeted to understand the mechanism of carnitine effect on ethanol metabolism. Rat hepatocytes were isolated by a collagenase-perfusion technique and incubated in albumin-containing medium with ethanol in the presence or absence of added carnitine or related compounds. Ethanol oxidation was determined by the loss of ethanol as well as by the products formed. The rate of ethanol oxidation in the presence of carnitine was one-half the rate in the absence of carnitine (14 vs. 25 nmol.min-1.million-1 cells). It took 100 times the concentration of carnitine to equal the maximal inhibition produced by acetylcarnitine and the effect of acetylcarnitine was without a lag time. It is concluded that acetylcarnitine is the mediator of carnitine inhibition of ethanol oxidation.

Acetylcarnitine↗
PubMedDate not supplied

Plasma carnitine alterations in premature infants receiving various nutritional regimes.

Plasma carnitine, carnitine esters, and triglyceride concentrations were determined in 36 appropriate-forgestational-age (AGA) infants at various stages of prematurity throughout hospitalization to determine the effect of a carnitine-free and carnitine-containing diet on plasma carnitine and triglyceride concentrations. The infants were entered into one of three experimental groups based on birth weight: group I less than 1.0 kg; group II 1.0-1.51 kg; and group III 1.52-2.5 kg. Throughout the study subjects were placed on appropriate nutritional regimes which included hyperalimentation (HA), intravenous (iv) fat emulsion (Intralipid), Portagen, Enfamil-24 Premature Formula, Enfamil-20, and breastmilk. Blood samples were drawn from each infant at birth, days 1-5,7 then weekly, also before and after each nutritional intervention to determine carnitine and triglyceride concentrations. Results showed that plasma total carnitine and nonesterified carnitine decreased in all groups when the infants were maintained on a carnitine-free diet (HA, Intralipid, Portagen). In general, the carnitine levels continued to decrease until a carnitine-containing diet was initiated. Once a carnitine-containing diet was begun, plasma total carnitine (TC) and nonesterified carnitine (NEC) levels increased at fairly similar rates in all groups. However, an inverse relationship between carnitine and triglyceride (TG) concentrations were not seen in these infants. This would indicate that most premature infants require exogenous carnitine to maintain the plasma concentration of carnitine. However, a decreased concentration of plasma carnitine was not correlated with an elevated TG level under the conditions of this study.

Carnitine↗
PubMedDate not supplied

Suppression of aflatoxin B1-induced lipid abnormalities and macromolecule-adduct formation by L-carnitine.

The fatty liver and hypolipidemia caused by aflatoxin B1 (AFB1) were studied in male Sprague-Dawley rats fed Purina Rat Chow with or without L-carnitine supplement for 6 weeks. In Experiment 1, the rats (n = 20) were divided into four groups, i.e., nonsupplemented control (NSC), nonsupplemented AFB1 (NSA), carnitine supplemented control (CSC), and carnitine supplemented AFB1 (CSA). The NSA and CSA groups were given an oral dose of [3H]AFB1 (1 mg/kg) 6 hr before kill. In Experiment 2 (n = 10) there were only NSA and CSA groups and they were killed 24 hr post-AFB1 administration. Hepatic and plasma concentrations of total lipid, triglycerides, AFB1-macromolecules adducts and urinary excretion of AFB1 were determined. Carnitine supplementation ameliorated AFB1-induced hepatic steatosis and hypolipidemia. Supplementary carnitine reduced covalent binding of AFB1 to hepatic DNA, RNA, and protein. The carnitine effect was more pronounced after 24 hr than after 6 hr of AFB1 treatment. We conclude that supplementary carnitine suppressed AFB1-induced fatty liver and AFB1-macromolecule adduct formation in the rat.

Aflatoxin B1↗
PubMedDate not supplied

Effects of L-carnitine on carbon tetrachloride-induced changes in serum and liver lipids and acylcarnitines.

Effects of 0.5% L-carnitine-supplemented diet on carbon tetrachloride-induced alterations of hepatic and serum lipids were examined in male rats. Treatment with carbon tetrachloride significantly increased hepatic total lipids, triglycerides, and total carnitine, but these were not significantly altered by 0.5% L-carnitine supplementation. However, in plasma, supplementary carnitine significantly decreased nonesterified fatty acids and increased acylcarnitines. These suggest that carnitine may soften hepatic lipid load by releasing acylcarnitines in blood.

Animals↗