Biomedical subjects

T G Vitti

Publications and source records attributed to T G Vitti.

12 recordsLinked to original sources

PubMed1997

Pharmacokinetics of ochratoxin A and its metabolites in rats.

Ochratoxin A (OA) is a mycotoxin that is produced on moist grain. It is commonly found in the blood of swine in western Canada and is a potent nephrotoxic, carcinogen, and immunosuppressive agent. The pharmacokinetic characteristics of six analogs of OA including OA, OB (OA without chloride), OC (OA ethyl ester), and some metabolites, such as O alpha (OA without phenylalanine), OA-OH (hydroxylated OA), and a newly discovered form of OA, OP-OA (lactone opened ring of OA), were investigated in rats after a single intravenous administration of the compounds. All of the ochratoxin analogs were distributed following a two compartment open model. The elimination half-lives of OA, OP-OA, O alpha, OA-OH, OB, and OC were 103+/-16, 50.5+/-2.8, 9.6+/-2.3, 6+/-0.9, 4.2+/-1.2, and 0.6+/-0.2 hr, respectively. Total body clearance of OA, OP-OA, O alpha, OA-OH, and OB via the bile, urine, and metabolic routes were 3.1, 3.6, 40, 65, and 43 ml/hr kg, respectively. OA, OB, and O alpha were mainly cleared in the urine (> or = 48%), OA-OH in the bile (41%), and OP-OA as metabolites (43%). Metabolism accounted for 43, 44, 33, and 29% of the total clearance of OA, O alpha, OA-OH, and OB, respectively. It is concluded that OA has a long half-life and is very slowly cleared from the body and that its metabolites are cleared at a much faster rate with much shorter half-lives. Procedures should be devised to enhance the conversion in the body of OA to O alpha, OA-OH, or other metabolites as this would shorten its half-life and therefore its toxicity.

Animals↗

PubMed1991

Effect of a hay and a grain diet on the rate of hydrolysis of ochratoxin A in the rumen of sheep.

The hydrolysis of ochratoxin A (OA) and the corresponding formation of its hydrolysis product, alpha ochratoxin (O alpha), by ruminal digesta and in the rumen of hay-fed and grain-fed sheep were compared. Ruminal contents from sheep fed diets with hay or with grain hydrolyzed OA in vitro; the majority of the activity was associated with the particulate fraction of the ruminal contents. The rate of hydrolysis of OA by ruminal fluid that was adjusted to different pH values was not influenced (P greater than .6) by the pH of the samples (pH was from 5.5 to 7.0). Ruminal fluid obtained from hay-fed animals (pH 7.0) was able to hydrolyze OA in vitro and to produce the hydrolyzed product, O alpha, at a much greater rate (fivefold) than ruminal fluid obtained from grain-fed animals (pH 5.5) (P less than .01). Ochratoxin A was administered intraruminally at a concentration of .5 mg/kg of BW to hay-fed and grain-fed sheep. The half-lives for disappearance of OA from the rumen of sheep fed grain (normal feed intake, rumen pH 5.7), fed grain at a low level (30% of normal feed intake, pH 6.5), and fed hay (pH 7.1) were 3.6, 1.3, and .6 h, respectively. The results suggest that OA is hydrolyzed much faster in the rumen of sheep fed hay than in sheep fed grain, presumably because of the different ruminal microbial population, which in turn influenced the rate of hydrolysis of OA.

Animal Feed↗

PubMed1991

Effect of a hay and a grain diet on the bioavailability of ochratoxin A in the rumen of sheep.

The role of the rumen and its contents in the detoxification of ochratoxin A (OA) was studied in sheep. The first experiment established that very little conversion of OA to alpha ochratoxin (O alpha) occurs systematically; 90 to 97% of the OA and metabolites was recovered as unaltered OA in the urine. Most of the small amount of O alpha recovered was also in the urine. In this experiment, two sheep were fasted and another two fed normally, but feed intake had no significant effect. In the second experiment, two sheep fed hay and two fed grain were dosed with OA at .5 mg/kg of BW into the rumen via a cannula. Recoveries, in urine and feces, accounted for 58 to 70% of the administered OA, but almost all (greater than 97%) was in the form of O alpha. About 76 to 92% of this O alpha was in the urine. Although excretion patterns and pharmacodynamics tended to differ with different diets, one of the sheep fed grain had very low intake and the results were equivocal. In the third experiment, eight sheep (four fed hay, four fed grain) were given a single intraruminal dose of OA (.5 mg/kg of BW). The disappearance of OA from the rumen and the corresponding formation of O alpha was much faster for hay-fed than for grain-fed sheep; the half-lives were .63 and 2.7 h for OA and .9 and 1.9 h for O alpha, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

PubMed1988

Studies of the tolerance and disposition of ochratoxin A in young calves.

Tolerance to and disposition of ochratoxin A (OA) were compared in preruminant and ruminant calves. Two preruminant calves receiving 4.0 mg OA/kg body weight by stomach tube died; one of two calves receiving 1.0 mg/kg body weight survived. At a dose of .5 mg OA/kg body weight both calves survived. The administered OA was converted mainly (80.1 to 88.9%) to ochratoxin-alpha (O alpha), which was found only in urine; the remaining OA appeared in the urine (3.2 to 3.3%) and feces (7.8 to 10.0%). In the one surviving calf of two given .25 mg OA/kg body weight i.v., nearly twice as much OA was excreted in the feces (44.5%) as in the urine (25.0%); no O alpha was found in urine or feces. All four calves with functional rumens receiving OA orally, 2.0 mg/kg body weight, survived without overt ill effects. Approximately 90% of the OA was excreted as O alpha, with approximately four to eight times more in the urine than in the feces; OA was low in the urine or feces. A plot of the serum OA concentration-time data revealed a prominent, sustained, secondary peak, which was described adequately by a four-exponential equation with two apparent absorption components. Accordingly, OA initially was absorbed rapidly by a first-order rate process (ka = .496/h), and following a considerable delay (tlag = 12.84 h) absorption appeared to resume by a second, slower, first-order rate process (ka = .127/h). The second absorption phase was best explained as being due to enterohepatic cycling of OA.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1986

Effect of Erythroxylum coca, cocaine and ecgonine methyl ester as dietary supplements on energy metabolism in the rat.

The effects of dietary supplements of cocaine, ecgonine methyl ester, a coca leaf extract and powdered coca leaves on body weight and overall body metabolism were studied in the rat. Respiratory quotient was measured to assess the relative utilization of fats, carbohydrates and protein. The effect of cocaine and ecgonine methyl ester on protein metabolism was also assessed in terms of changes in the relative state of nitrogen balance. Rats maintained on a low protein/high carbohydrate diet containing cocaine (1 mg/g) exhibited normal body weight gain on normal food intake. Rats on the same diet with 2 mg/g cocaine as the hydrochloride or as coca dextrin lost weight, which was apparently related to diminished food intake. In contrast, rats received the same high level of cocaine as coca leaf powder in the same diet had minimal weight gain in spite of a high food intake. In contrast, rats receiving the same high level of cocaine as ly, rats receiving the same high level of cocaine (2 mg/g) in a high protein diet had normal food intake and body weight gain. An adequate protein diet appears to compensate for whatever inhibiting effect is imposed on the body by the high levels of cocaine. Ecgonine methyl ester appears to have no significant effect on food intake or body weight. Rats fed the low protein/high carbohydrate diet containing either the low (1 mg/g) or the high (2 mg/g) cocaine level exhibited significantly depressed respiratory quotients (near 0.75) suggesting increased fat utilization. The magnitude of the reduction appeared to be dose-related. Yet, the respiratory quotient of the rats receiving the high level of cocaine in a high protein diet remained at normal control values. Also, in a separate nitrogen balance-type of experiment, rats receiving the low level of cocaine (1 mg/g low protein/high carbohydrate diet) exhibited a normal ability to accumulate body nitrogen, presumably protein. These results support the idea that under conditions of protein deprivation cocaine helps spare amino acids through the preferential utilization of fat. Coca leaf in the low protein/high carbohydrate diet equivalent to 2 mg/g cocaine had a small but significant positive effect on respiratory quotient possibly due to the availability of utilizable nitrogenous components in the coca leaf. The respiratory quotient effects were less obvious with an extract of coca leaf incorporated in the diet as coca-dextrin, but showed the same trend.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1976