retrorsine and Body-Weight

The effect of three dietary concentrations of Crotalaria pallida (C. pallida) seeds (0, 1, 2, and 3% w/w) of their normal diet were investigated in commercial laying hens during a 35 day feeding trial. All concentrations of C. pallida decreased body weight and feed intake (P < 0.05). Egg mass production and average egg weight were decreased by feeding of ≥ 2% C. pallida seeds (P < 0.05). All concentrations of C. pallida increased relative lung weight and serum activity of ALT, AST and LDH (P < 0.05); 3% C. pallida seeds decreased liver weight (P < 0.05). Analysis of the C. pallida seeds for dehydropyrrolizidine alkaloid content detected usaramine and its N-oxide at a total alkaloid concentration of 0.18% (dry weight). Usaramine was also detected in the eggs of all hens fed C. pallida seeds.

Topics: Animal Feed; Animals; Behavior, Animal; Body Weight; Chickens; Crotalaria; Diet; Eating; Eggs; Female; Food Contamination; Liver; Plant Extracts; Pyrrolizidine Alkaloids; Seeds

To explore the hypothesis that a second xenobiotic agent is required with excess copper to produce Indian Childhood Cirrhosis, this study investigated the effect of the pyrrolizidine alkaloid retrorsine fed to the mother during the suckling period upon the serial changes in neonatal copper status.. Female Wistar rats with new-born litters were fed either a control or a retrorsine (50 mg/kg) diet. At 0, 4, 8, 11, 15, 18 and 21 days, pups from each litter were weighed, sacrificed and their livers removed for copper, DNA and metallothionein analysis. Serum samples were assayed for caeruloplasmin oxidase activity and albumin.. 1) Higher than adult level of hepatic copper in normal rats which rose post-natally before declining from day 11 after birth, 2) raised hepatic copper concentrations and total copper in the retrorsine group from day 15; levels were higher than adult at birth, 3) reduced serum caeruloplasmin oxidase activity and albumin levels in retrorsine group, but both groups lower than adult, 4) lower hepatic metallothionein levels in retrorsine group, but both groups higher than adult, and 5) reduced liver DNA in the retrorsine group when expressed as total DNA and per gram of tissue. These changes were not secondary to under-nutrition as a small study on under-nourished rat neonates showed that copper handling is not significantly altered when compared to well-nourished rats.. Retrorsine passing to rat neonates via breast milk causes: 1) the accumulation of hepatic copper, 2) impairment of the rise in serum caeruloplasmin, which could indicate a decline in synthesis or failure of copper incorporation into the apo-protein, 3) a decrease in hepatic metallothionein and serum albumin levels, again suggesting diminished protein synthesis, and 4) reduced hepatic DNA indicative of decreased cell number but increased cell size. Accumulation of liver copper but reduction of copper-binding proteins could result in free copper and explain the synergistic hepatotoxicity of copper and retrorsine.

Topics: Animals; Animals, Suckling; Body Weight; Ceruloplasmin; Chemical and Drug Induced Liver Injury; Copper; DNA; Drug Evaluation, Preclinical; Female; Liver; Liver Diseases; Metallothionein; Milk; Nutrition Disorders; Organ Size; Pyrrolizidine Alkaloids; Rats; Rats, Wistar; Serum Albumin

To investigate the possible synergy between copper and retrorsine (a pyrrolizidine alkaloid) as a cause of Indian Childhood Cirrhosis, four groups of male Wistar rats were fed the following diets from weaning: A. Normal diet; B. Copper loaded (2 g CuSO4/kg diet); C. Retrorsine supplemented (Expt 1:25 mg/kg body weight/week by gavage, Expt 2:25 mg/kg food initially then 15 mg/kg food after 4 weeks); and D. Copper and retrorsine as above. Serial plasma samples were assayed for aminotransferases, albumin and bilirubin. Liver samples at biopsy and sacrifice provided samples for copper analysis and histology. Results showed that copper and retrorsine together significantly increased liver damage compared with feeding either alone as assessed by: 1. Increased mortality rate; 2. Decreased plasma albumin and increased plasma bilirubin (mainly conjugated) indicative of hepatocyte dysfunction; 3. Massive liver copper accumulation, and 4. Increased liver damage histologically. Thus retrorsine caused liver copper accumulation, and together copper and retrorsine led to severe hepatic dysfunction, characterised by hypoalbuminaemia and conjugated hyperbilirubinaemia. Plant alkaloids secreted in milk by grazing animals and copper from brass vessels may together produce Indian Childhood Cirrhosis.

Topics: Animals; Body Weight; Copper; Drug Synergism; Liver; Liver Function Tests; Male; Osmolar Concentration; Pyrrolizidine Alkaloids; Rats; Rats, Wistar; Survival Analysis