secalonic-acid and Body-Weight

Topics: Animals; Body Temperature; Body Weight; Creatine Kinase; Dimethyl Sulfoxide; Erythrocyte Count; Hematocrit; Hemoglobins; L-Lactate Dehydrogenase; Leukocyte Count; Male; Mice; Organ Size; Xanthenes; Xanthones

Pregnant mice (dams) were gavaged once on gestational day 13 with 4 ml/kg of dimethylsulfoxide vehicle containing 0 (groups 15, 25 and negative control) or 25 (positive behavioral teratogenic control group) mg/kg of secalonic acid D (SAD). While nursing their offspring, dams were gavaged on postgestational days 1 to 10 with vehicle containing 0 (negative and positive control groups), 15 (group 15) or 25 (group 25) mg/kg/day of SAD. Gestational lengths, maternal pregnancy weights, litter sizes, neonatal sex ratios, neonatal physical appearance and female birth weights were unaffected by prenatal treatment, but male pups born to positive control dams weighed less (p less than 0.05) than negative control group. Compared to negative control, the positive control dams gained significantly more weight while nursing their offspring. Prenatal (positive control) and postnatal (15, 25) SAD exposure delayed ontogeny of surface righting, olfactory discrimination and hindlimb grip behaviors in males and females, and testes descent in males. Negative geotaxis in male and female offspring of group 25 and male offspring of positive control group, as well as times of incisor eruptions of both sexes in groups 15 and 25 were delayed. A significant dose-response effect in olfactory discrimination existed between the groups exposed to postnatal SAD. SAD was behaviorally teratogenic following both prenatal and early postnatal exposure.

Topics: Animals; Animals, Suckling; Behavior, Animal; Body Weight; Female; Gestational Age; Male; Maternal-Fetal Exchange; Mice; Mycotoxins; Pregnancy; Prenatal Exposure Delayed Effects; Sexual Maturation; Teratogens; Xanthenes; Xanthones

Mice were gavage-fed on day 13 of pregnancy with 0 (groups N, 15, 25) or 25 (group P) mg/kg of secalonic acid D (SAD) and again while nursing their offspring on postgestational days 1-10 with 0 (N,P), 15(15) or 25(25) mg/kg/day. SAD residues were present in the stomach of pups nursed by SAD-treated dams. Postnatal exposure to SAD decreased (P less than 0.05) body weight gains of offspring. Treatment decreased the developmental levels of norepinephrine and dopamine in the prosencephalon (forebrain) and cerebellum-pons of the offspring on postnatal days (PND) 7 and 7-16, respectively. On PND 7-16 serotonin and 5-hydroxyindoleacetic acid levels decreased in the prosencephalon and cerebellum-pons of offspring exposed prenatally (P) or postnatally (15,25) to SAD.

Topics: Animals; Animals, Newborn; Animals, Suckling; Biogenic Monoamines; Body Weight; Brain; Catecholamines; Embryonic and Fetal Development; Female; Indoles; Lactation; Mice; Milk; Pregnancy; Xanthenes; Xanthones

Dimethylsulfoxide (DMSO) is known to antagonize the teratogenic effects of secalonic acid D (SAD) in mice. To establish the optimum protective dose of DMSO, pregnant CD-1 mice were treated, i.p., with 30 mg/kg of SAD in 5% (w/v) NaHCO3, containing 0, 10, 20, or 30% (v/v) DMSO on day 11 of gestation. Data indicate that at 10% and 20% levels, DMSO affords an apparent dose-related protection against SAD-induced cleft palate, whereas 30% DMSO enhanced fetal resorption with no reduction in the incidence of cleft palate. Ultraviolet spectra and TLC mobility indicated that DMSO at 20% did not directly interact with SAD. Distribution and elimination of 14C-SAD was studied in fetal and maternal tissues from pregnant mice at 24 and 48 hr after exposure to 30 mg/kg of 14C-SAD, i.p., in NaHCO3 (control) or in 20% DMSO. Compared with those not receiving DMSO, maternal exposure to DMSO: 1) significantly reduced (42-75%) radioactivity in fetal heads and bodies, placenta, and maternal tissues other than liver; 2) significantly increased (up to 222%) the radioactivity in maternal liver; and 3) significantly reduced (44-58%) fecal and urinary elimination of SAD-derived radioactivity. These results suggest that the antiteratogenic effect of DMSO against SAD may be at least partly mediated by increased SAD (or its metabolites) retention by maternal liver leading to reduced SAD uptake by the fetus.

Topics: Animals; Body Weight; Cleft Palate; Dimethyl Sulfoxide; Female; Fetal Resorption; Fetus; Mice; Mycotoxins; Pregnancy; Reference Values; Teratogens; Xanthenes; Xanthones

Toxicity of the mycotoxin secalonic D (SAD) was examined histopathologically in rats. Dose response was studied by intragastric and intratracheal instillation, and SAD was given in suspension in Krebs-Ringer phosphate solution at doses well below the reported LD50 values for both rats and mice. A full autopsy was performed on rats sacrificed 1--69 d after instillation. Responses differed markedly depending on the route of administration. Histopathological lesions were observed only in the lungs of rats receiving SAD intratracheally. At 24 h after treatment, the lungs of affected animals showed an acute polymorphonuclear reaction in the distal airways and adjacent alveoli and there was necrosis of airway epithelium. The latter resulted in the development of typical lesions of bronchiolitis obliterans. The initial acute inflammatory response in the peripheral lung became granulomatous at 3 d and the granulomas contained numerous foreign body type giant cells. Between 3 and 7 d the granulomas and bronchiolitis obliterans increased in severity; thereafter they tended to resolve. On termination of the experiment at 69 d there were a few small residual granulomas; however, no significant irreversible pulmonary injury was observed.

Topics: Animals; Body Weight; Female; Lung; Male; Mycotoxins; Rats; Rats, Inbred Strains; Time Factors; Xanthenes; Xanthones

Teratogenic effects of secalonic acid D (SAD), a toxic fungal metabolite, produced by P. oxalicum has been studied in rats. Crystalline SAD was injected as a single subcutaneous dose (25 mg/kg) on one of the gestation day 6-10, 12 or 14. Pregnant rats were treated with 15 mg/kg SAD on gestation day 10. Both doses produced teratogenic and fetotoxic effects, although the effects produced with the lower dose were less marked. Treatment on days 9 and 10 resulted in increased fetal resorptions and decreased fetal body weights. The highest number of resorptions, greatest depression of fetal body weights and largest number of malformations occurred when SAD was injected on day 10. Anophthalmia (days 9 and 10), exencephaly (day 9) and defects in limbs, digits and tail (day 10) were the major gross malformations. The main internal soft tissue defects were hydronephrosis (days 9 and 10) and tracheo-esophageal fistula and renal agenesis (day 10). Major skeletal defects involved the vertebrae and ribs. For all of the abnormalities observed, administration of SAD on day 10 of gestation produced the most marked effects in rats.

Topics: Abnormalities, Drug-Induced; Animals; Body Weight; Embryo Implantation; Female; Fetal Resorption; Fetus; Gestational Age; Mycotoxins; Pregnancy; Rats; Teratogens; Xanthenes; Xanthones

Toxicity of secalonic acid D was examined by using lethality, growth retardation, and histopathology as indexes. The ip LD50 values of 37, 31, and 27 mg/kg were obtained for Charles River CD-1, Texas (ICR), and Sprague-Dawley (CF-1) strains of mice, respectively. The ip LD50 was 52 mg/kg in female CD-1 mice. The iv LD50 was 25 mg/kg in CD-1 male mice. Oral LD50 values of 400 mg/kg in male CD-1 mice and 25 and greater than 400 mg/kg in Sprague-Dawley day-old and weanling (21 d) rats of both sexes, respectively, were obtained. Doses of 20 mg/kg or more ip retarded growth and doses of 30 mg/kg or more ip were lethal to CD-1 mice. Oral doses required to produce such effects in day-old rats were 5 and 20 mg/kg (or higher), respectively. All ip doses of secalonic acid D caused pulmonary atelectases and foccal peritonitis in male CD-1 mice. The latter involved surfaces of abdominal viscera and produced limited subcapsular necrosis of hepatic parenchyma. Exposure to a single lethal dose iv (25 mg/kg or more) of secalonic acid D caused limited hepatic portal necrosis but no peritonitis or other associated local effects observed in CD-1 male mice after ip exposure. Cytoplasmic liposis and loss of glycogen and RNA from hepatocytes were observed in a single mouse receiving 50 mg/kg iv. Death resulting from cardiac and/or pulmonary insufficiency was suggested by atelectasis, pulmonary hemorrhages and edema, and massive atrial dilation in mice that died after lethal ip or iv doses of secalonic acid D. Five daily sublethal ip doses in CD-1 male mice resulted in dose-dependent mortality (LD50, 11.5 mg/kg) indicating cumulative effects.

Topics: Animals; Body Weight; Carboxylic Acids; Female; Lethal Dose 50; Lung; Male; Mice; Mycotoxins; Rats; Species Specificity; Time Factors; Xanthenes; Xanthones