bisdehydrodoisynolic-acid and Disease-Models--Animal

Several lines of research suggest that estrogens (and estrogenic compounds) are neuroprotective following experimental traumatic brain injury. However, therapeutic use of estrogens in this and other regards remains controversial. Therefore, analysis of estrogen-like compounds without potential problems similar to estrogens seems warranted. (±) Z-Bisdehydrodoisynolic acid (Z-BDDA) is a seco-steroid that has potent estrogenic as well as antioxidant activities in vitro and in vivo. We evaluated the therapeutic potential of Z-BDDA (300μg/0.1cc/100g body weight, sc) to promote the recovery of behavioral function following lateral fluid percussion injury (FPI) to the brain in male rats. Two hours subsequent to FPI, treatment with Z-BDDA began with a bolus subcutaneous (sc) injection followed by booster treatments given 24 and 48h later. Behavioral testing was initiated on the second day after FPI and results of Z-BDDA treatments were compared to treatment with vehicle only and to sham FPI surgery. Z-BDDA effectively enhanced recovery of coordinated limb movement assessed by locomotor placing performance across the duration of the study. Z-BDDA treated animals also performed better on a spatial memory task in the Morris water maze, showing improved learning curves across days of testing. Vestibulomotor function, measured by beam walk performance, appeared to improve in Z-BDDA treated animals, however these results did not reach statistical significance (p>0.05). Following cessation of the behavioral testing, all animals underwent assessments of gross neuroanatomical pathology. Cortical lesion size and cell death analysis with Fluoro-jade B failed to reveal Z-BDDA enhanced neuroprotection. These findings support our hypothesis that Z-BDDA can facilitate behavioral recovery following FPI in adult male rats although the mechanism(s) of these effects remain to be determined.

Topics: Animals; Brain Injuries; Disease Models, Animal; Estrogens; Male; Phenanthrenes; Rats; Rats, Long-Evans; Recovery of Function; Secosteroids

The putative selective estrogen receptor modulator (+)-Z-bisdehydrodoisynolic acid (Z-BDDA) has been found to improve cardiovascular risk in rodents. The objective of this study was to investigate the effectiveness of (+)-Z-BDDA compared with the antidiabetic drug, rosiglitazone, in treating obesity and risk factors associated with the metabolic syndrome.. Female Zucker Diabetic Fatty rats were randomly assigned to three treatment groups for 29 weeks: control (C), 1.8 mg (+)-Z-BDDA/kg diet [control diet + (+)-Z-BDDA (CB)], or 100 mg rosiglitazone/kg diet [control diet + rosiglitazone (CR)]. At sacrifice, physiological, biochemical, and molecular parameters were examined.. CB animals gained less weight and exhibited a decrease in total body lipids (p < 0.05) as compared with C or CR rats. Body weight and total body lipids were the highest in CR rats (p < 0.05). Liver weights in CB and CR rats were lower (p < 0.05) than in C rats, whereas kidney weights were lower in CB (p < 0.05) than in C and CR animals. Fasting plasma glucose was lower (p < 0.05) in the CB and CR animals when compared with C animals. C rats exhibited the highest concentration of total plasma cholesterol, and CR-treated rats exhibited the lowest concentration. Plasma triglycerides followed the same pattern as plasma cholesterol. Histomorphometry of heart vasculature revealed that CB and CR treatments produced a significant shift from small to large venules and arterioles compared with C (p < 0.05). Liver expression profiles of peroxisome proliferator-activated receptor (PPAR) alpha, PPARgamma, and PPAR-regulated genes revealed encouraging CB-induced effects.. These results suggest that (+)-Z-BDDA may have applications in treating obesity and complications associated with the metabolic syndrome.

Topics: Animals; Blood Glucose; Body Weight; Cholesterol; Coronary Vessels; Diabetes Mellitus, Experimental; Disease Models, Animal; Female; Gene Expression; Hypoglycemic Agents; Kidney; Liver; Metabolic Syndrome; Obesity; Organ Size; Phenanthrenes; PPAR alpha; PPAR gamma; Random Allocation; Rats; Rats, Zucker; Risk Factors; Rosiglitazone; Selective Estrogen Receptor Modulators; Thiazolidinediones; Triglycerides