Effect of adrenocorticotrophic hormone on the activity of sterol ester hydrolase from rat brain

Adrenocorticotrophic hormone (ACTH) stimulates in vitro the hydrolysis of oleoylcholesterol by a sterol ester hydrolase from rat brain synaptosomes. The stimulatory effect involves an alkaline shift of the pH optimum of catalysis and culminates at pH 6 with a 15 to 20-fold increase in lipolytic rates. The effect requires trace amount of organic solvent in the substrate emulsion and is dependent on the NH₂-terminal sequence extending through the basic amino acid residues at positions 15–18. The hormonal stimulation is decreased when a lipid-depleted preparation is used as enzyme source, and fully restored upon addition of lecithin. The results raise the possibility that ACTH may have a neuro-hormonal role in brain via modulation of local lipolytic processes.     

Effect of high dose alpha-tocopherol and alpha-tocopherol acetate pretreatment on adriamycin (doxorubicin) induced toxicity and tissue distribution

When two doses (15 mg/kg) of adriamycin (ADM) were administered to ICR mice pretreated with 500 mg/kg/day of alpha-tocopherol (VE) and alpha-tocopherol acetate (VE-AC) respectively, both the VE and the VE-AC pretreatment groups showed a significant shortening of survival time compared to control group. The concentration of ADM and of total aglycone (AD-NE) was determined in the tissue of mice given a single dose of 15 mg/kg of ADM after pretreatment with 500 mg/kg of VE and VE-AC, respectively, high values were found in liver, kidney and heart tissue compared to the control group. And, particularly the heart tissue of the group pretreated with VE showed significantly higher values of ADM and AD-NE. High AD-NE levels were noted in mouse liver mitochondria (Mt), after pretreatment with both VE and VE-AC, with a significantly higher concentration in the VE-pretreated group. A comparison of the uptake of ADM and AD-NE into mouse Mt pretreated with VE or VE-AC in vitro, showed no difference in the ADM value from that of the control group, but both the VE- and the VE-AC-pretreated groups had significantly higher in AD-NE concentrations compared to the control group.     

Effect of body temperature on acute ethanol toxicity

We studied the effect of elevated rectal temperature on ethanol toxicity and the effect of ethanol on the mean lethal temperature (LT50). The rectal temperature was maintained at a preselected level for 4 h. Ethanol (23% w/v) was injected i.p. In control mice anesthetized with pentobarbital, the 4 h LT50 was 41.8 ± 0.1°C (mean ± standard error). In mice which had received a non-lethal ethanol dose (6 g/kg), the LT50 was decreased to 39.0 ± 0.2°C (p< 0.001). In control mice, whose temperature dropped, the 4 h ethanol LD50 was 8.5 ± 0.8 g/kg. If the rectal temperature of the mice was maintained instead at a maximum of 38.5 – 40°C, the LD50 was decreased to 5.7 ± 0.8 g/kg (p < 0.02). The results show that ethanol increases the susceptibility of mice to hyperthermic damage, and conversely, that hyperthermia increases the toxicity of ethanol.