diphenylhexatriene and Body-Weight

The present study evaluated the modulatory effects of zinc on colonic membrane fluidity and surface abnormalities following 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis. Rats were segregated into four groups: normal control, DMH treated, zinc treated, DMH + zinc treated. Colon carcinogenesis was initiated through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 weeks. Zinc (in the form of zinc sulphate) was supplemented to rats at a dose level of 227 mg/L in drinking water, ad libitum, for the entire duration of the study. Brush border membranes (BBM) were isolated from the colon of rats and the fluidity parameters were assessed by steady-state fluorescence polarization technique using the membrane extrinsic fluorophore 1,6-diphenyl-1,3,5-hexatriene (DPH). The translational diffusion was measured by using the excimer formation of pyrene incorporated in the membrane. The results demonstrated a significant increase in the polarization and anisotropy, accompanied by an increase in order parameter in the membrane preparations from the colon of DMH-injected rats. Further, studies with pyrene fluorophore indicated a marked decrease in membrane microviscosity following DMH treatment. However, the alterations in membrane fluorescence polarization and the fluidity parameters were completely restored following zinc treatment. Drastic alterations in colon surface were noticed after 8 weeks of DMH treatment. However, zinc treatment to DMH-treated rats greatly restored normalcy in the colonic surface. The study concludes that zinc has a strong membrane stabilizing effect and thus has a positive beneficial effect against chemically induced colonic preneoplastic progression in rats.

Topics: 1,2-Dimethylhydrazine; Animals; Body Weight; Colon; Colonic Neoplasms; Diphenylhexatriene; Fluorescence Polarization; Male; Membrane Fluidity; Microscopy, Electron, Scanning; Microvilli; Pyrenes; Rats; Rats, Wistar; Surface Properties; Viscosity; Zinc

Marked changes in biophysical properties, including structural order, have been observed in the hydrophobic core of cell membranes exposed to phenothiazines in vitro. In this study, similar changes are reported in vivo in cell membranes from the brains of rats treated with phenothiazines at doses thought to yield tissue concentrations approximating those attained in the clinical treatment of psychiatric patients. The membrane structural order parameter was estimated ex vivo by steady-state fluorescence polarization determinations using 1,6-diphenyl 1,3,5-hexatriene (DPH), a fluorescent probe that localizes preferentially to the hydrocarbon region of cell membranes. In these preliminary studies, rats received chlorpromazine (20 mg/kg), fluphenazine (1 mg/kg), haloperidol (1 mg/kg), and imipramine (1 mg/kg) in single or multiple dose protocols. As in earlier in vitro studies, exposure to the phenothiazine antipsychotics led to an observed increase in DPH fluorescence polarization ex vivo and a presumed increase in structural order. As predicted from the in vitro experiments, the effect of chlorpromazine was greater than that of fluphenazine, probably because chlorpromazine was given at higher doses. The magnitude of the effects seen was great enough to imply that physiologically significant changes in cell membrane characteristics may be produced in patients receiving phenothiazines.

Topics: Animals; Antipsychotic Agents; Body Weight; Brain; Cell Membrane; Diphenylhexatriene; Fluorescence Polarization; Imipramine; Male; Phenothiazines; Rats; Rats, Inbred Strains