The effect of dietary zinc on induction of cytochrome p-450 by phenobarbital or 3-methylcholanthrene in male Sprague-Dawley rats

The effects of dietary (oral) zinc, as zinc chloride, on the hepatic microsomal monooxygenase system in Sprague-Dawley rats was investigated in the present study. Three routes of zinc administration—oral gavage, intraperitoneal injection and dietary supplement—were compared for accumulation of zinc in the liver and intestine, and induction of hepatic metallothionein (MT). Ip injection was the most effective method for the elevation of tissue zinc levels. Tissue metal and hepatic MT levels did not differ with dietary Zn supplementations. The oral gavage was effective in elevating tissue zinc and hepatic MT levels. Since dietary zinc did not elevate tissue metal content, the oral gavage was used as “dietary” zinc treatment. When zinc was administered orally in a linear fashion (0-200mg/kg), hepatic MT was elevated in relation to the dose size with 200mg/kg Zn⁺² resulting in a 7-fold increase. There was an increase in hepatic microsomal enzymes at 25mg and 50mg Zn⁺² then a decrease with the 100mg and 200mg doses. This could indicate a stabilization-destabilization of the cell membrane. A one day oral dosing scheme was as effective as a 2 or 3 day schedule in the elevation of tissue zinc and hepatic MT levels, but with a decrease in hepatic MT levels at day 3. Oral zinc at 40mg/kg had no effect on level of induction of cytochromes P-450 or b₅ by phenobarbital or 3-methylcholanthrene. Hepatic microsomes isolated from rats that received 40mg Zn⁺² were as effective in the biotransformation of aniline, aminopyrine, or p-nitroanisole as hepatic microsomes isolated from untreated animals. The K_m of aniline of the zinc treated rats was slightly higher than the control. The <i>invitro</i> addition ZnCl₂ (0, 25, 50, 100, 1000μM) to a microsomal reaction mixture resulted in a decrease in the metabolism/biotransformation of aniline, aminopyrine and p-nitroanisole, with p-nitroanisole being the most sensitive. This series of experiments indicated that if zinc was given as an oral supplement, the body is protected from a toxic effect by hepatic and probably intestinal MT. MT binds the excess zinc, and then either delivers it as necessary or holds for elimination from the body. If the protective function of MT is bypassed by intraperitoneal injection or intravenous infusion, zinc could possibly have metabolic consequences. Further studies investigating IV zinc on hepatic drug metabolism are indicated.

Name thesis:degree_name

M.S.

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Human Nutrition and Foods

Department dc:contributor.department

Human Nutrition and Foods

Grantor dc:publisher

Virginia Polytechnic Institute and State University

Year dc:date.issued

1986

Author dc:creator

• O'Conner, Laurel E.

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10919/101141

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/101141