Effect of probucol on the cytological and biochemical changes induced by adriamycin in Swiss albino mice.
Probucol [(4,4'-(-(isopropylidenedithio) bis (2,6-di-t-butylphenol)], a hypolipidemic drug, was evaluated for its effects on the clastogenic activity of ADM in Swiss albino mice. Male mice were treated i.p. with different doses (25, 50 and 100 mg/kg, body weight/day) of probucol for 7 days. Some of the mice in each dose group of probucol and those in the positive control group were injected i.p. with Adriamycin (ADM, 8 mg/kg, body weight) and killed after 24 hr. Femoral cells of mice were collected and studied for the frequency of micronuclei and the ratio of polychromatic erythrocytes to Normochromatic erythrocytes. Furthermore, proteins, DNA, RNA, Malondialdehyde (MDA) and non-protein sulfhydryl (NP-SH) levels were determined in the hepatic cells. Probucol treatment failed to induce any significant clastogenic, cytotoxic and biochemical changes. However, pre-treatment with probucol was found to reduce the ADM-induced micronuclei without any alteration in its cytotoxicity. The DNA, RNA, proteins and NP-SH levels in the hepatic cells of these animals were increased and the MDA concentrations were reduced. The inhibition of ADM-induced clastogenicity by probucol may be attributed to its lipids lowering, iron chelating, free radical scavenging and topoisomerase-II-depleting action.
al-Gharably
N M
NM
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D004347:Drug Interactions; D004912:Erythrocytes / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D011341:Probucol / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D000924:Anticholesteremic Agents; D009153:Mutagens; D011506:Proteins; D008315:Malondialdehyde; D012313:RNA; D004317:Doxorubicin; D004247:DNA; D011341:Probucol