ABSTRACT
The genotoxic potential of podophyllin (PD) was investigated in this study. PD increased bacterial revertants and abnormal chromosomal structures in a concentration-dependent manner, both with and without metabolic activating enzymes, and increased the incidence of micronuclei in imprinted control region mouse reticulocytes. Results from three studied constituents of PD, such as podophyllotoxin, kampferol, and quercetin, suggested that the mutagenic effect of PD was not due to the presence of podophyllotoxin, kampferol, and quercetin and might be related to other components and the formation of reactive oxygen species. The detailed mutagenic mechanisms need further investigation, and the medicinal use of PD needs to be cautioned against.
Subject(s)
Kaempferols/toxicity , Podophyllin/toxicity , Quercetin/toxicity , Reactive Oxygen Species/metabolism , Animals , Chromosome Aberrations/drug effects , Dose-Response Relationship, Drug , Kaempferols/isolation & purification , Male , Mice , Mice, Inbred ICR , Micronuclei, Chromosome-Defective/drug effects , Mutagenicity Tests , Mutagens/chemistry , Mutagens/toxicity , Podophyllin/administration & dosage , Podophyllin/chemistry , Podophyllotoxin/isolation & purification , Podophyllotoxin/toxicity , Quercetin/isolation & purification , Rats , Rats, Wistar , Reticulocytes/drug effects , Reticulocytes/metabolismABSTRACT
Topical application of podophyllin solution, long considered the therapy of first choice against condylomata acuminata, can no longer be recommended due to its low efficacy and gross toxicity. Self-treatment with 0.15-0.5% purified podophyllotoxin preparations, applied twice daily for 3 days, is now advocated as the alternative first-line therapy of choice, when significant improvement is conveniently, and cost-effectively, accomplished within a few weeks. This review provides a summary of the comparative efficacy and utility of podophyllin versus podophyllotoxin as well as a compilation of in vivo and in vitro safety evaluations. In light of overwhelming safety and efficacy data in favor of podophyllotoxin-derived products, it is concluded that podophyllin preparations have no place in the modern treatment portfolio for anogenital warts.
Subject(s)
Condylomata Acuminata/drug therapy , Keratolytic Agents/toxicity , Podophyllin/toxicity , Podophyllotoxin/toxicity , Administration, Topical , Animals , Cats , Clinical Trials as Topic , Condylomata Acuminata/epidemiology , Evidence-Based Medicine , Guinea Pigs , Humans , Keratolytic Agents/administration & dosage , Mice , Mutagenicity Tests , Podophyllin/administration & dosage , Podophyllotoxin/administration & dosage , Practice Guidelines as Topic , Rabbits , Rats , Reproduction/drug effects , Toxicity TestsABSTRACT
Podophyllin, a plant derivative of variable composition, is used widely within New Zealand as a treatment for genital warts. One local source of podophyllin has been tested for ability to cause mutagenic effects in Salmonella typhimurium as well as for effects on chromosomes of Chinese hamster AA8 cells. Although only weakly mutagenic in one strain of Salmonella, podophyllin caused structural aberrations as well as changes in chromosome number in the Chinese hamster cells. The range of aberrations was similar to those caused by teniposide, a close structural relative of the major component, which was used as a positive control in the Chinese hamster cell experiments. A literature review revealed that podophyllin was shown to cause changes of chromosome number in the mouse cervix in vivo, although aberrations were not studied. Patients treated with podophyllin will usually possess one form of the papilloma virus, and this itself may have some oncogenic potential. We suggest that podophyllin could potentiate these effects and question its continued widespread use.
Subject(s)
Chromosome Aberrations , Condylomata Acuminata/drug therapy , Podophyllin/toxicity , Animals , Cells, Cultured , Cricetinae , Cricetulus , Mutagenicity TestsABSTRACT
A case demonstrating suspected teratogenic effects of topical podophylium is presented. Podophyllum resin was applied five times for a duration of 4 hr from the 23rd to the 29th week of pregnancy. At birth a simian crease on the left hand and a preauricular skin tag were noted. It is suggested that podophyllum be avoided during pregnancy. Alternative treatment for warts of the vaginal, perineal, or anal area are presented.
Subject(s)
Podophyllin/toxicity , Teratogens , Abnormalities, Drug-Induced/etiology , Administration, Topical , Adult , Chloroquine/toxicity , Condylomata Acuminata/drug therapy , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/drug therapyABSTRACT
A case is reported of apparent podophyllum toxicity. The patient was a 17-year-old female Indian who had received some 3 to 8 cc of a 20 percent mixture of podophyllum resin in compound tincture of benzoin (approximately equal to 0.4 gm of podophylotoxin) as an application to her vulvar condylomata. She returned to the hospital 20 hours after application in a comatose state. On examination she demonstrated severe toxicity including bone marrow, liver, and central nervous system. She required a charcoal hemoperfusion at the University of Colorado, and six months after the event has several neurologic and physiologic sequelae. Podophyllum is a potentially severely toxic drug. Great care must be taken when treating patients with this drug. A large mass of condylomata or the status of pregnancy should be relative contraindications to the use of podophyllum.
