Praziquantel (antischistosomal drug): is it clastogenic, co-clastogenic or anticlastogenic?
Schistosoma haematobium infection is the most common health problem in Egypt. It is strongly associated with the development of urinary bladder carcinoma. The actual cause for the development of cancer is still under investigations, it can be due to mechanical irritation from schistosomiasis ova, the infection itself or the drugs which are used to treat the patients. Praziquantel (PQ) is a commonly used drug to treat schistosomiasis patients. In mice, an in vivo cytogenetic study showed that PQ is not clastogenic in mice. The frequency of micronuclei in all the study groups were insignificantly different from the control group (p > 0.05). However, it enhanced the clastogenicity of benzene at a very high dose. Results from combined exposure with benzene and PQ showed a significant PQ dose-dependent increase in micronucleus frequency (p < 0.05). A metabolite study revealed that PQ enhanced the metabolism of benzene to form muconaldehyde which may be responsible for the enhancement effect. In schistosomiasis patients, two cytogenetic studies were carried out before and after treatment with PQ. In one of these studies, peripheral blood lymphocytes were examined from schistosomiasis patients to detect chromosomal aberrations (CAs) and micronuclei (MN) before and after treatment with PQ. There was no significant increase in CAs in patients compared with the controls (p > 0.05). The frequency of MN was significantly higher in the infected persons (0.59 +/- 0.44) than the control individuals (0.23 +/- 0.23) (p < 0.05). After treatment, there was no significant change in both parameters. The other study was conducted to determine whether infection with this parasite resulted in an increase of chromosomal breakage, micronuclei, in exfoliated urothelial cells. Micronucleus frequencies were significantly higher in the infected group (mean frequency, 0.84 +/- 0.69%) than among controls (mean frequency, 0.12 +/- 0.21%, p < 0.001). Micronucleus frequencies were higher in infected individuals who smoked compared with those who were non-smokers, although this effect was not significant (p > 0.05). The mean micronucleus frequencies were reduced significantly in the group of patients who were followed up (before treatment, 0.80 +/- 0.70%, after treatment, 0.19 +/- 0.23%, p < 0.001), thus supporting a direct involvement of the infection in increased chromosomal breakage in the urothelium and provide proof of the role of PQ in decreasing the risk of cancer development. At this stage, we still need to study the cytogenetic effect of human exposure to environmental agents such as pesticides, smoking, etc., together with treatment with PQ.
Anwar
W A
WA
Department of Community, Environmental and Occupational Medicine, Faculty of Medicine, Ains Shams University, Cairo, Egypt.
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001554:Benzene / Q000633:toxicity; D002869:Chromosome Aberrations; D004534:Egypt / Q000453:epidemiology; D004781:Environmental Exposure; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D006801:Humans; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D010063:Ovum / Q000502:physiology; D011223:Praziquantel / Q000494:pharmacology* / Q000627:therapeutic use* / Q000633:toxicity; D015995:Prevalence; D012553:Schistosomiasis haematobia / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D012907:Smoking; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology
D016587:Antimutagenic Agents; D009153:Mutagens; D011223:Praziquantel; D001554:Benzene