Modulation of the antioxidant defence in different developmental stages of Schistosoma mansoni by praziquantel and artemether.
Human schistosomiasis is a chronic and debilitating parasitic disease caused by parasitic trematode worms (schistosomes). Praziquantel (PZQ) is the drug of choice as it is active against all Schistosoma species, can be administered easily, has high cure and egg reduction rates, with no or only mild side effects. Rapid re-infection following treatment and the concerns about PZQ resistance has led to the search for new drugs to treat schistosomiasis. Significant progress has been made with artemisinin derivatives (e.g., artemether [ART]) that are used for chemoprophylaxis. This present study aims to look at the effects of ART and PZQ on the antioxidant defence of immature (three-week-old) and mature (six-week-old) stages of S. mansoni. The possible development of time- or concentration-dependent changes in oxidative stress is assessed by incubation with different sublethal drug concentrations (50, 75, 100 ng/mL for both ART and PZQ) and different time periods (one and three hours). The results indicated a time- and concentration-dependent depletion of glutathione (GSH), which was greater in the immature worms after incubation with ART. On addition of ART to the incubation medium of mature and immature worms, elevation in lipid peroxidation (TBARS) level was observed, which was time- and concentration-dependent, and more prominent in the immature schistosomes. Addition of PZQ to the incubation medium containing the immature schistosomes did not have a significant effect on TBARS level, except after three hours' incubation with the highest concentration used; however, a significant rise was seen in the mature worms. The PZQ had no effect on the activities of superoxide dismutase (SOD), glutathione peroxidase (tGPx, sGPx and nGPx) and glutathione transferase (GST) in mature or immature worms. While ART induced SOD activity in mature worms, it induced tGPx, nGPx and GST activities in a time- and concentration-dependent manner in both mature and immature worms. Activation was more prominent in the immature schistosomes. The results of the present study indicate that the immature schistosomes are more prone to oxidative killing, which probably participates in the mechanism of antischistosomal action of ART against the immature stage of S. mansoni. The results suggest that the mechanism of schistosomicidal action of PZQ is probably not substantially dependent on oxidative stress or oxidative killing.
El-Bassiouni
E A
EA
Medical Research Institute, Alexandria University, Egypt.
Helmy
M H
MH
Saad
E I
EI
El-Nabi Kamel
M A
MA
Abdel-Meguid
E
E
Hussein
H S E
HS
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D000077549:Artemether; D037621:Artemisinins / Q000494:pharmacology*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D011223:Praziquantel / Q000494:pharmacology*; D012550:Schistosoma mansoni / Q000187:drug effects*; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000378:metabolism; D012556:Schistosomicides / Q000494:pharmacology*
D000975:Antioxidants; D037621:Artemisinins; D012556:Schistosomicides; D011223:Praziquantel; D000077549:Artemether