Efficacy of Triclabendazole: study of some detoxifying and antioxidant enzymes in human fascioliasis and/or schistosomiasis and in Fasciola gigantica worms exposed to triclabendazole metabolite.

Abstract

Human fascioliasis has recently been reported in several countries including Egypt. The disease has been identified as a cause of hepatic disorder.

In Egypt, schistosomiasis is the commonest disease with up to 36.4% of the rural populations in endemic areas affected, and is responsible for 70% of chronic liver disease among adult.

Combined infection with both schistosomiasis and fascioliasis is an increasing problem among Egyptians in rural communities causing liver damage, including periportal fibrosis.

TCBZ, in its veterinary form was considered the fasciolicide of choice in treatment of acute and chronic fascioliasis. Recently Novartis provided a newly preparea TCBZ tablets for human use (Egaten, Novartis Pharma AG, Bale, Switzerland). In Egypt, since combined infection with fascioliasis and schistosomiasis is prevalent, a drug against both parasites is highly needed.

The infection process is believed to result in increased production of free radical and hydroxyl radicals. Therefore, the body has evolved a complex defense strategy to minimize the damaging effects of these oxidants. Central to this defense are the antioxidant enzymes of the blood. They include SOD, CAT, GSH, GPx, GR, GST and G6-PD. Erythrocyte C /Zn SOD accelerates the dismutation of 02•- to H2 0z and 02. The selenium containing enzyme GPx detoxifies H2 02 by utilizing reduced glutathione and H202 as substrates to yield H2 0 and oxidized glutathione (GSSG); the GSSG, in turn, is reduced to GSH by the enzyme GR which requires NADPH as reductant; the latter is supplied via the enzyme G6PD. Catalase is a large enzyme containing haem-bound iron at its active sites. It removes H202 by breaking it down directly to 02 . GST is an ubiquitous house-keeping enzyme found in nearly all animals. Besides being responsible for general cell function, they act to detoxifY the se6ondary products of lipid peroxidation produced via immune­ initiated free radical attack.