Therapeutic effect of alpha lipoic acid combined with praziquantel on liver fibrosis induced by Schistosoma mansoni challenged mice

Abstract

Schistosomiasis is an endemic disease in 74 countries causing more than 250,000 deaths every year. Accordingly, the development of an effective drug for eradication of schistosomiasis is an open research field. The current chemotherapy for control is praziquantel (PZQ). However, PZQ does not improve liver fibrosis. Therefore, the aim of this study is to evaluate the combined effect of alpha lipoic acid (ALA) with PZQ on the liver fibrosis induced by Schistosoma mansoni challenged mice. Evaluation was based on the worm burden count, ova load, granuloma size, and histopathology of the liver. Reduced glutathione (GSH) was measured in the tissue as a biomarker for impaired antioxidant function. Malondialdehyde (MDA) was also measured in the tissue as a biomarker for oxidative stress. The serum level of matrix metalloproteinase 1 was measured as a biomarker for fibrotic status of the liver. Liver function enzymes such as ALT, AST, and GGT were also measured. Four groups of ten mice each were used in this study. The first group was infected with 50 ± 10 S. mansoni cercariae. The second group was also infected and was treated with PZQ 9 weeks post-infection (PI). The third group was treated with PZQ and ALA 9 weeks PI. The fourth group was used a healthy control. The present study revealed remarkable improvement in all parameters measured (parasitological and biochemical) as well as significant improvement of hepatic pathology in the third group which was treated with PZQ and ALA. The treatment of mice with PZQ and ALA results in reduction in the worm burden, egg count, and granuloma size. Furthermore, this combined treatment increased the tissue level of the antioxidant (GSH) and decreased the tissue level of MDA in this group.

Transdermal praziquantel administration attenuates hepatic granulomatosis in mice infected with Schistosoma japonicum

“…Previous reports indicated that the reversibility of inflammation and liver fibrosis may be possible using PZQ treatment for schistosome infection in animal models (Abdel-Hafeez et al 2012;Huang et al 2011;Liang et al 2011;Mata-Santos et al 2010). We have also found that there was a significant decrease of granuloma size, reduction of liver, and spleen enlargement after killing adult worms (Fig.…”

“…Mean values of granuloma areas in every slaughtered period were used for statistical analysis. Detailed methodology of the hepatic histopathology and granuloma measurement could refer to previous literatures (Abdel-Hafeez et al 2012;Mata-Santos et al 2010). …”

In vitro evaluation of the schistosomicidal effect of the extracts, fractions and major 3-hydroxy-2,6-dialkyl-substituted piperidine alkaloids from the flowers of Senna spectabilis (Fabaceae)

“…Due to the warnings about drug resistance, possible infection recurrence, low efficacy in some cases and very restricted therapeutic alternatives, the search for new drug prototypes is a continuous challenge and must be encouraged in academia and the pharmaceutical industry. 6,7 In the past few years, the interest in natural products as a potential source for the treatment of parasitic diseases has grown. 8 The objective of these studies is to propose alternative methods for the treatment of these diseases, especially for neglected ones, such as schistosomiasis, 9 since this has left researchers on alert regarding the development of resistance to the only drug used for its treatment.…”

Effect of Crocus sativus aqueous extract (saffron) on Schistosoma mansoni worms in experimentally infected mice

“…Treatment of S. mansoni infected mice with PZQ alone or in combination with CSE showed significant increase in SOD and catalase levels. Several studies found that PZQ diminishes oxidative stress in schistosomiasis by increasing antioxidant enzyme activities (Abdel-Hafeez et al, 2012;Rizk et al, 2012).…”