The effect of Nigella sativa oil against the liver damage induced by Schistosoma mansoni infection in mice

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Abstract

It has been reported that Nigella sativa oil possesses anticestode and antinematode actions. Besides, it produced a hepatoprotective effect in some models of liver toxicity. Therefore, our aim in this work was to study the effect of the Nigella oil (N.O) on Schistosomiasis mansoni infected mice. The oil was given in two dose levels (2.5 and 5 ml/kg, orally for two weeks) either alone or in combination with praziquantel (PZQ), the drug of choice for the treatment of schistosomiasis. Three aspects of drug action were investigated, the effect on Schistosomiasis mansoni infection, the effect on liver functions, and on redox state. The parasitological investigation included worm distribution, oogram pattern and ova count. Furthermore, liver granuloma diameters were measured. The biochemical parameters were the serum level of l-alanine aminotransferase (ALT), γ-glutamyl transferase (GGT), alkaline phosphatase (AP), albumin (Alb) and total protein. Moreover, to assess the antioxidant capability of the Nigella oil, four parameters were studied, viz., liver lipid peroxide (LPD) and reduced glutathione (GSH) contents and the activity of the defence enzyme superoxide dismutase (SOD) and lactate dehydrogenase (LDH). When the oil was given alone, it reduced the number of S. mansoni worms in the liver and decreased the total number of ova deposited in both the liver and the intestine. Furthermore, it increased the number of dead ova in the intestinal wall and reduced the granuloma diameters markedly. When N.O was administered in combination with PZQ, the most prominent effect was a further lowering in the dead ova number over that produced by PZQ alone. Concerning the biochemical parameters, infection of mice with S. mansoni produced a pronounced elevation in the serum activity of ALT, GGT, with a slight increase in AP level. However, it tended to reduce serum albumin level. These changes were accompanied with an alteration in the liver contents of LPD and GSH along with a significant decline in the activity of the cytosolic SOD and LDH. Administration of Nigella sativa oil succeeded partially to correct the previous changes in ALT, GGT, AP activity, as well as the Alb content in serum. However, it failed in the liver to restore either LPD and GSH content or LDH and SOD activities to normal level. These results suggest that Nigella sativa oil may play a role against the alterations caused by S. mansoni infection, an effect which may be induced partly by improving the immunological host system and to some extent with its antioxidant effect.

Introduction

The seeds of Nigella sativa L. (Ranunculaceae), sometimes known as black seed, black cumin or habatul Barakah have long been used in the Middle East as a traditional medicine for a variety of complaints, headache, cough, flatulence, as a choleretic, antispasmodic and uricosuric (Boulos, 1983). In recent years, the seeds have been subjected to a range of pharmacological investigations. The data suggest that the seeds, and the major active constituent thymoquinone, exhibited hepatoprotective effect against liver damage induced by carbon tetrachloride (Al-Gharably et al., 1997, Nagi et al., 1999), and tert-butyl hydroper-oxide (Daba and Abdel Rahman, 1998). Most of the hepatoprotective drugs belong to the group of free radical scavengers, and their mechanism of action involves membrane stabilization, neutralization of free radicals and immuno-modulation. The inhibitory effects of the crude fixed oil and pure thymoquinone on membrane lipid peroxidation have been demonstrated (Houghton et al., 1995, Nagi et al., 1999). Besides, the essential oil was shown to have anthelmentic activity (Agarwal et al., 1979) and the seeds were effective against cestodes and nematodes (Akhtar and Rifaat, 1991). In view of these findings, and because in schistosomiasis, oxidative processes occurred at the site of granulomatous inflammation (Gharib et al., 1999), this study was undertaken to determine the possible antischistosomal effect of the expressed oil of N. sativa in S. mansoni infected mice, and to relate this to its hepatoprotective and antioxidant actions.

Section snippets

Animals

Male Swiss albino mice, weighing 18–20 g bred at the Experimental Research centre of Theodor Bilharz Institute, Cairo, Egypt, were used for the study. They were housed in seven groups with free access to standard lab chow (El Nasr Lab Chem. Co, Egypt) and tap water.

Infection of animals

Six groups were infected by tail immersion technique according to the method of Olivier and Stirewalt (1952) with 80±10 cercariae per mouse of an Egyptian strain of S. mansoni.

Animal groups

After 7 weeks, infected animals were divided into 6

Results

In the infected control group total number of worms counted 27±2.8, was divided between liver (43%) and portomesenteric vein (57%). Treatment of mice with N.O alone reduced the total number of worm burden at the two dose levels (22, 32%) respectively, especially those in the liver (Table 1). On the other hand, PZQ caused a marked reduction in worm burden reaching 98, with 60% of the worms shifted to the liver. This inhibition was slightly improved when PZQ was given in combination with 5 ml/kg

Discussion

Schistosomiasis is one of the most widespread parasitic infections. Hepatic fibrosis, resulting from S. mansoni infection, is of primary importance among chronic liver diseases worldwide. Early work by Warren (1973) has demonstrated that schistosome eggs or soluble egg antigens (SEA) are primarily responsible for host reactions associated with the infection. The eggs, swept into the liver, elicit T-cell dependent responses leading to macrophage activation and granuloma formation around them (

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