Immunohistopathological changes in murine Schistosomiasis mansoni under the influence of N-acetyl-L-cysteine

Abstract

The main pathology associated with Schistosomiasis mansoni is granulomatous inflammation that may develop into hepatosplenic disease with fibrosis and hepatoesplenomegaly. It is known that N-acetyl-L-cysteine (NAC) reduces tissue damage in chronic liver diseases owing to its anti-inflammatory, antioxidant, and detoxifying properties. In this study, we investigated the imunohistopathological changes in murine schistosomiasis mansoni under the influence of NAC, in combination with Praziquantel (PZQ) or not. Three groups of mice were formed to evaluate the effects of NAC during infection in the acute, intermediate, and chronic phases. Each group was further subdivided into four subgroups: NAC, PZQ, NAC + PZQ and control (without treatment). Oral administration of NAC (200 mg/kg/day) was carried out on the first day after infection for the acute phase and on the 45th for the intermediate and chronic phases for 59 and 45, 75 days, respectively. PZQ (100 mg/kg/day), was given orally by gavage from the 45th to 49th day after infection. Histopathological analysis of liver tissue provided evidence that combined NAC + PZQ treatment reduced the development of granulomas observed in the chronic phase. Animals treated with NAC and/or PZQ showed a reduction in the size of granulomas and all those treated with NAC exhibited a lower degree of fibrosis. In all groups, NAC decreased the synthesis of interferon-γ and nitric oxide, while increasing the levels of interleukin-10, but it did not influence the production of interleukin-4. On the whole, NAC treatment induced an immunomodulatory effect and reduced liver damage during the granulomatous inflammation in S. mansoni-infected mice.

Immunomodulation of liver injury by Ascaris suum extract in an experimental model of autoimmune hepatitis

“…Morphometric study was obtained using ImageJ software (National Institutes of Health, Bethesda, MD), by measuring the concentration of collagen from the blue stain intensity. At least 20 random photographs were taken by field (original magnification× 100) for analysis (de Lima Aires et al 2012). …”

Current and Novel Therapies Against Helminthic Infections: The Potential of Antioxidants Combined with Drugs

“…The increase of antioxidant enzymes activity is usually accompanied by reduction on granuloma size and number, resulting in improvement of the liver architecture and functions [108,125,128,129,132,133]. Another interesting aspect of antioxidants is that they could modulate and immunomodulate response and promote alteration in some cytokines [134][135][136][137][138], which could be also helpful to reduce the size and number of granulomata.…”

Drug Repurposing for Schistosomiasis: Combinations of Drugs or Biomolecules

“…In recent times, studies evaluating efficacy of antioxidants, alone or concurrently with antischistosomal drugs targeting not only parasite but also pathologies associated to infection have been reported [ 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 ] ( Table 1 and Figure 5 ).…”

“…Besides antischistosomal activity and ability to restore liver functions, antioxidants modulate and immunomodulatory response promoting alteration in some cytokines [ 122 , 126 , 133 , 136 , 139 ]. Cytokines play an important role in immunomodulation during schistosomiasis.…”

“…The dissimilarity of results obtained might be related to sampling time of experiment performed by Sheir and colleagues, which occurs after granuloma formation [ 131 ]. Moreover, treatment with N -acetylcysteine (NAC, Figure 8 ) increase synthesis of IL-10 which regulates the synthesis of several pro-inflammatory cytokines and is considered an efficient inhibitor of INF-γ, IL-12 and IL-4 [ 139 ].…”