Molecular and immunological effects of ivermectin and/or low dose gamma-radiation on Schistosoma Mansoni infected mice

Abstract Background Schistosomiasis remains a public health concern with limited therapeutic options and rising resistance to praziquantel. Aim To evaluate the efficacy of ivermectin, alone and combined with low dose gamma-radiation, against Schistosoma mansoni infection. Methods Through a controlled experimental study, a total number of 40 male CD-1 mice were divided into five equal groups: an uninfected control group, an infected untreated group, and three infected treated groups (treated with ivermectin, treated with low-dose gamma-radiation, and treated with a combination of both ivermectin and low-dose gamma-radiation, respectively). Parasitological, biochemical, immunological, molecular, and histopathological parameters were analyzed. Results Compared to the normal control group, untreated infected mice showed markedly high hepatic and intestinal ova counts, and splenic lymphocytosis, along with significantly elevated liver enzymes activity (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase), and hepatic malondialdehyde, interleukin-18 levels and interferon-gamma gene expression, together with marked reductions in hepatic antioxidant markers (superoxide dismutase and reduced glutathione), interleukin-10 gene expression and phytohaemagglutinin-induced lymphocyte proliferative response, in addition to hepatic and intestinal histopathological alterations. Treatment with ivermectin and/or low dose gamma-radiation resulted in improvement of all these parameters. The combined treatment group demonstrated the most significant therapeutic impact. Conclusion Ivermectin and low dose gamma-radiation exhibit promising synergistic effects, offering a potential adjunct strategy to improve schistosomiasis outcomes and counteract drug resistance.