The efficacy of cercarial antigen loaded on nanoparticles as a potential vaccine candidate in Schistosoma mansoni-infected mice.

Schistosomiasis is one of the most common causes of morbidity and mortality from parasitic diseases. Mass treatment has proven to be insufficient because of repeated infection after treatment and the appearance of strains resistant to drug therapy. Hence, immunization is a new approach to control the disease and limit the pathological consequences of schistosomiasis. To evaluate the prophylactic effect of Cercarial antigen (CAP) loaded on chitosan nanoparticles (CSNPs) as a potential vaccine against Schistosoma mansoni-infected mice. 130 mice divided into 2 groups were used: Group I: Control groups (50 mice) subdivided into subgroup Ia (10 mice): Non-infected mice (normal control), subgroup Ib (20 mice): Schistosoma infected mice (infected control) and subgroup Ic (20 mice): Non-infected mice receiving NPs only. Group II: Vaccinated group (80 mice) subdivided equally into subgroup IIa (CAP): Received cercarial antigen and subgroup IIb (CAP + CSNP): Received cercarial antigen loaded on chitosan NPs then both vaccinated groups were infected with S. mansoni 3 weeks following the initial vaccination dose. CAP + CSNP and CAP groups showed significant reduction in adult worms count, hepatic egg count, hepatic granulomas number and size in comparison to the infected control group. Elevation of serum IgG and IgM levels, CD4+ and CD8+ T cell frequencies, IL-4, IL-10 and INF-γ levels was more significant in CAP + CSNP group than CAP group. CAP + CSNP is a promising new preparation of Schistosomal antigens that gave better results than immunization with CAP alone. CSNPs enhanced the immune and protective effect of CAP as validated by parasitological, histopathological and immunohistochemical studies.

Anthelmintic potential of sulphonamides and Cucurbita pepo seeds extract on Heterophyes heterophyes experimentally infected mice.

Since 1980s, no new drugs were described for treatment of heterophyiasis with many side effects of the currently used drug; praziquantel. This work aimed to study the therapeutic effect of clorsulon (sulphoamide) and aqueous extract of Cucurbita pepo in the treatment of experimental heterophyiasis. Mice were infected with encysted metacercaiae of Heterophyes heterophyes obtained from infected fish flesh. Mice were divided into five groups according to the drug used. The treatment started two weeks post-infection. Our results showed reduction of the recovered worm count with high efficacy of clorsulon and a moderate effect of C. pepo which was increased in the second week with much improvement of the intestinal histopathological changes. Scanning electron microscopy of adult H. heterophyes obtained from the intestine of mice treated with praziquantel appeared contracted with multiple small vesicles over the dorsal surface. Clorsulon produced loss of the spines on the lateral sides of the parasite with few vesicles whereas C. pepo seeds showed complete loss of the spines. In conclusion, clorsulon has high efficacy against H. heterophyes infection. Although the extract of C. pepo showed moderate curative effect against this parasite, it can be used in combination with other agents for a better synergistic effect.

Stem cell-derived exosomes as a potential therapy for schistosomal hepatic fibrosis in experimental animals.

Schistosomiasis is a neglected tropical disease. Egg-induced granuloma formation and tissue fibrosis are the main causes of the high morbidity and mortality of schistosomiasis. Mesenchymal stem cells (MSCs)-derived exosomes play an important role with a superior safety profile than MSCs in the treatment of liver fibrosis. Therefore, the aim of this study was to investigate the potential therapeutic effect of MSCs-derived exosomes on schistosomal hepatic fibrosis. Exosomes were isolated from bone marrow MSCs and characterized. A total of 85 mice were divided into four groups: group I (control group), group II (PZQ group) infected and treated with PZQ, group III (EXO group) infected and treated with MSCs-derived exosomes and group IV (PZQ+EXO group) infected and treated with both PZQ and MSCs-derived exosomes. Assessment of treatment efficacy was evaluated by histopathological and immunohistochemical examination of liver sections by proliferating cell nuclear antigen (PCNA) and nuclear factor-κB (NF-κB). The results showed significant reduction of the number and diameter of hepatic granulomas, hepatic fibrosis, upregulation of PCNA expression and reduction of NF-κB expression in EXO and PZQ+EXO groups as compared to other groups at all durations post infection. Additionally, more improvement was observed in PZQ+EXO group. In conclusion, MSCs-derived exosomes are a promising agent for the treatment of schistosomal hepatic fibrosis, and their combination with PZQ shows a synergistic action including antifibrotic and anti-inflammatory effects. However, further studies are required to establish their functional components and their mechanisms of action.

Surfactant vesicles for enhanced antitoxoplasmic effect of norfloxacin: In vitro and in vivo evaluations.

The goal was to scrutinize niosomes as potential carriers for enhanced efficacy of norfloxacin against Toxoplasma gondii RH strain. This was assessed in vitro and in vivo. Standard niosomes of Span 60 and cholesterol were prepared. Gelucire 48/16 or Tween 80 was incorporated as hydrophilic fluidizer. The prepared vesicles were characterized for shape, size, viscosity and norfloxacin release. The in vitro anti-Toxoplasma was assessed by monitoring tachyzoites viability after incubation with niosomes. In vivo efficacy of niosomes encapsulated norfloxacin was evaluated on infected mice. Transmission electron micrographs showed nano-sized spherical vesicles. Norfloxacin release varied with niosomal composition to show faster liberation in presence of fluidizing agent. The half maximum effective concentration of norfloxacin against tachyzoites (EC50) was significantly reduced after niosomal encapsulation compared with simple drug solution with no significant difference between vesicular formulations. Tachyzoite count in the peritoneal fluid of infected mice was reduced by 45.2, 90.8, 88.3 and 84% after treatment with simple drug dispersion, standard niosomes, Gelucire containing and Tween containing vesicles, respectively compared to infected untreated mice. These results correlate with the in vitro data and reflects the efficacy of niosomes. The study introduced surfactant vesicles as a tool for enhanced efficacy of norfloxacin against toxoplasma.

Immunomodulatory effects of chronic trichinellosis on Toxoplasma gondii RH virulent strain in experimental rats.

Mixed parasitic infections could affect the host immunological responses and re-design the pathogenesis of each other. The impact of Toxoplasma gondii (T. gondii) and Trichinella spiralis (T. spiralis) co-infection on the immune response remains unclear. The objective of the present study was to investigate the possible effect of chronic trichinellosis on the immune response of rats infected with T. gondii virulent RH strain. Animals were divided into four groups: group I: non-infected negative control; group II: infected with T. spiralis; group III: infected with T. gondii and group IV: infected with T. spiralis then infected with T. gondii 35 days post T. spiralis infection (co-infected group). The interaction between T. spiralis and T. gondii was evaluated by histopathological examination of liver and brain tissues, immunohistochemical expression of inducible nitric oxide synthase (iNOS), and ß-catenin in the brain tissues, and CD4+ and CD8+ T cells percentages, and tumor necrosis factor (TNF)-alpha expression in the spleen tissues. Along with, splenic interleukin (IL)-4 and IL-10 mRNA expression levels were measured 15 days post-Toxoplasma infection. Our study revealed that prior infection with T. spiralis leads to attenuation of Th1 response against T. gondii, including iNOS, TNF-α, and CD8+ T-cell response with improvement of the histopathological changes in the tissues. In conclusion, in the co-infected rats, a balanced immune response has been developed with the end result, improvement of the histopathological changes in the liver and brain.

Human umbilical cord blood mesenchymal stem cells as a potential therapy for schistosomal hepatic fibrosis: an experimental study.

The objective of our study was to assess the effect of human umbilical cord blood (HUCB) mesenchymal stem cells (MSCs) transplantation on schistosomal hepatic fibrosis in mice. The study animals were divided into three groups. Group I is a control group, where the mice were infected with Schistosoma mansoni cercariae and remained untreated. The mice of the other two groups were infected and treated with either praziquantel (Group II) or HUCB-MSCs (Group III). Liver function tests, as well as histopathological evaluation of liver fibrosis using hematoxylin and eosin and Masson's trichrome stains, were performed. Additionally, an immunohistochemical study was carried out using anti-glial fibrillary acidic protein (GFAP) in hepatic stellate cells. Compared to the control group, the treated (praziquantel and MSCs) groups showed a substantial improvement, with a significant difference regarding the histopathological evaluation of liver fibrosis in the MSCs-treated group. In conclusion, MSCs could be a promising and efficient cell therapy for liver fibrosis.

Trichinella spiralis-derived extracellular vesicles induce a protective immunity against larval challenge in mice.

Human trichinellosis is a serious disease with no effective treatment till now. Recently, the protective immunity induced by parasite-derived extracellular vesicles (EVs) are studied for some parasites such as Echinostoma caproni. The current study aimed to investigate the novel Trichinella spiralis-derived EVs as a potential vaccine candidate for the first time in a mouse model. Trichinella spiralis EVs were isolated and identified using transmission electron microscopy, gel electrophoresis, protein content measurements, and beads-based flow cytometry. Vaccination was done by subcutaneous injection of two doses of 3.5 µg T. spiralis-derived EVs. We observed a significant reduction in T. spiralis adult worm and muscle larval counts in mice immunized with T. spiralis-derived EVs (EVs-Ts group) and controlled inflammatory changes in the intestine and muscles. The EVs-Ts group showed a higher level of IFN- γ, whereas the IL-4 secretion was elevated more in the EVs group (EVs group) and showed a lower level after challenge with T. spiralis infection (EVs-Ts group). This implies a mixed Th1/Th2 immune response with obvious Th1 polarization. Moreover, elevation of serum T. spiralis-specific IgG was reported. In conclusion, this preliminary study provides T. spiralis EVs as a promising candidate for future development of anti-Trichinella vaccine.

Different panel of toll-like receptors expression during chronic Schistosoma mansoni infection in experimental animals.

BACKGROUND: Many studies have reported the immunomodulatory effect of helminths to avoid the lethal immunopathology. During schistosomiasis, the immune response is orchestrated by toll-like receptors (TLRs). Modulating TLRs can alter the function of antigen presentation cells with the shift of the host's Th1 response to a dominant regulatory Th2 response. The objective of our study was to clarify which TLRs are related to the immune response of chronic Schistosoma infection. METHODS: The study animals were divided into two groups; group I: uninfected mice; control group and group II: Schistosoma mansoni infected mice. mRNA expression of TLR2, 3, 4, 7, and 9 in different organs (liver, large intestine, and spleen) were assessed on day 90 post-infection. RESULTS: TLR gene expression has changed depending on the tissue studied as the mRNA level of TLR2, TLR7, and TLR9 were significantly upregulated in all examined organs while TLR3 expression showed only significant upregulation in the liver of infected mice. On the other hand, TLR4 expression was significantly upregulated in the liver while significantly downregulated in the large intestine. CONCLUSION: This study provides a better understanding of TLRs profile in different organs against S. mansoni parasites during the chronic phase of infection.

The Apoptotic Effect of Trichinella spiralis Infection Against Experimentally Induced Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common type of cancer. Prognosis of HCC remains unsatisfactory. Therefore, developing new therapeutic modalities is still mandatory. Tumor biotherapy is a novel concept developed as a therapeutic strategy for cancer treatment. There is a similarity between the regulatory mechanism of Trichinella spiralis nurse cell formation and tumor cell apoptosis signal regulation. OBJECTIVES: Induction of apoptosis by T. spiralis can represent a new strategy for tumor treatment. METHODS: Experimental animals were divided in four groups; negative control (GI), T. spiralis infected (GII), induced HCC (GIII) and HCC then infected with T. spiralis (GIV). The apoptotic effect of T. spiralis infection was assessed by histopathological and immunohistochemical staining of B-cell lymphoma 2 (Bcl-2). RESULTS: We found higher survival rate of rats and decreased weight of their livers with no nodules in HCC- T. spiralis group as compared to HCC group. Improvement of the dysplastic changes and increased apoptotic bodies which was confirmed by decreased expression of Bcl-2 reported in HCC- T. spiralis group. CONCLUSION: Trichinella-induced apoptosis can be a contributing mechanism of the anti-tumor effect of T. spiralis infection. Our results showed a certain level of decreased progression of the tumor in HCC-T. spiralis group as indicated by increased rate of apoptosis and subsequently had a positive impact on the survival of rats.
.

Age-related changes in cerebral congenital toxoplasmosis: Histopathological and immunohistochemical evaluation.

Congenital toxoplasmosis is a widespread worldwide disease producing varying degrees of damage to the fetus including ocular and neurological impairment. However, the underlying mechanisms are not yet clear. Therefore, the current study aimed to investigate the progress of congenital cerebral toxoplasmosis in experimentally infected offspring animal model at different age groups till become adults. To fulfill this aim, the offspring of Me49 T. gondii infected pregnant mice were divided into groups; embryo, infant, young and adult phases. Blood and brain samples were collected for further hormonal and histopathological studies and immunohistochemical staining of glial fibrillary acidic protein (GFAP) and synaptophysin (SYN). Our results showed several encephalitic changes in the infected groups ranging from gliosis to reduced cortical cell number and fibrinoid degeneration of the brain. We showed increased expression of GFAP and SYN indicating activation of astrocytes and modification of the synaptic function, respectively. These changes started intrauterine following congenital infection and increased progressively afterward. Moreover, infected mice had elevated corticosterone levels. In conclusion, the current study provided new evidences for the cellular changes especially in the infected embryo and highlighted the role of GFAP and SYN that may be used as indicators for T. gondii-related neuropathy.

Parasite-bacteria interrelationship.

Parasites and bacteria have co-evolved with humankind, and they interact all the time in a myriad of ways. For example, some bacterial infections result from parasite-dwelling bacteria as in the case of Salmonella infection during schistosomiasis. Other bacteria synergize with parasites in the evolution of human disease as in the case of the interplay between Wolbachia endosymbiont bacteria and filarial nematodes as well as the interaction between Gram-negative bacteria and Schistosoma haematobium in the pathogenesis of urinary bladder cancer. Moreover, secondary bacterial infections may complicate several parasitic diseases such as visceral leishmaniasis and malaria, due to immunosuppression of the host during parasitic infections. Also, bacteria may colonize the parasitic lesions; for example, hydatid cysts and skin lesions of ectoparasites. Remarkably, some parasitic helminths and arthropods exhibit antibacterial activity usually by the release of specific antimicrobial products. Lastly, some parasite-bacteria interactions are induced as when using probiotic bacteria to modulate the outcome of a variety of parasitic infections. In sum, parasite-bacteria interactions involve intricate processes that never cease to intrigue the researchers. However, understanding and exploiting these interactions could have prophylactic and curative potential for infections by both types of pathogens.

Chitosan coated nanostructured lipid carriers for enhanced in vivo efficacy of albendazole against Trichinella spiralis.

The study investigated chitosan coated nanostructured lipid carriers (NLCs) for oral delivery of albendazole in treatment of trichinellosis. NLCs comprised precirol and oleic acid with Tween and Span 80. Dicetylphosphate was used as charging agent to allow chitosan coating. Trichinella spiralis infected mice were used and albendazole suspension, coated or uncoated NLCs were orally administered at different stages of infection. NLCs were spherical with size of 188 and 200 nm for coated and uncoated NLC, respectively. Treatment during intestinal phase reduced worm count with NLCs showing better rank. This was reflected further by reduced larvae count and improved histopathological features. Starting treatment in the migrating phase reduced larval count by 62.9, 99.6 and 89.5 % after administration of suspension, coated and uncoated NLCs, respectively. The same rank was recorded for the encysted phase. NLCs enhanced the efficacy of albendazole against Trichinella spiralis compared with suspension with chitosan coated NLCs being superior.

Ivermectin: From theory to clinical application.

Approximately 250 million people have been using ivermectin (IVM) annually to combat many parasitic diseases including filariasis, onchocerciasis, strongyloidiasis, scabies and pediculosis. Many clinical studies have proven its efficacy against these diseases and have reported the optimum dose and duration of treatment. Moreover, its antiparasitic range has increased to cover more parasitic infections, but it still requires further exploration, e.g. for trichinosis and myiasis. Furthermore, IVM showed high efficacy in killing vectors of disease-causing parasites such as mosquitoes, sandflies and tsetse flies. The World Health Organization (WHO) has managed many control programmes involving the use of IVM to achieve elimination of onchocerciasis and lymphatic filariasis and to reduce malaria transmission. However, IVM is not exempt from the possibility of resistance and, certainly, its intensive use has led to the emergence of resistance in some parasites. Recent research is investigating the possibility of novel drug delivery systems for IVM that increase its potential to treat a new range of diseases and to overcome the possibility of drug resistance. This review highlights the most common human uses of IVM, with special reference to the new and promising properties of IVM.

Can the route of Toxoplasma gondii infection affect the ophthalmic outcomes?

Ocular toxoplasmosis is the most common cause of retinochoroiditis worldwide in humans. Some studies highlighted the idea that ocular lesions differ according to the route of infection but none of them mimicked the natural route. The current study aimed to investigate the ophthalmic outcomes in congenital and oral routes of infection with Toxoplasma in experimental animals. Mice were divided into three groups; group I: congenital infection, group II: acquired oral infection and group III: non-infected. We used Me49 chronic low-virulence T. gondii strain. We found that retina is the most affected part in both modes of infections. However, the retinal changes are different and more pronounced in case of congenital infection. The congenitally infected mice showed retinal lesions e.g. total detachment of retinal pigment epithelium from the photoreceptor layer and irregular arrangement of retinal layers. More severe damage was observed in mice infected early in pregnancy. While the postnatal orally infected mice showed fewer changes. In conclusion, the routes of Toxoplasma infection affect the ophthalmic outcomes and this may be the case in human disease. Although both are vision threatening, it seems that the prognosis of postnatal acquired ocular toxoplasmosis is better than that of congenital disease.

Hybrid feature extraction techniques for microscopic hepatic fibrosis classification.

Chronic liver diseases' hallmark is the fibrosis that results in liver function failure in advanced stages. One of the serious parasitic diseases affecting the liver tissues is schistosomiasis. Immunologic reactions to Schistosoma eggs leads to accumulation of collagen in the hepatic parenchyma causing fibrosis. Thus, monitoring and reporting the staging of the histopathological information related to liver fibrosis are essential for accurate diagnosis and therapy of the chronic liver diseases. Automated assessment of the microscopic liver tissue images is an essential process. For accurate and timeless assessment, an automated image analysis and classification of different stages of fibrosis can be employed as an efficient procedure. In this work, granuloma stages, namely cellular, fibrocellular, and fibrotic granulomas along with normal liver samples were classified after features extraction. In this work, a new hybrid combination of statistical features with empirical mode decomposition (EMD) is proposed. These combined features are further classified using the back-propagation neural network (BPNN). A comparative study of the used classifier with the support vector machine is also conducted. The comparative results established that the BPNN achieved superior accuracy of 98.3% compared to the linear SVM, quadratic SVM, and cubic SVM that provided 85%, 84%, and 80%; respectively. In conclusion, this work is of special value that provides promising results for early prediction of the liver fibrosis in schistosomiais and other fibrotic liver diseases in no time with expected better prognosis after treatment.

IMPACT OF IMMUNE SUPPRESSION ON HISTOPATHOLOGICAL AND IMMUNOLOGICAL PARAMETERS OF MICE EXPERIMENTALLY INFECTED WITH GIARDIA LAMBLIA.

Giardiasis is one of the most frequent entero-parasites worldwide; its prevalence is more common in developing countries. Giardia lamblia is considered one of the opportunistic parasites and aits clinical manifestations represent the expression of host resistance and parasite viri lence. As of chronic giardiasis cases were expected to worsen in immunosuppressed patients with development of various complications. This work assessed the histolopathological and the possible immunological effects of infection with G. lamblia in an immunosuppressed experimental animal model in comparison to immunocompetent one. Mice were divided into 4 groups;. group I: simmunocompetent (IC) mice infected with G. lamblia cysts, group II: immunosup pressed (S) mice infected with cysts, group III: uninfected immunocompetent mice and group. IV: uninfected immunosuppressed mice. From each group, small intestine was. removed for histopathological and molecular studies. Also, cyst counting in the stool of infected mice was estimated. We found that the number of G. lamblia cysts in the stool of IS mice was significantly higher than that from IC ones. Shortening of the villi was more pronounced in the IS than in IC group. Furthermore, intraepithelial lymphocytic count, goblet cell count and mast cell count were significantly decreased in the IS infected group as compared to IC ones. Expression of interleukin.6 mRNA showed high expression in IC infected mice while it was weak in IS mice. In conclusicn, the present study revealed the importance of the innate immunity presented by goblet cells, mast cells and other adaptive immunity responses; in the clearance of Giardia.

Implication of artemisinin nematocidal activity on experimental trichinellosis: In vitro and in vivo studies.

Benzimidazole drugs are used for treatment of trichinellosis, but they have a limited effect against encapsulated larval stages of Trichinella spiralis. Hence, there is a considerable interest in developing new anthelmintic drugs. Our aim is to investigate the possible effect of artemisinin on T. spiralis in in vitro and in vivo studies. T. spiralis worms were isolated from infected mice and transferred to 3 culture media; group I: with no drugs, group II: contained artemisinin and group III: contained mebendazole, then they were subjected to electron microscopic study. An in vivo study was done where mice were divided into three groups; group I: infected and untreated, group II: received artemisinin and group III: received mebendazole. The efficacy of treatment was assessed by adult and total larval counts, histopathological study of the small intestinal and muscle tissues and immunohistochemical staining of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in muscles. Adult worm teguments showed significant degeneration and destruction with both drugs. Also, significant reduction of total adult and larval counts occurred in treated groups in comparison to the control group. Histopathological examination of the small intestine and muscles showed marked improvement with reduction in the inflammatory infiltrates with both drugs. COX-2 and VEGF expressions were reduced in both treated groups with more reduction in the artemisinin-treated group. This study revealed that artemisinin has the potential to be an alternative drug against trichinellosis.

Nitazoxanide anthelmintic activity against the enteral and parenteral phases of trichinellosis in experimentally infected rats.

Most of the drugs used for the treatment of trichinellosis show a limited bioavailability and a high degree of resistance. Therefore, this study aimed to characterize the anthelmintic potential activity of nitazoxanide (NTZ) in a rat model of experimental trichinellosis. Animals were divided into three groups; group I, infected and non-treated; group II, received NTZ for three days post-infection (dpi) and group III, received NTZ 30 dpi for 14 consecutive days. Treatment efficacy was assessed by Trichinella spiralis adult and larval counts, histopathological studies of the small intestine and muscles and inducible nitric oxide synthase (iNOS) expression in the small intestine. T. spiralis adult count was reduced in NTZ -treated group (66.6%) and the larval count decreased to 68.7 and 76.7% in the early and late treatment, respectively. The infected non-treated rats showed massive inflammatory cellular infiltration in the small intestines and muscles. This inflammatory response was minor in the treated groups and was accompanied by a decrease in iNOS expression. Moreover, in group III, the larvae were replaced by homogenized substance with some destructive changes in the capsule. In conclusion, NTZ showed a promising activity against enteral and more effect in parenteral phases of trichinellosis.

Carbonic anhydrase enzyme as a potential therapeutic target for experimental trichinellosis.

Trichinellosis is a globally distributed helminthic infection. There is a considerable interest in developing new anti-helminthic drugs affecting all the developmental stages of Trichinella. Acetazolamide (carbonic anhydrase (CA) inhibitor) involves a novel mechanism of action by inhibiting such an essential enzyme for parasite metabolism. This work aimed to study the effect of acetazolamide against different stages of T. spiralis in experimental animals. Mice were divided into three groups: group I: infected and treated with acetazolamide on day 2 post infection (P.I.), group II: infected and treated with acetazolamide on day 12 P.I., and group III: infected non-treated. From each group, small intestine and muscles were removed for histopathological and immunohistochemical studies. Also, total adult and muscle larval count were estimated. We found that acetazolamide was effective in reduction of both adult and muscle larval counts. When given early, the effect was more pronounced on the adults (62.7 %). However, the efficacy of the drug against muscle larvae was increased when given late (63 %). Improvement of the intestinal histopathological changes was observed in all the treated groups. Degeneration of encysted larvae with minimal pathologic changes of infected skeletal muscle was observed in the treated groups. Expression of matrix metalloproteinase-9 showed a statistically significant decrease in the intestinal and muscle tissues in all treated groups as compared to the control group. In conclusion, the present study revealed that acetazolamide, carbonic anhydrase inhibitor, could be a promising drug against both adults and larvae of T. spiralis.

Atorvastatin and metformin administration modulates experimental Trichinella spiralis infection.

The host-parasite interaction can be altered by the changes in the host environment that may be or may not be in favor of successful invasion by the nematode parasite Trichinella spiralis. Metformin and atorvastatin are applied on a wide scale, to the degree that they could be considered as part of the host biochemical environment that can affect the parasite. Therefore, this study aimed to investigate the impact of alteration of the host's biochemical environment by these commonly used drugs upon the course of T. spiralis infection. Mice were divided into three groups: (1) received atorvastatin, (2) received metformin, and (3) untreated, then after one week, animals were infected with T. spiralis. The treatment continued until the end of the experiment. From each group, small intestines and muscles were removed for histopathological, immunohistochemical, and biochemical analyses as well as total muscle larval counts. We found that the oxidative stress and the expression of vascular endothelial growth factor (VEGF) in the muscles were significantly reduced in both drug-receiving groups, while the total larval counts in muscles were only significantly reduced in atorvastatin-receiving group as compared to the infected control group. Moreover, marked reduction in the inflammatory cellular infiltration, cyclooxygenase-2 (COX-2) expression, and oxidative stress was noted in the small intestines of the treated groups as compared to the infected control group. In conclusion, this study provides many insights into the different biochemical changes in the host that the parasite has to face. Moreover, the anti-inflammatory and anti-angiogenic effects should be taken into consideration when treating infections in patients on therapy with atorvastatin or metformin.