Immunomodulatory effect of diethylcarbamazine in mice infected with Nocardia brasiliensis

García-Hernández, Marisela; Castro-Corona, M Ángeles; Segoviano-Ramírez, J C; Brattig, Norbert W.; Garza, Carlos E. Medina-De la

doi:10.1016/j.intimp.2014.08.004

Cited by 13 publications

(8 citation statements)

References 23 publications

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“…Increase in lymphocytes in treated rats might have been due to the proliferation and transformation of lymphocytes in plasma cells which secrete antibody to eliminate the parasite from infected rats. Similar increase in lymphocyte proliferation was recorded in mice infected with Nocardia brasiliensis when treated with DEC [32]. …”

Section: Discussionsupporting

confidence: 74%

Immunopathological response of leukocytes against microfilariae and adult worms in white rats infected with Setaria cervi

Kausar¹,

Khan²

2017

Vet World

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Aim:Aim of this study was to see the immunopathological changes against the microfilariae (Mf) and adult worms of a bovine filarid, Setaria cervi in the tissues of vital organs of experimentally infected white rats. The effect of diethylcarbamazine (DEC) was also observed on the Mf, as leukocytes especially lymphocytes produce immunoglobulins which opsonize and increase the efficacy of DEC against circulating Mf. Effect of this drug was also assessed on liver enzymes in the microfilaremic rats.Materials and Methods:Microfilaremia was established by implanting adult worms intraperitoneally and by the infusion of Mf recovered from the uterus of gravid female worms. DEC was administered orally for six consecutive days in the rats having patent infection. Differential leukocyte count was recorded every 3rd day, and liver enzymes were estimated every 10th day in both treated and untreated rats. Pathological changes were observed in HE stained sections of vital organs where Mf or adult worms were trapped.Results:Destruction and reduction in microfilarial density were noticed in microfilaremic rats treated with DEC. Trapped Mf and embedded worms revealed heavy cellular infiltrations by defensive cells which surrounded and attached with the body surface of the Mf as well as adult worms for their destruction and piece meal clearance. Immune-mediated pathology was observed in the tissue sections of lungs, spleen, and liver. Liver enzymes were elevated during the period of higher parasitemia.Conclusions:There was a moderate level of immunopathology against the Mf and adult worms by the leukocytes in experimentally infected microfilaremic rats. Mf were in the process of degeneration where they got trapped. Moderate increase in liver enzyme was noticed which was slightly more in untreated group. Although a fraction of Mf gets killed in the peritoneum, majority of them successfully enter the systemic circulation and survive for about 54 days, which is sufficient enough for conducting immunological and chemotherapeutic studies.

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Section: Discussionsupporting

confidence: 74%

Immunopathological response of leukocytes against microfilariae and adult worms in white rats infected with Setaria cervi

Kausar¹,

Khan²

2017

Vet World

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“…Possible role of oxidative stress has been implicated as the major proposed mechanism of the antimicrobial effect by these agents 20 . Interestingly, as mentioned before the most popular postulate about the rationale of DEC involves the promotion of host inflammatory response 21 . Such impact is mainly associated with oxidative mechanism 22 .…”

Section: Discussionmentioning

confidence: 99%

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2016

IJPSR

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Objective: Following World Health Organization tropical disease research mandate, there is definitive need for search of new lead molecules for development of drug against human lymphatic filariasis. Thiazolidineone derivatives has shown versatile therapeutic potential. The present study has been undertaken to explore the possible antifilarial effect of such synthetic compounds against filarial parasite, Brugia malayi. Methods: A series of 12 thiazolidineone derivatives, following synthesis and characterization, were screened for antifilarial potential in vitro against microfilarial stage of Brugia malayi; those showed significant effect were tested against adult parasites also. The pharmacological response in terms of loss of parasitic motility was assessed under microscope. Further dose dependent response and potential lethality onto host cells for such effective drugs were carried out. Result: Out of the tested compounds, four such compounds showed significant activity and those were tested against the adult worms; one of these compounds showed marked effect. The corresponding IC 50 and LD 50 values were deduced for each of these four effective compounds. Most of them showed a good therapeutic index. Conclusion: Since the standard drug Diethyl Carbamazine Citrate is largely dependent on the host innate immune response and also not effective as microfilaricidal, hence the observed result with that thiazolidineone compounds have definitive potential for being considered as important therapeutic lead molecules against both microfilarial as well as the adult stage of the parasite.

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“…Several environmental and biologically active compounds such as medicinal plant extract and agrochemical pesticides 33,34 markedly and profoundly affected the immune response. Fungicides which are heterogeneous class of pesticides widely used in controlling agricultural industry and infectious diseases have been reported to be associated with immune alterations 35 . The exposure to these environmental chemicals caused either an immune hyperactivation resulting in autoimmunity or an immune alteration leading to immunosuppression 36 .…”

Section: Discussionmentioning

confidence: 99%

N‐acetylcysteine reduced the immunotoxicity effects induced in vitro by azoxystrobin and iprodione fungicides in mice

Naasri

Helali

Aouni

et al. 2020

Environmental Toxicology

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Azoxystrobin (AZO) and Iprodione (IPR) fungicides are extensively used worldwide, and therefore, contaminate all environmental compartments. The toxicity and the mechanisms by which they affected immune cells are complex and remain unknown. This study investigated the impact of AZO and IPR on the in vitro function of mice peritoneal macrophages including lysosomal enzyme activity and tumor necrosis factor (TNF)α and nitric oxide (NO) production in response to lipopolysaccharide (LPS) stimulation, the proliferation of mice splenocytes stimulated by concanavalin (Con)A and LPS, and the production of the Th1cytokine interferon‐gamma (IFNγ) and the Th2 cytokine interleukin (IL)‐4 and IL‐10 by ConA‐activated splenocytes. This is the first report indicating that AZO and IPR fungicides dose‐dependently inhibited mice macrophage lysosomal enzyme activity and LPS‐stimulated production of TNFα and NO. Mitogen‐induced proliferation of mice splenocytes was also suppressed by AZO and IPR in a dose‐dependent manner. More pronounced impact was observed on ConA‐induced response. The production of IFNγ by ConA‐stimulated splenocytes was dose‐dependently inhibited; however, the production of IL‐4 and IL‐10 increased in the same conditions. These results suggested that AZO and IPR polarized Th1/Th2 cytokine balance towards Th2 response. Overall, marked immunosuppressive effects were observed for AZO. The immunomodulatory effects caused by AZO and IPR were partially reversed by the pharmacological antioxidant N‐acetylcysteine (NAC), suggesting that both fungicides exerted their actions through, at least in part, oxidative stress‐dependent mechanism. Collectively, our data showed that AZO and IPR fungicides exerted potent immunomodulatory effects in vitro with eventually strong consequences on immune response and immunologically based diseases.

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Immunomodulatory effect of diethylcarbamazine in mice infected with Nocardia brasiliensis

Cited by 13 publications

References 23 publications

Immunopathological response of leukocytes against microfilariae and adult worms in white rats infected with Setaria cervi

Immunopathological response of leukocytes against microfilariae and adult worms in white rats infected with Setaria cervi

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N‐acetylcysteine reduced the immunotoxicity effects induced in vitro by azoxystrobin and iprodione fungicides in mice

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