Expression of inducible nitric oxide synthase (iNOS) mRNA in target organs of lethal and non‐lethal strains of murine malaria

Nahrevanian, Hossein; Dascombe, Michael J.

doi:10.1046/j.1365-3024.2002.00490.x

Cited by 21 publications

(11 citation statements)

References 36 publications

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“…Despite the fact that L‐arginine supplementation increased foetal viability, we did not observe any improvement in the elevation of HO‐1 and iNOS, two biomarkers of oxidative stress, upon L‐arginine supplementation. Both iNOS and HO‐1 are induced during production of NO and play integral roles in attenuating malaria pathogenesis . Thus, an increase in NO production should have increased the expression of these two markers in the liver, which we did not see in the dams receiving L‐arginine.…”

Section: Discussioncontrasting

confidence: 56%

Dysregulation of solute carrier transporters in malaria‐infected pregnant mice

Najjar

McColl

Weckman

et al. 2019

Parasite Immunology

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Summary Aims Malaria in pregnancy (MiP) alters the expression of ATP‐binding cassette efflux transporters in maternal and foetal tissues, as well as the placenta. Malaria induces oxidative stress, and pregnancy is associated with arginine deficiency. We hypothesized that reducing oxidative stress during MiP by supplementation with L‐arginine, a NO precursor, would attenuate transcriptional changes in a second superfamily of transporters, solute carrier (SLC) transporters, and improve pregnancy outcomes. Methods and Results Pregnant BALB/c mice receiving L‐arginine (1.2%) in water, or water alone, were infected with Plasmodium berghei ANKA on gestational day 13 and sacrificed on gestational day 19. Compared to controls, the mRNA of numerous SLC transporters was downregulated in maternal and foetal tissues, as well as in the placentas of infected mice. While supplementation with L‐arginine did improve foetal viability, it did not improve the mRNA expression of oxidative stress markers, transporters nor other indices of foetal and maternal health. Moreover, amino acid uptake transporters were downregulated upon infection, which could potentially contribute to decreased foetal birthweight. Conclusions Malaria in pregnancy significantly alters the expression of SLC transporters in maternal and foetal tissues as well as the placenta, regardless of L‐arginine supplementation. Further studies to investigate methods of reducing oxidative stress in MiP are warranted.

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Section: Discussioncontrasting

confidence: 56%

Dysregulation of solute carrier transporters in malaria‐infected pregnant mice

Najjar

McColl

Weckman

et al. 2019

Parasite Immunology

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“…55 In addition, during lethal P. berghei infection, inducible NOS mRNA levels in the liver decreased as parasitemia rose but then increased later in infection when mice were close to death. 56 Here, failure to clear parasites was associated with increased inducible NOS expression in the liver late during infection. In the context of the observed reduction in tissue pathology and increased PPARγ transcript levels, it is likely that decreased NOS expression in the liver and spleen of ABA-supplemented mice on day 7 of infection reflects recovery from inflammation.…”

Section: Discussionmentioning

confidence: 86%

Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission

Glennon¹,

Adams²,

Hicks³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Nearly half of the world's population is at risk for malaria. Increasing drug resistance has intensified the need for novel therapeutics, including treatments with intrinsic transmission-blocking properties. In this study, we demonstrate that the isoprenoid abscisic acid (ABA) modulates signaling in the mammalian host to reduce parasitemia and the formation of transmissible gametocytes and in the mosquito host to reduce parasite infection. Oral ABA supplementation in a mouse model of malaria was well tolerated and led to reduced pathology and enhanced gene expression in the liver and spleen consistent with infection recovery. Oral ABA supplementation also increased mouse plasma ABA to levels that can signal in the mosquito midgut upon blood ingestion. Accordingly, we showed that supplementation of a Plasmodium falciparum-infected blood meal with ABA increased expression of mosquito nitric oxide synthase and reduced infection prevalence in a nitric oxide-dependent manner. Identification of the mechanisms whereby ABA reduces parasite growth in mammals and mosquitoes could shed light on the balance of immunity and metabolism across eukaryotes and provide a strong foundation for clinical translation.

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“…The Griess reaction was adapted to assay nitrate as described previously (Nahrevanian and Dascombe, 2001, 2002, 2003. Briefly, standard curves for sodium nitrate (Sigma) were prepared and 100 µL samples were poured in microtubes, then 100 µL Griess reagent was added and proteins subsequently precipitated by 100 µL trichloroacetic acid (Sigma).…”

Section: Griess Micro Assay (Gma)mentioning

confidence: 99%

Partial Immunotherapy of Leishmaniasis by in vivo Trial of L-Arginine in Balb/c Mice Infected with Leishmania major via Nitric Oxide Pathway

Faezi¹,

Nahrevania²,

Farahmand³

et al. 2015

International J. of Biological Chemistry

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Leishmaniasis is a vector-borne disease in tropical and subtropical regions. It presents a wide spectrum of clinical manifestations; Cutaneous Leishmaniasis (CL) is the most common form leading to a skin nodule. L-Arginine (L-Arg) is an important amino acid involved in many metabolic pathways in host macrophages (MΦs) including NO synthesis. The L-Arg pathway is relevant to leishmaniasis due to its role in regulating MΦ functions. Activated MΦs can produce leishmaniacidal molecules, such as Nitric Oxide (NO) and oxidative mediators to kill parasite. Different concentrations of L-Arg were used; their toxicities assessed in naïve Balb/c mice. The highest concentration with lowest toxicity was selected to apply in Leishmania major infected mice. Test group was injected with three types of L-Arg (oral, local, injection) and control group received normal saline. Then, the lesion size, the measurement of amastigotes proliferation in MΦ, the pathophysiology of mice (hepato/spelenomegaly, survival rate, body weight) was all evaluated. In addition, plasma and tissue suspensions were investigated for NO induction using Griess Micro Assay (GMA). This is the first application of oral, local and injection forms of L-Arg against Iranian strain L. major MRHO/IR/75/ER. Results indicated L-Arg had ability to elevate NO in murine host. No pathological effects were observed in oral, local and injection types of L-Arg. Moreover, a significant decrease in parasite proliferation was observed only in oral group which presented anti-leishmanial activity by reduction liver and spleen positive smears. In injection form, percentage of positive smears was reduced only in spleen; a reduction observed in lesion sizes after treatment with oral and injection form of L-Arg; no significant alteration of local L-Arg to limit lesion size in CL was indicated here. The L-Arg is NO precursor and has been used safely for decades to treat physiological condition and used as food supplementary with no toxicity. In this study, L-Arg presented its partial ability to induce NO and treat animals. It also has limited potential therapeutic effects against CL by alteration of NO in host; therefore, it may be indicated solo as an anti-leishmanial agent or in a combination therapy for CL in mice. This may be the first immunotherapy trial against CL in Iran.

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Expression of inducible nitric oxide synthase (iNOS) mRNA in target organs of lethal and non‐lethal strains of murine malaria

Cited by 21 publications

References 36 publications

Dysregulation of solute carrier transporters in malaria‐infected pregnant mice

Dysregulation of solute carrier transporters in malaria‐infected pregnant mice

Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission

Partial Immunotherapy of Leishmaniasis by in vivo Trial of L-Arginine in Balb/c Mice Infected with Leishmania major via Nitric Oxide Pathway

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