Immune effector mechanisms of the nitric oxide pathway in malaria: cytotoxicity versus cytoprotection

Nahrevanian, Hossein

doi:10.1590/s1413-86702006000400014

Cited by 19 publications

(19 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is suggested that the detrimental effect of NOS is related to the L-arginine and NO concentrations, because NO at high concentration has a clear anti-inflammatory effect [139][140][141][142]. Thus, activation of NO could be a potential therapeutic strategy to suppress parasitic infections [143][144][145]. Nevertheless, the functional role of NO and NOS isoforms in the immune responses of host against the majority of parasites is still highly controversial.…”

Section: Conclusive Remarksmentioning

confidence: 99%

Involvement of nitric oxide and its up/down stream molecules in the immunity against parasitic infections

Nahrevanian

2009

Braz J Infect Dis

Self Cite

View full text Add to dashboard Cite

Nitric oxide (NO) is a potent mediator with diverse roles in regulating cellular functions and signaling pathways. The NO synthase (NOS) enzyme family consists of three major isoforms, which convey variety of messages between cells, including signals for vasorelaxation, neurotransmission and cytotoxicity. This family of enzymes are generally classified as neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Increased levels of NO are induced from iNOS during infection; while eNOS and nNOS may be produced at the baseline in normal conditions. An association of some key cytokines appears to be essential for NOS gene regulation in the immunity of infections. Accumulating evidence indicates that parasitic diseases are commonly associated with elevated production of NO. NO plays a role in the immunoregulation and it is implicated in the host non-specific defence in a variety of infections. Nevertheless, the functional role of NO and NOS isoforms in the immune responses of host against the majority of parasites is still highly controversial. In the present review, the role of parasitic infections will be discussed in the controversy related to the NO production and iNOS gene expression in different parasites and a variety of experimental models.

show abstract

Section: Conclusive Remarksmentioning

confidence: 99%

Involvement of nitric oxide and its up/down stream molecules in the immunity against parasitic infections

Nahrevanian

2009

Braz J Infect Dis

Self Cite

View full text Add to dashboard Cite

show abstract

“…As L-Arg has long been identified as an essential amino acid for Leishmania growth, promastigotes could not be maintained in L-Arg-free media (Krassner and Flory, 1971), suggesting mechanisms of L-Arg uptake and utilization in Leishmania parasites (Shaked-Mishan et al, 2006). This study is a continuous research of authors previous publications (Nahrevanian, 2004(Nahrevanian, , 2006Nahrevanian and Amini, 2009;Nahrevanian et al, 2006Nahrevanian et al, , 2008Nahrevanian et al, , 2009a2009b). Therefore, the aim of this study is to investigate the partial immunotherapy of leishmaniasis by in vivo trial of L-Arg in Balb/c mice infected with Leishmania major via nitric oxide pathway.…”

Section: Introductionmentioning

confidence: 81%

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

View full text Add to dashboard Cite

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.

show abstract

“…Increased levels of NO were found to be beneficial, as NO was shown to kill parasites (Gyan et al, 1994;Rockett et al, 1991). The LPS are believed to be potent inducers of macrophage ROI and RNI against a variety of intracellular and extracellular pathogens and to be potent stimulators of NOS isoforms (Nahrevanian, 2006). The synthetic glucocorticoid DEX has been reported to inhibit iNOS induction, which may contribute to its inflammation-reducing effects (Orazizadeh et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Najafi et al (2015) used the same LPS to stimulate the immune system in inbred balb/c mice and they found that LPS stimulates the immune system did not increase NO levels in this species of mice (Najafi et al, 2015). Nahrevanian (2006) applied the same LPS to stimulate the immune system in outbred NMRI mice and they observed that LPS stimulates the immune system and increase NO levels in this species of mice . Scheller et al (1997) and Klotz et al (1995) used DEX in several studies as a specific inhibitor of the immune system by reducing of cellular and humoral defense in preventing various diseases (Klotz et al, 1995;Scheller et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Immunobiochemical Study of Host During Malaria Infection via Nitric Oxide Pathway after Modulation by Lipopolysaccharide and Dexamethasone in Mice Model

Modaresine¹,

Nahrevania²,

Khatami³

2015

International J. of Biological Chemistry

View full text Add to dashboard Cite

Malaria is a parasitic disease which is common in tropical and subtropical regions of the world. Lipopolysaccharide (LPS) as an inducer and dexamethasone (DEX) as an inhibitor of the immune system are used in this study. The LPS and DEX effects on the level of nitric oxide (NO) of plasma, liver and spleen, hepatomegaly, splenomegaly, survival rate and the degree of parasitaemia on malaria infected mice were investigated. In this study, 24 outbred mice were randomly divided into 4 groups of 6 animals. Entire mice were infected by the murine malaria parasite Plasmodium berghei. Two groups of mice were selected as controls, which were injected with intraperitoneal (ip) injection of normal saline. The two DEX and LPS groups of mice had received concentrations of 4 and 1 mg kgG 1 treatment respectively by 8 times ip injection every other day. Their body weight, survival rates and parasitaemia were monitored during the study. Finally, mice were euthanized by terminal anesthesia and cardiac puncture and the entire liver and spleen were removed for hepatosplenomegaly. Plasma and liver/spleen suspensions were assessed for immunobiochemical alterations of NO levels. The results indicated an increase in hepatomegaly of test group compared to control mice. The LPS mice represented splenomegaly more than DEX one. Nitric oxide in plasma, liver and spleen in both DEX and LPS group was changed, however, the only significant difference was observed in the liver of LPS. It is concluded that LPS and DEX can be applied as a standard and medically approved inducer and inhibitor of the immune system respectively, for experimental immunomodulation studies in animal models. In this study, LPS induced and DEX reduced immune responses in mice during malaria infection by alterations and manipulation of immunobiochemical factors via NO pathway. This may lead to an immunotherapy trial of malaria by control the pathophysiology and degree of parasitaemia in mouse model.

show abstract

Immune effector mechanisms of the nitric oxide pathway in malaria: cytotoxicity versus cytoprotection

Cited by 19 publications

References 87 publications

Involvement of nitric oxide and its up/down stream molecules in the immunity against parasitic infections

Involvement of nitric oxide and its up/down stream molecules in the immunity against parasitic infections

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

Immunobiochemical Study of Host During Malaria Infection via Nitric Oxide Pathway after Modulation by Lipopolysaccharide and Dexamethasone in Mice Model

Contact Info

Product

Resources

About