Inhibition Of Nitric Oxide Synthesis By Dexamethasone Increases Survival Rate In Plasmodium berghei-Infected Mice

Abstract

20Malaria still presents great epidemiologic importance by its high incidence in the 21 world and potential clinical severity. Plasmodium parasites are highly susceptible to 22 changes in the redox balance and the relationship between the redox state of the 23 parasite and host cells is very complex and involves nitric oxide (NO) synthesis. 24Thus, the present study is aimed at evaluating the effects of NO synthesis on the 25 redox status, parasitemia evolution and survival rate of Plasmodium berghei-26 infected mice. Two-hundred and twenty-five mice were infected with Plasmodium 27 berghei and submitted to the stimulation or inhibition of NO synthesis. The 28 stimulation of NO synthesis was performed through the administration of L-29 arginine, while its inhibition was made by the administration of dexamethasone.30 Inducible NO synthase (iNOS) inhibition by dexamethasone promoted an increase 31 in the survival rate of P. berghei-infected mice and data suggested the participation 32 of oxidative stress in brain as a result of plasmodial infection, as well as the 33 inhibition of brain NO synthesis, which promoted survival rate of almost 90% of the 34 animals until the 15 th day of infection, with possible direct interference of ischemia 35 and reperfusion syndrome, as seen by increased levels of uric acid. Inhibition of 36 iNOS caused a decrease of parasitemia and increased survival rate of infected 37 animals, suggesting that the synthesis of NO may stimulate a series of 38 compensatory redox effects that, if overstimulated, may be responsible for the 39 onset of severe forms of malaria. 40 Plasmodium berghei, Inducible nitric oxide synthase, parasitemia, survival rate. 42 43 93Moreover, in response to the infection, activated macrophages and 94 neutrophils act as the natural defense mechanism of the host organism and these 95 generate a large amount of free radicals by activation of respiratory burst, causing 96 an imbalance between the formation of oxidant species and the activity of 97 antioxidants. This imbalance triggers the oxidative stress, being an important 98 mechanism of human host in response to microbial infections that, in the case of 99 malaria, can lead to the death of parasites.

Molecular Docking Prediction and in Vitro Studies Elucidate Anti-inflammatory Effect of Garcinia Extract Against Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Targets

“…The H-bond formation together with the hydrophobic interactions indicates that garcinol as well as HCA other than the anti-in ammatory drugs could prove to be potent inhibitor of iNOS and COX-2. Studies have shown that anti-in ammatory drugs (NSAIDs) such as dexamethasone and indomethacin inhibit iNOS and COX-2 [5,52].…”

Molecular docking prediction and in vitro studies elucidate anti-inflammatory effect of Garcinia extract against inducible nitric oxide synthase and cyclooxygenase-2 targets

“…The H-bond formation together with the hydrophobic interactions indicates that Garcinol, as well as HCA other than the anti-inflammatory drugs, could prove to be a potent inhibitor of iNOS and COX-2. Studies have shown that anti-inflammatory drugs (NSAIDs) such as dexamethasone and indomethacin inhibit iNOS and COX-2 [5,81]. NSAIDs like sodium diclofenac and ibuprofen have shown interaction with iNOS with binding energy (ΔG) of about -6.7 kcal/mol and -7.50 kcal/mol, respectively [82,83].…”

The Role of Nitric Oxide in Regulating Intestinal Redox Status and Intestinal Epithelial Cell Functionality

“…These proteins include protein kinase C δ (PKC) [35,36] and c-Jun N-terminal kinase (JNK) [37,38,39]. In addition, other factors that regulate iNOS mRNA stability include transforming growth factor–β (TGF-β) [40,41], dexamethasone [42,43,44], 8-bromo-cyclic guanosine monophosphate (cGMP) [45,46], intracellular calcium elevating agents [47], forskolin (activates adenylate cyclase), dibutyryl cyclic adenosine monophosphate (cAMP) (membrane permeable cAMP analog) [48,49], tetrahydrobiopterin (BH4) [50,51], and L-arginine [52,53].…”