Effects of autacoid inhibitors and of an antagonist on malaria infection in mice

Abstract

The effects of p-chlorophenylalanine, an inhibitor of serotonin synthesis, indomethacin, an inhibitor of prostaglandin synthesis, cyproheptadine, a serotonin, bradykinin and histamine antagonist, were assessed separately and in combination with chloroquine (CQ) in Vom strains of Swiss albino mice (18-22 g) of either sex infected intraperitoneally with 1 x 10(7) Plasmodium yoelii nigeriensis-induced malaria. As prophylactic, these agents reduced from 31.9 +/- 4.5 to 16.1 +/- 8.1% the level of parasitemia relative to control but had no appreciable activity as curative agents when administered subcutaneously once daily for 4 days after 72 h of parasites innoculum in vivo. However, CQ alone and the combination of these agents with CQ in curative and prophylactic treatments significantly reduced (from 50.3 +/- 5.8 to 4.9 +/- 0.75%) the level of parasitemia (P< 0.05), which was taken only once 72 h after the parasites innoculum. The prophylactic result was shown to produce better results than the curative treatment. The data indicate that inhibitors and an antagonist can reduce the parasitemia load (the extent of damage and the severity of infection) as well as enhance the effects of CQ when combined with it for malaria therapy. The study reveals that the production of autacoids in established infection renders autacoid inhibitors and an antagonist ineffective for radical cure in malarial mice; however, selective inhibition of local hormones implicated in the pathological manifestations of malaria infection by autacoid inhibitors and an antagonist may be a possible pathway to reduce the severity of infection and the associated tissue damage and to enhance the efficacy of available anti-malarials.

Immunotherapeutic Potential of Plasmodium Against Cancer by Inducing Immunomodulation

“…It has been acknowledged that most of the trials that have been performed were on rodents that shows ofcourse great similarity with human but certain complications were observed such as, there was no fever suffering (Hyperthermia) due to malaria in rodents unlike human [70] and the antitumor effects are more long-lasting in rodents, upto a month, which illustrates that infectious period is directly proportional to the effect on tumor growth inhibition. While the benign malaria in human was observed to cause hyperthermia at acute phase and the malaria parasite could survie for years in chronic stages if the treatment is not provided.…”

Inflammation: the foundation of diseases and disorders. A review of phytomedicines of South African origin used to treat pain and inflammatory conditions.

“…The importance of cytokines in disease has been illustrated in studies by Iwalewa and Agbani (2004) and Iwalewa et al (2007) (submitted paper). These studies were conducted to inhibit the autacoids released before and during malaria infection and diabetes disorders respectively.…”

“…The molecular mechanism of chronic inflammation, its prevention and mitigation with phytomedicines have been intensively evaluated by our group over the past ten years (McGaw et al, 1997;Eloff et al, 2001;McGaw et al, 2001;Iwalewa et al, 2003;Omisore et al, 2004;Iwalewa and Agbani, 2004;Iwalewa et al, 2005;Omisore et al, 2005;Iwalewa et al, 2006;Idowu et al, 2006;Naidoo et al, 2006;Angeh et al, 2007). Epidemiological data suggest that lower incidences of certain chronic dis-*Corresponding author.…”