Effects of Aqueous Extract of Some Selected Vegetables on Halofantrine Hepato-cardiatoxicity in Rats.

Aim: The protective effect of some selected vegetables {Moringa (Moringa oleifera), Cabbage (Brassica oleracea) and Tomato (Solanum lycopersicum)} against hepatocardio toxicity of halofantrine (an antimalarial drug) was evaluated in 72 albino rats. Study Design: The rats were grouped into eight of nine rats each. Three different doses; 7.1, 14.2 and 21.3mg/Kg of halofantrine were given to group II, III and IV respectively. Group V was co-administered with halofantrine and moringa extract 7.1 and 0.20mg/Kg respectively, Group VI co-administered with halofantrine and cabbage extract 7.1 and 0.10mg/Kg respectively, Group VII co-administered with halofantrine and Tomato extract 7.1 and 0.20mg/Kg respectively and Group VIII co-administered with halofantrine, moringa, cabbage and tomato extracts 7.1, 0.20, 0.10 and 0.20mg/Kg respectively). Group I was neither given the drug nor the vegetable extract serving as normal control. Methodology: The liver and heart function indices were evaluated using standard methods. Results: Serum liver enzymes, heart marker enzymes and concentration of malondialdehyde (MDA) were analyzed after 16, 96 and 192 hours of oral administration. Halofantrine administration caused significant increase (p<0.05) in the activities of all the enzymes with a peak at the 16th hour. Malondialdehyde had a peak at the 192 hours. The oral co-administration of vegetables extract showed a significant decrease (p<0.05) in the enzyme activities and concentration of malondialdehyde as compared sole administration of halofantrine. The result showed that Moringa, Cabbage and Tomato may have hepato and cardio protective effects against halofantrine toxicity. It may be concluded that consumption of vegetables may be beyond the nutritional needs but also for protective purposes.

Effect of Ketoconazole, a Cytochrome P450 Inhibitor, on the Efficacy of Quinine and Halofantrine against Schistosoma mansoni in Mice

The fear that schistosomes will become resistant to praziquantel (PZQ) motivates the search for alternatives to treat schistosomiasis. The antimalarials quinine (QN) and halofantrine (HF) possess moderate antischistosomal properties. The major metabolic pathway of QN and HF is through cytochrome P450 (CYP) 3A4. Accordingly, this study investigates the effects of CYP3A4 inhibitor, ketoconazole (KTZ), on the antischistosomal potential of these quinolines against Schistosoma mansoni infection by evaluating parasitological, histopathological, and biochemical parameters. Mice were classified into 7 groups: uninfected untreated (I), infected untreated (II), infected treated orally with PZQ (1,000 mg/kg) (III), QN (400 mg/kg) (IV), KTZ (10 mg/kg)+QN as group IV (V), HF (400 mg/kg) (VI), and KTZ (as group V)+HF (as group VI) (VII). KTZ plus QN or HF produced more inhibition (P<0.05) in hepatic CYP450 (85.7% and 83.8%) and CYT b5 (75.5% and 73.5%) activities, respectively, than in groups treated with QN or HF alone. This was accompanied with more reduction in female (89.0% and 79.3%), total worms (81.4% and 70.3%), and eggs burden (hepatic; 83.8%, 66.0% and intestinal; 68%, 64.5%), respectively, and encountering the granulomatous reaction to parasite eggs trapped in the liver. QN and HF significantly (P<0.05) elevated malondialdehyde levels when used alone or with KTZ. Meanwhile, KTZ plus QN or HF restored serum levels of ALT, albumin, and reduced hepatic glutathione (KTZ+HF) to their control values. KTZ enhanced the therapeutic antischistosomal potential of QN and HF over each drug alone. Moreover, the effect of KTZ+QN was more evident than KTZ+HF.

Evaluation of biochemical indices following administration of artemether, halofantrine and a combination of artemether and lumefantrine in guinea pigs.

Combination of artemether and lumefantrine (artemether-lumefantrine) is an orally effective artemisinin-based combination therapy, used widely in the treatment of Plasmodium falciparum infections. The present study investigates the comparative effects of artemether, halofantrine and artemether-lumefantrine on biochemical indices in the male guinea pig. Half, normal and double therapeutic doses of the drugs were given to different groups of animals (n=5) by oral gavage. After the drug treatments, serum levels of biochemical parameters were measured using standard methods. Artemether significantly (p<0.05) reduced uric acid (UA) level (10.44%), but produced no significant effects on the other parameters measured. Halofantrine and artemether-lumefantrine significantly increased acid phosphatase- ACPT (56.13 and 26.45%) and prostatic acid phosphatase-ACPP (100.00 and 78.95%) respectively, while alkaline phosphatase (ALP) was not affected. In addition, halofantrine and artemether-lumefantrine significantly and dose-dependently decreased UA, while urea and creatinine levels were increased. UA was decreased by 12.15 and 17.92%; urea was increased by 84.42 and 53.25%; and creatinine was increased by 42.15 and 30.25%, respectively. Furthermore, both drugs had no significant effects on serum levels of total protein and cholesterol. The results show that halofantrine and artemether-lumefantrine may cause toxicity to renal and reproductive functions in the male guinea pig, halofantrine likely to cause more of these effects.

The Effect of Halofantrine in the Treatment of 14 Cases of Chloroquine Resistant Imported Malaria / 대한내과학회지

OBJECTIVES: The prevalence of malaria is increasing in recent years and also multidrug resistant malaria is increasing around the world and there is an increasing concern about imported malaria in nonendemic areas. Now many drugs are tried to find out effect on multidrug resistant malaria. We performed this study to investigate the thrapeutic effect of halofantrine in the treatment of chloroquine resistant imported malaria. METHODS: From Feb. 1992 to May 1995, we experienced 35 patients infected with malaria and treated 14 patients among 35 patients with halofantrine. RESULTS: 1) All 14 patients were sailor with a mean age of 39.4 years and infected with malaria. 2) The majority of patients were infected with malaria at Africa. 3) 10 patients were infected with Plasmodium falciparum and the remainder were undetermined. 4) In the 11 cases of chloroquine resistant malaria treated with quinine plus tetracycline combination therapy or Fansidar, 4 cases could not be tolerable due to side effects and resistance to the therapy, we substituted halofantrine for above regimens. 5) In the 10 cases, treated after May 1994, halofantrine was the first choice of treatment because they were the cases of malaria infected in the mid-Africa where the prevalence of chloroquine resistant malaria is high. 6) With halofantrine, all 14 cases were treated with minimal side effects suc4 as nausea, vomiting, anorexia, abdominal pain and fatigue. CONCLUSION: We think halofantrine is a simple and effective regimen against chloroquine resistant malaria and consider this agent as an alternative therapeutic regimen on chloroquine resistant malaria.