Clinical Probe of Cyp2C8*2 Mutants in a Malaria Hyperendemic Zone: Evidence from North-Central, Nigeria.

BACKGROUND: A tremendous level of success has been achieved since the introduction of chloroquine and the combination of amodiaquine and artemisinin for the treatment of both complicated and uncomplicated malaria infections in sub-Saharan Africa. However, the recent discovery of drug resistant strains of Plasmodium falciparum (P.f.) and the ability of the parasite to ingest CYP2C8 into its digestive vacuole is of great public health concern. This study probes the occurrence of CYP2C8*2 allelic mutant amongst malaria patients in North-Central Nigeria. METHODS: Three hundred and eighty five (385) unrelated study participants were screened for current malaria episodes using routine microscopy and/or rapid diagnostic test strips (RDTs). Chelex extraction method was used for single nucleotide polymorphisms (SNPs) and identification of CYP2C8*2 (805A > T) variant respectively. Wild-type (A) and the defective allele (T) were differentiated with the use of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The results obtained were further validated with Sanger sequencing of a few samples and thereafter, the genotype data were statistically processed. All alleles obtained were in Hardy Weinberg equilibrium. RESULTS: Out of the 385 participants (45.5% Male and 54.5% Female) genotyped for SNPs, 75 (19.5%) had the autosomal recessive mutant trait. Occurrence of mutant traits was gender and ethnic independent (p > 0.05). Yoruba ethnic group recorded a reduction in proportion of genotypic defective CYP2C8*2 allele (T) (1 in every 8 persons) with a carrier percentage of 13.3% compared with Hausa (26.62%); Igbo (25.37%) and other minority ethnic groups (17.6%). CONCLUSIONS: A remarkable inter-ethnic differences in autosomal recessive CYP2C8*2 allele was observed. By implication, there is a gradual incursion of genetic drift for poor CQ and AQ-Artemisinin metabolizers among the inhabitants.

Alterations in histological, biochemical and hematological parameters in Plasmodium berghei NK-65 infected balb/c mice treated with Bridelia ferruginea stem bark extract.

BACKGROUND: Recent ethnomedicinal studies on Bridelia ferruginea Benth (family Phyllanthaceae) as an antiplasmodial remedy have established its potency as a strong prophylactic and chemosuppressive agent. Human consumption of medicinal herbs without adequate evaluation of its efficacy and safety can result in grave physiological and pathological consequences. Therefore, this study assessed the antiplasmodial bioactivity, biochemical, hematological, histopathological and toxicity profile of the ethanolic stem bark extract of B. ferruginea in mice. METHODS: Ethanolic stem bark extract of B. ferruginea (200, 400 and 800 mg/kg) were orally administered to Plasmodium berghei-infected mice in models and were subsequently observed for mortality, behavioral changes and signs of toxicity. Acute evaluation was experimented at 1,000 mg/kg for 28 days. Occult blood obtained from the euthanized mice were subjected to biochemical and hematological assays. A comprehensive assessment of the histology of the liver and kidney was also ascertained. The median lethal dose (LD50) was determined and extrapolated using the regression equation obtained from the plot of the probits of mortalities (y) and the log of doses (log10C). RESULTS: Different concentrations of the phytochemical secondary metabolites were revealed. Antiplasmodial bioactivity was established at the 200, 400 and 800 mg/kg of the herbal extract with a dearth in parasitemia at different days post-treatment. The 800 mg/kg group responded by exhibiting a dose-dependent decrease in parasitemia comparable with the chloroquine bi-phosphate group. Significant alterations in the histology of the liver and kidney of the 1,000 mg/kg group was documented. There was a reduction in the titers of LDH, ALT, AST, and urea in the treated group when compared with the control (p < 0.05). Antioxidant profiles were also highly significant with elevation in SOD, GPx, and CAT, but a reduction in MDA. LD50 was established at 424 mg/kg. CONCLUSION: B. ferruginea Benth (family Phyllanthaceae) is a potent antiplasmodial, antioxidant, regenerative and ameliorative herbal remedy if administered in controlled dosage.