Investigating the Comparative Effects of Six Artemisinin-based Combination Therapies on Plasmodium-induced Hepatorenal Toxicity.

BACKGROUND: Too many artemisinin-based combination therapies (ACTs) are available, thus creating a dilemma on the most preferred for the treatment of malaria. AIM: We compared the effect of six ACTs in mitigating Plasmodium-induced hepatorenal toxicity in experimental malaria. MATERIALS AND METHODS: Forty adult male Swiss mice allotted into eight groups: Group 1 (normal control [NC] uninfected and untreated), Group 2 (parasitized nontreated - [PNT]), and Groups 3-8 received Plasmodium berghei inoculum. After 72 h, the initial parasitemia was established. Groups 3-8 were administered oral therapeutic doses of artesunate-amodiaquine (AA), artesunate-mefloquine (AM), artesunate-sulfadoxine-pyrimethamine (ASP), artemisinin-piperaquine (AP), dihydroartemisinin-piperaquine (DP), and artemether-lumefantrine (AL) per kg bodyweight, respectively, as standard regimen, and final parasitemia determined. Animals were euthanized via chloroform inhalation and blood collected for hepatorenal analysis. Liver and kidney were dissected out for histology. RESULTS: Parasitemia was significantly (P < 0.05) decreased in tests compared to PNT, except in ASP group. Liver enzymes were significantly (P < 0.05) increased in PNT compared to tests and NC. Hyperplastic cells and portal tract inflammation were prominent in ASP group, but mild to moderate in other treated groups. Urea-creatinine were significantly (P < 0.05) increased in PNT compared to treated groups. The Na+ and Cl- were significantly (P < 0.05) reduced in PNT, with significantly (P < 0.05) increased K+ compared to NC and treated groups. Glomerulonephritis and glomerulus splitting was observed in PNT, while moderate distortions were observed in treated groups. The AA and AM groups had good kidney histoarchitecture. CONCLUSION: Parasitemia decreased in all the treatment groups except in PNT and ASP groups which had severe hepatorenal distortions. Hepatorenal histoarchitecture were mildly distorted in the AA, AM and AL-administered groups with lower hepatorenal indices comparable to NC. The least elevated liver enzymes were in AA and AM. In decreasing order ASP > DP > AL > AP > AM > AA.

Evaluation of in vivo antimalarial activities of ethanolic leaf and seed extracts of Telfairia occidentalis.

The leaves and seeds of Telfairia occidentalis are used as vegetables in making soups in Southern Nigeria. In this study, we investigated the antimalarial activity of leaf and seed extracts in vivo in mice infected with Plasmodium berghei berghei during early and established infections. T. occidentalis leaf extract (250-750 mg/kg/day) exhibited antiplasmodial activity both in the 4-day early infection test and in established infection with a marked increase of the mean survival time, which, however, remained lower than that achieved with the standard drug, chloroquine (5 mg/kg/day). The seed extract (450-1,350 mg/kg/day) also demonstrated a promising blood schizontocidal activity in early and established infections. This plant possesses significant antiplasmodial activities, which may be exploited in the control of malaria.

Effects of the fruit of Telfairia occidentalis on some biomolecules in rat.

The effects of the ethanolic fruit extract of T. occidentalis on some enzymes and biochemical parameters were evaluated in rats. 100, 500 and 1000 mg kg(-1) of the extract were administered orally and once daily to three different groups of rats, respectively, for 28 days. The fourth group which served as control received distilled water only. On the 29th day, the rats which had been fasted overnight were dissected under chloroform anaesthesia and blood was collected directly from their hearts. The blood was allowed to clot and centrifuged to obtain the serum which was kept in a refrigerator at -4 degrees C until used for analysis. Appropriate Commercial kits (Randox Laboratories, U.K.) were used to evaluate the serum activity or concentration of the following parameters:alanine and aspartate transaminases, alkaline phosphatase, cholesterol, triglycerides, creatinine, high density lipoproteins, total and conjugated bilirubin and total proteins. The fruit extract of the plant significantly elevated the serum concentrations of cholesterol, triglycerides, total proteins, at the three dose levels. The 500 and 1000 mg kg(-1) doses increased the concentrations of HDL and conjugated bilirubin. While only 100 and 500 mg kg(-1) doses of the extract reduced the level of total bilirubin. The hypercholesterolemic, hyperproteinemic, hypertriglyceridemic and hyper conjugated bilirubinemic effect of this extract coupled with the increased activity of alkaline phosphatase suggest that the fruit of Telfaira occidentalis may not be safe for consumption. This is quite contrary to the nutritional usage of the leaf and seed of this plant.

Hypoglycemic effect of the seed extract of Telfairia occidentalis in rat.

The blood glucose lowering effect of the ethanolic extract of the seed of Telfaria occidentalis in normoglycemic, alloxan-diabetic and glucose loaded rats was determined. Ethanolic extract of the seed of Telfairia occidentialis was administered at two dose levels (100 and 250 mg kg(-1)) to both normoglycemic and alloxan diabetic Wilstar albino rats. Blood was collected from the tail vein of the rats at 1, 2 and 4 h. Oral Glucose Tolerance Test (OGTT) was carried out by administering 100 and 250 mg kg(-1) of the extract to glucose loaded rats (1 g kg(-1)) and blood was collected from the tail vein of rats at 0, 15, 30, 45 and 60 min. Blood glucose level was determined using a glucometer. Standard methods were used for phytochemical screening of the extract. The results showed that 100 mg kg(-1) ethanolic extract of seed of T. occidentalis reduced blood glucose concentration significantly only in the alloxan diabetic and not in the normoglycemic rats. 250 mg kg(-1) extract did not show this effect. The extract did not affect the oral glucose tolerance of rats when administered simultaneously or 1 h before glucose loading. Phytochemical screening indicated the presence of alkaloids, steroids, tannins and terpenes. It could be concluded that the ethanolic extract of the seed of Telfairia occidentalis possesses hypoglycemic effect in alloxan diabetic rats and could be useful in the ethnotherapy of type 2 diabetes.