ABSTRACT
Background Metabolic diseases are associated with impaired renal function which accelerates chronic kidney disease (CKD) progression. The aim of this study was to investigate the effects of 16-week honey supplementation on renal function, metabolic acidosis and renal abnormalities in Wistar rats fed a high-fat diet (HFD). Methods Wistar rats were fed a HFD and sucrose (30%) solution and randomly grouped and treated. Group 1 was fed rat chow and treated with drinking water while groups 2, 3, 4 and 5 were fed a HFD and treated with drinking water, 1, 2 and 3 g/kg body weight (BW) of honey, respectively, once daily for 16 weeks. After the rats were sacrificed, the serum samples were obtained and used for the analysis of total cholesterol, urea, creatinine, sodium, potassium, calcium, bicarbonates and chloride ions. Histopathological examinations of the kidneys were performed. Results The serum creatinine and anion gap levels were significantly (p < 0.01) higher while the levels of serum total calcium and ionized fraction were significantly (p < 0.01) lower in HFD-fed control rats than in chow-fed rats. The kidney of HFD-fed control rats was characterized by tubular necrosis, glomerular atrophy, hemorrhage and severe focal aggregate inflammatory (FAIC) cells. Honey treatment (1, 2 or 3 g/kg BW) prevented elevations in serum creatinine while it restored serum levels of total calcium and ionized calcium towards those in rats fed chow only. All the three doses of honey also significantly (p < 0.01) reduced anion gap and ameliorated renal lesions. Honey treatment (2 g/kg BW) significantly (p < 0.05) increased bicarbonate and chloride ion in HFD-fed rats compared with HFD-fed control rats. Conclusions Sixteen-week honey supplementation ameliorates renal dysfunction, metabolic acidosis and renal morphological abnormalities in HFD-fed Wistar rats.
ABSTRACT
BACKGROUND: Trypanosome infections still pose severe health and economic consequences, especially in the endemic regions of Sub-Saharan Africa. Trypanosome differentiation to the procyclic forms which lack the immune evasion mechanisms for survival in the bloodstream is prevented by tyrosine dephosphorylation which is catalyzed by protein-tyrosine phosphatase; thereby promoting survival of the parasites in the host. Inhibition of Protein-tyrosine phosphatase is a strategic therapeutic target that could attenuate trypanosomiasis. This study investigated the in vitro inhibitory effect of stem bark extracts of Khaya senegalensis and Tamarindus indica on the enzymatic activity of protein-tyrosine phosphatase. METHODS: All determinations were carried out following standard procedures for analytical experiments. The analogues of myristic acid that inhibited the enzymatic activity of protein-tyrosine phosphatase were isolated by bioassay-guided fractionation of stem bark extracts of Khaya senegalensis and Tamarindus indica. RESULTS: Analogues of myristic acid proved to be potent inhibitors of protein-tyrosine phosphatase. Double reciprocal (Lineweaver-Burk) plots of the initial velocity data indicated non-competitive inhibition with Ki of 0.67 mg/mL for Khaya senegalensis and 2.17 mg/mL for Tamarindus indica. The kinetic parameters for the cleavage of para-nitrophenylphosphate by the enzyme showed a KM of 3.44 mM and Vmax of 0.19 µmol/min. Sodium orthovanadate, the enzymes' specific inhibitor, inhibited the enzyme competitively with Ki of 0.20 mg/mL. Gas chromatography-mass spectrometry analysis of the stem bark bioactive fractions of Khaya senegalensis and Tamarindus indica revealed the presence of myristic acid analogues. CONCLUSION: Analogues of myristic acid are potent inhibitors of protein-tyrosine phosphatase that could be developed as trypanocide to inhibit the enzymatic activity of protein-tyrosine phosphatase in order to prevent transmission of trypanosomes.
