Ashafa, A. O. T.O'Neill, F. H.Sabiu, Saheed2019-06-282019-06-282016-09http://hdl.handle.net/11660/9933The kidney is tasked with a number of metabolic functions in the body. In its role as a detoxifier and primary eliminator of xenobiotics, it becomes vulnerable to developing injuries. Currently, over 1 million people in the world are living on either of the renal replacement therapies (RRT). These therapies (dialysis and kidney transplantation) are highly sophisticated and generally unaffordable to the average income class and as such most of the patients of kidney disease are left to die because of non-availability of RRT facilities or their inability to afford it. Phytotherapy has emerged as a viable alternative and is being employed to protect renal function and delay progression of renal pathological conditions into end-stage where the last resort is RRT. Zea mays L. (Poaceae), Stigma maydis is one of several herbs that have been ethnomedicinally advocated to having the capability to improve renal function. This much touted claim was investigated by evaluating its extracts against acetaminophen (APAP)-mediated oxidative nephropathy using in vitro and in vivo experimental models. The in vitro study revealed that Z. mays, S. maydis is well tolerated by HEK293 cells (a human kidney cell line) and significantly (p<0.05) inhibited calcium oxalate nucleation crystals with the highest dose exhibiting 93.4% potency. This inhibitory effect of the extract had an overall half maximal concentration (IC50) of 256 μg/mL (R2= 0.9775) with corresponding significant reduction in the degree of turbidity of the treated crystal solution. While the effect elicited may be attributed to its saponin contents, its overall pharmacological effects in this study could in part also be ascribed to its antioxidant activity. These findings have lent credence to the ethnomedicinal significance of Z. mays, S. maydis as a candidate for the management of nephrolithiasis and renal dysfunctions. With nephropathy as one of the complications of diabetes, the inhibitory effect of Z. mays, S. maydis on the specific activities of carbohydrate metabolizing enzymes (α-amylase and α-glucosidase) was evaluated. The results showed that it exhibited potent and moderate inhibitory potential against α-amylase and α-glucosidase respectively. The inhibition in each case was concentration-dependent with respective IC50 values of 5.89 and 0.93 mg/mL. The extract also remarkably scavenged reactive oxygen species like DPPH and nitric oxide radicals, elicited good reducing power and significant metal chelating attributes. The respective uncompetitive and non-competitive nature of the extract on α-glucosidase and α-amylase activity suggests that the phytoconstituents in the extract either assuage substrate level which facilitated their binding and subsequent inhibition of α-glucosidase or bind to a site other than the active site of α-amylase/α-amylase-substrate complex. Consequently, this will reduce the rate of starch hydrolysis, enhance palliated glucose levels, and thus, lending credence to the hypoglycaemic activity of Z. mays, S. maydis. Following OECD guidelines for testing of chemicals and extracts, the safety of consumption of the extract was investigated on key metabolic organs of Wistar rats. It was found that at 5000 mg/kg body weight of the extract, no treatment-induced signs of toxicity, behavioural changes or mortality were observed in the animals. Thus, its median lethal dose was estimated to be above 5000 mg/kg. In the repeated dose toxicity study, treatment with the extract also revealed no significant (p>0.05) difference in haematological and clinical biochemistry parameters compared to the control group. Similarly, observations from the cage side produced no treatment-related signs of clinical toxicity and histoarchitectural changes. However, there was significant (p<0.05) increase in the body weight (22.31%), exploratory ability (28.68%) as well as white blood cell (71.58%) and platelet counts (63.82%) of the 500 mg/kg extract-treated animals compared with the control group. These observations are consistent with the non-toxic tendency of the extract and suggest that it may be labelled and classified as practically safe within the doses investigated and period of the study. The results of the role of Z. mays, S. maydis extract in hepatic biotransformation of APAP showed that, the APAP-induced significant (p<0.05) increases in the activities of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase and the concentrations of bilirubin, oxidized glutathione, protein carbonyls, malondialdehyde, conjugated dienes, lipid hydroperoxides and fragmented DNA were dose-dependently extenuated following treatment with the extract. The extract also significantly (p<0.05) improved the reduced activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase as well as total protein, albumin and glutathione concentrations in the treated hepatotoxic rats. These improvements may be attributed to the bioactive constituents as revealed by the GC-MS analysis of the extract. The observed effects compared favourably with vitamin C and are indicative of hepatoprotective and antioxidative attributes of the extract and were further supported by the histological analysis. The overall data from the study suggest that Z. mays, S. maydis is capable of preventing and ameliorating APAP-mediated oxidative hepatic damage via enhancement of antioxidant defense systems. The membrane stabilization and detoxification potential of Z. mays, S. maydis in APAP-mediated oxidative routs in the kidneys of Wistar rats were evaluated over a 14-day period. Nephrotoxic rats were orally pre- and post-treated with the fraction and vitamin C (reference drug). The data obtained revealed that, the APAP-mediated significant elevations in the serum concentrations of creatinine, urea, uric acid, sodium, potassium and tissue levels of oxidized glutathione, protein oxidized products, lipid peroxidized products and fragmented DNA were dose-dependently assuaged in the extract-treated animals. The extract also markedly improved creatinine clearance rate, glutathione and calcium concentrations as well as activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase in the nephrotoxic rats. These improvements may be attributed to the antioxidative and membrane stabilization activities of the extract. The observed effects compared favourably with that of vitamin C and are indicative of the ability of the extract to prevent progression of renal pathological conditions and preserve kidney function as evidently supported by the histological analysis. Although, the effects were prominently exhibited in the extract-pretreated groups, the general results from the experiment indicate that the extract could prevent or extenuate APAP-mediated oxidative renal damage via fortification of antioxidant defence mechanisms. Overall, the results from this research have enriched biochemical and pharmacological evidence supporting the ethnomedicinal use of Z. mays, S. maydis in the management of renal dysfunctions.enAcetaminophenAntioxidantBioactivationCorn silkMaizeOxidative nephropathyPharmacologyPhytotherapyRenal replacement therapyToxicologyThesis (Ph.D. (Biochemistry))--University of the Free State, 2016ThesisUniversity of the Free State