Solomon Rotimi

Erythrocyte acetylcholinesterase activity as a surrogate indicator of lead-induced neurotoxicity in occupational lead exposure in Abeokuta, Nigeria

Dose-effect and dose-response relationships in occupational neurotoxicology are rarely studied by means of biochemical methods. In order to investigate the potential neurotoxic effects of lead during occupational exposure to this metal, the activity of erythrocyte acetylcholinesterase (AcChE), as well as blood pressure and pulse, were determined in various artisans in Abeokuta, Nigeria, who have been shown to be occupationally exposed to lead, and these were related to blood lead levels. AcChE activity in the artisans was inhibited to varying extents. While AcChE activity was inhibited to the tune of 39% in the male petrol station attendants, the inhibition amounted to 32% in female petrol station attendants. In other artisans, AcChE inhibition ranged from 31% in the welders to 38% in painters. The lowest inhibition of 15% was obtained in the panel beaters. Correlations, as calculated by Pearsons method, revealed a significant (p<0.001) inverse linear relationship between AcChE activity and blood lead levels (r=-0.40; y=-120.38x+13935.59; p<0.001). Blood pressure and pulse were not significantly different between control and lead-exposed subjects. Our findings suggest that erythrocyte AcChE activity could be used as a biomarker of lead-induced neurotoxicity in occupationally exposed subjects.

Persistence of acidosis in alloxan-induced diabetic rats treated with the juice of Asystasia gangetica leaves

Background: Diabetes mellitus is gradually becoming a global health burden leading to an increase in the search for herbal hypoglycemic agents as alternatives to synthetic ones. Asystasia gangetica is one of the herbs used in folklore system of medicine for managing hypoglycaemia associated with diabetes. Materials and Methods: The influence of the juice of A. gangetica leaf on alloxan-induced diabetic rats was assessed by treating diabetic rats with 25%, 50% and 75% fresh juice and glibenclamide for 5 weeks. Afterwards, the plasma concentrations of glucose, triacylglycerols, total cholesterol, high-density lipoprotein (HDL) cholesterol, thiobarbituric acid reactive substances and bicarbonate were assayed spectrophotometrically. Results: Treatment of the diabetic rats with the juice significantly (P < 0.05) reduced the elevated plasma levels of glucose to a level not significantly (P > 0.05) different from that of glibenclamide. The juice also significantly (P < 0.05) reduced the plasma lipid peroxidation and improved the lipid profile, as indicated by a significant (P < 0.05) reduction in the total cholesterol: HDL cholesterol ratio. However, there was a significant (P < 0.05) rise in the level of bicarbonate as result of the juice treatment from 28.15 ± 2.82 mmol/l in normal control to 60.83 ± 17.46 mmol/l in diabetic control and to 122.20 ± 34.68 mmol/l, 120.95 ± 35.09 mmol/l and 115.85 ± 11.79 mmol/l in 25%, 50% and 75% juice, respectively. Conclusion: Therefore, this inability of A. gangetica to prevent acidosis detracts from the potential of its usefulness in managing diabetes.

Inability of Legumes to Reverse Diabetic-Induced Nephropathy in Rats Despite Improvement in Blood Glucose and Antioxidant Status

Diabetes mellitus has assumed epidemic proportions in most parts of the world, including developing countries, with vascular and renal complications being the major causes of death. Evidence is emerging that legumes play a beneficial role in diabetes and its associated complications. In connection with the above, four groups of alloxan-induced diabetic rats were fed on four different legume-based (Vigna unguiculata ssp. dekindtiana var. dekindtiana, V. unguiculata ssp. unguiculata, Sphenostylis stenocarpa, and Vigna subterranean) diets. Feeding rats with these diets for 5 weeks resulted in reduction of plasma glucose and changes in biomarkers of oxidative stress-namely, superoxide dismutase (SOD), peroxidase (PER), and thiobarbituric acid-reactive substances (TBARS). None of the legumes reversed the increase in plasma total protein associated with diabetes. The legumes increased PER activity and decreased the level of TBARS in the erythrocytes. A decrease in the activities of PER and SOD was observed in the kidneys of the diabetic rats. Nitric oxide (NO) production in the erythrocytes of the diabetic rats (as an index of diabetic endothelial dysfunction) increased for all the legumes in the following order: V. unguiculata ssp. unguiculata, V. unguiculata ssp. dekindtiana var. dekindtiana, V. subterranean, and S. stenocarpa. There was a significant increase (P < .05) in the uric acid concentration in the kidneys of treated rats. It is concluded that while the legumes have beneficial effects on reduction of hyperglycemia and strengthening the antioxidant status of the diabetic animals, the increased kidney uric acid concentration should be of concern.

Computational and experimental analysis identified 6-diazo-5-oxonorleucine as a potential agent for treating infection by Plasmodium falciparum

Plasmodium falciparum (PF) is the most severe malaria parasite. It is developing resistance quickly to existing drugs making it indispensable to discover new drugs. Effective drugs have been discovered targeting metabolic enzymes of the parasite. In order to predict new drug targets, computational methods can be used employing database information of metabolism. Using this data, we performed recently a computational network analysis of metabolism of PF. We analyzed the topology of the network to find reactions which are sensitive against perturbations, i.e., when a single enzyme is blocked by drugs. We now used a refined network comprising also the host enzymes which led to a refined set of the five targets glutamyl-tRNA (gln) amidotransferase, hydroxyethylthiazole kinase, deoxyribose-phophate aldolase, pseudouridylate synthase, and deoxyhypusine synthase. It was shown elsewhere that glutamyl-tRNA (gln) amidotransferase of other microorganisms can be inhibited by 6-diazo-5-oxonorleucine. Performing a half maximal inhibitory concentration (IC50) assay, we showed, that 6-diazo-5-oxonorleucine is also severely affecting viability of PF in blood plasma of the human host. We confirmed this by an in vivo study observing Plasmodium berghei infected mice.

Tissue dyslipidemia in salmonella-infected rats treated with amoxillin and pefloxacin

BackgroundThis study investigated the effects of salmonella infection and its chemotherapy on lipid metabolism in tissues of rats infected orally with Salmonella typhimurium and treated intraperitoneally with pefloxacin and amoxillin.MethodsAnimals were infected with Salmonella enterica serovar Typhimurium strain TA 98. After salmonellosis was confirmed, they were divided into 7 groups of 5 animals each. While one group served as infected control group, three groups were treated with amoxillin (7.14 mg/kg body weight, 8 hourly) and the remaining three groups with pefloxacin (5.71mg/kg body weight, 12 hourly) for 5 and 10 days respectively. Uninfected control animals received 0.1ml of vehicle. Rats were sacrificed 24h after 5 and 10 days of antibiotic treatment and 5 days after discontinuation of antibiotic treatment. Their corresponding controls were also sacrificed at the same time point. Blood and tissue lipids were then evaluated.ResultsSalmonella infection resulted in dyslipidemia characterised by increased concentrations of free fatty acids (FFA) in plasma and erythrocyte, as well as enhanced cholesterogenesis, hypertriglyceridemia and phospholipidosis in plasma, low density lipoprotein-very low density lipoprotein (LDL-VLDL), erythrocytes, erythrocyte ghost and the organs. The antibiotics reversed the dyslipidemia but not totally. A significant correlation was observed between fecal bacterial load and plasma cholesterol (r=0.456, p<0.01), plasma triacyglycerols (r=0.485, p<0.01), plasma phospholipid (r=0.414, p<0.05), plasma free fatty acids (r=0.485, p<0.01), liver phospholipid (r=0.459, p<0.01) and brain phospholipid (r=0.343, p<0.05).ConclusionThe findings of this study suggest that salmonella infection in rats and its therapy with pefloxacin and amoxillin perturb lipid metabolism and this perturbation is characterised by cholesterogenesis.

Amoxillin- and pefloxacin-induced cholesterogenesis and phospholipidosis in rat tissues

BackgroundTo investigate whether amoxillin and pefloxacin perturb lipid metabolism.MethodsRats were treated with therapeutic doses of each antibiotic for 5 and 10 days respectively. Twenty four hours after the last antibiotic treatment and 5 days after antibiotic withdrawal, blood and other tissues (liver, kidney, brain, heart and spleen) were removed from the animals after an overnight fast and analysed for their lipid contents.ResultsBoth antibiotics produced various degrees of compartment-specific dyslipidemia in the animals. While plasma and erythrocyte dyslipidemia was characterised by up-regulation of the concentrations of the major lipids (cholesterol, triglycerides, phospholipids and free fatty acids), hepatic and renal dyslipidemia was characterised by cholesterogenesis and phospholipidosis. Splenic dyslipidemia was characterised by cholesterogenesis and decreased phospholipid levels. Cardiac and brain cholesterol contents were not affected by the antibiotics. A transient phospholipidosis was observed in the brain whereas cardiac phospholipids decreased significantly. Lipoprotein abnormalities were reflected as down-regulation of HDL cholesterol. Furthermore, the two antibiotics increased the activity of hepatic HMG-CoA reductase. Although erythrocyte phospholipidosis was resolved 5 days after withdrawing the antibiotics, dyslipidemia observed in other compartments was still not reversible.ConclusionOur findings suggest that induction of cholesterogenesis and phospholipidosis might represent additional adverse effects of amoxillin and pefloxacin.

Antioxidant Activity of Solenostemon monostachyus(P. Beauv.) Briq. in Induced Rats

Solenostemon monostachyus (P.Beauv.) Briq.(SE) is the object of our investigation test the mechanism of its anti-oxidative action to further establish its anti-sickling properties.. Sample: To correlate hematological parameters and antioxidant activities with the presence induced hemolytic anemia in female rats to validate other screening parameters. Place and Duration of Study: The study as carried out in the covenant university animal house and biochemistry laboratory, department of biological sciences, covenant university. sample: the animals were obtained from the Institute for advanced medical research and training (IMRAT), college of medicine, UCH, Orita-mefa, Ibadan, Oyo state and allowed to acclimatize under a 12-hour light/dark cycle for 3 weeks prior to the commencement of the study between January 2015 and February 2015. Methodology: 2-Butoxyethanol was used to induce hemolytic anemia resembling that of sickle cell disease. The methanolic extract of the leaves was orally administered for 5 days at 150 mg/kg, 200 mg/kg and 250 mg/kg of body weight doses to determine the antioxidant activities and some hematological indices of plasma in the kidney, spleen and liver of 2-butoxyethanol hemolyticinduced rats. Sample: we used 49 Wistar albino rats (49 female; weight: 95-120 g). Hematological examination (PCV, MCV, RBCs, and hemoglobin [Hb] count) and sICAM levels was done besides antioxidant activities (bilirubin, glutathione, superoxide dismutase, TBARS and peroxidase). Weight of the animals was also calculated. Results: The results were analyzed using ANOVA. The result of the oxidative stress markers showed that SOD, TBARS and peroxidase were insignificant (P>0.05) in the kidney, liver and spleen of all the rats while GSH in the kidney and liver insignificantly high in the SM-treated rats while GSH in the spleen was significantly increased in SM-150 (7.67±2.19) compared to control. Conclusion: These doses have shown that they can be used alongside other drugs to alleviate oxidative stress in hemolytic anemic related diseases such as sickle cell disease. These predictors, however, need further work to validate reliability.

Modeling of the Glycolysis Pathway in Plasmodium falciparum using Petri Nets

Malaria is one of the deadly diseases, which affects a large number of the worlds population. The Plasmodium falciparum parasite during erythrocyte stages produces its energy mainly through anaerobic glycolysis, with pyruvate being converted into lactate. The glycolysis metabolism in P. falciparum is one of the important metabolic pathways of the parasite because the parasite is entirely dependent on it for energy. Also, several glycolytic enzymes have been proposed as drug targets. Petri nets (PNs) have been recognized as one of the important models for representing biological pathways. In this work, we built a qualitative PN model for the glycolysis pathway in P. falciparum and analyzed the model for its structural and quantitative properties using PN theory. From PlasmoCyc files, a total of 11 reactions were extracted; 6 of these were reversible and 5 were irreversible. These reactions were catalyzed by a total number of 13 enzymes. We extracted some of the essential reactions in the pathway using PN model, which are the possible drug targets without which the pathway cannot function. This model also helps to improve the understanding of the biological processes within this pathway.

Abstract B047: Biochemical parameters of prostate cancer patients in Nigeria

The screening of biochemical parameters of cancer patients and their development into reliable and specific diagnostic and prognostic biomarkers has been reported in several studies. The biochemical signature of prostate cancer patients in Nigeria may vary from others and can serve as important leads in discovery of new biomarkers for the disease. This will ultimately provide more information on the specific causes and prognosis of the disease as well as improve its diagnosis and management. This study examined some biochemical parameters including alanine transaminase (ALT), alkaline phosphatase (ALP), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TRIG), reduced glutathione (GSH), lipid peroxidation and peroxidase (POD) in the plasma of prostate cancer patients and controls. The data obtained indicate that there were no significant differences in the ALT, LDL, HDL, and POD while ALP and TRIG were significantly increased. Also, there was a significant reduction in GSH. This indicates the possible implication of ALP, TRIG, and GSH in prostate cancer disease in Nigeria and their potential to be further developed into diagnostic and prognostic biomarkers. Citation Format: Emeka Iweala, Solomon Rotimi, Faith Kanu, Chidiebere Ogo. Biochemical parameters of prostate cancer patients in Nigeria [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B047.

An Evaluation of Lipid Profile and Antioxidant Activities of Carica Papaya Seed Oil in the Heart and Liver of Female Wistar Rats.

Increasing attention is been given to Carica papaya seed due to its oil rich nature, and its medicinal value. Four feed diets consisting of 3, 5, 7, and 10 % of the oil were composed and examined for its in-vivo effect on lipid and antioxidants status of female wistar rats compared to those fed with 5 % groundnut oil based diet. The feeds were fed into the rats for 32 days, and examined for their lipid profile and antioxidant status in the liver and heart. Free fatty acids were significantly reduced (P<0.05) by 3-10 % diets in the liver, and by 10 % diet in the heart. HMG-CoA/Mevalonate ratio in the liver was significant increased (P<0.05) by the 7-10 % diets. All diets significantly increased (P<0.05) superoxide dismutase, peroxidase, and reduced glutathione in liver. Lipid peroxidation in the heart was significantly increased (P<0.05) by the 3-7 % diets. Lipid peroxidation, and phospholipid in heart were significantly reduced, and increased (P<0.05) respectively by 10 % diets. The biochemical status of rats fed with the Carica papaya seed oil based diets generally remained comparable to those fed with the groundnut oil diet in the two organs. The Carica papaya seed oil exhibited better antioxidant activities, and health benefits than the commonly consumed groundnut oil. Key words: - Carica papaya; Seeds; Oil, Quality; Antioxidants; Lipids.