Browsing by Author "Owira, Peter Mark Oroma."

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Anti-diabetic and anti-dyslipidaemic effects of grapefruit juice.
Ngubane, Sanelisiwe Precious.; Owira, Peter Mark Oroma.
Background Hypoglycaemic effects of grapefruit juice in diabetic rats have been previously reported. The mechanisms by which grapefruit juice lowers blood glucose are not known. This study aimed to investigate the hypoglycaemic and anti-dyslipidaemic effects of grapefruit juice, as well as to elucidate the possible mechanism/s of action of this juice. Materials and Methods Male Wistar Rats (Rattusnovergicus) of 200-300 g body weight (BW) were randomly divided into five groups (n=6). Animals in group 1 were treated with 3.0 ml/kg of water for 60 days, by oral gavage. Groups 2, 4 and 5 were rendered diabetic by a single intraperitoneal injection of 60 mg/kg BW of streptozotocin. Group 5 was further treated with 4.0 U/kg of insulin (subcutaneously, twice daily), while groups 3 and 4 were orally treated with 3.0 ml/kg of GFJ. Fasting blood glucose and glucose tolerance tests were done in all the groups. Plasma insulin levels were also measured. Hepatic glycogen content, glucokinase and glucose-6-phosphatase (G6Pase) activities were measured in homogenised liver tissues. Plasma lipid levels were measured and hepatic enzymes (Acetyl-Coenzyme Aacetyl Transferase (ACAT) and 3-Hydroxy-3-Methyl-Glutaryl-CoA (HMG-CoA reductase) expression was determined. Results Diabetic rats showed significantly reduced weight gain, but higher water consumption in comparison to the controls. Fasting blood glucose was significantly higher in the diabetic group compared to controls, but were significantly (p<0.05) attenuated in GFJ-treated diabetic group, compared to the control. Diabetic rats exhibited significantly impaired glucose tolerance compared to controls, which was, however, improved in GFJ-treated groups in comparison to the diabetic non-treated group. GFJ treatment did not improve fasting plasma insulin in diabetic animals. Glucokinase activity and hepatic glycogen concentrations were significantly increased by GJF treatment, but G6Pase was alternatively suppressed by GFJ treatment. HDL-C levels were significantly increased in GFJ treated diabetic animals. Liver ACAT and HMG-CoA reductase enzyme expression were significantly suppressed in GFJ treated diabetic animals in comparison to the non-treated diabetic animals. Conclusion The findings show that GFJ has both hypoglycaemic and anti-dyslipidaemic effects. Although it not insulinotrophic, GFJ improves glucose intolerance in diabetic animals by supressing hepatic gluconeogenesis. Furthermore, GFJ improved plasma lipid profiles and supressed the liver expression of ACAT and HMG-CoA reductase enzymes.
Anti-diabetic and anti-dyslipidemic effects of Naringin.
(2015) Cobongela, Sinazo Zezethu Zongeziwe.; Owira, Peter Mark Oroma.
The incidence of diabetes is expected to dramatically increase over the next decade. Dyslipidemia is the greatest risk factor of coronary heart diseases in patients with diabetes. Antidiabetic and anti-dyslipidemic effects of naringin were investigated in type 1 diabetes. Male Sprague-Dawley rats (n = 7) were treated daily with 3.0 ml/kg body weight (BW) of water (group 1), naringin (50 mg/kg BW) (groups 2, 4 and 7, respectively), regular insulin (4 U/kg BW, subcutaneously, twice daily) (group 3 and 7), and simvastatin (20 mg/kg BW) in group 6. On treatment day 45, halothane overdose was used to sacrifice the animals and blood samples were collected via cardiac puncture for plasma insulin and lipid profile analysis. Rat livers were excised, rinsed in normal saline and stored at -80⁰C for glycogen content analysis. Group 3, 4, 5, 6 and 7 exhibited weight loss, polydipsia and hyperglycemia after injection with 60 mg/kg body weight of streptozotocin. Naringin with or without insulin significantly prevented weight loss in diabetic animals compared to non-treated diabetic animals. Insulin with/without naringin, but not naringin, significantly lowered fasting blood glucose levels in diabetic rats. Naringin with/without insulin significantly improved hepatic glycogen content compared to nontreated diabetic rats. Naringin with/without insulin significantly increased the plasma insulin levels in diabetic animals compared to non-treated diabetic animals. Plasma total cholesterol, triglycerides, very low density lipoprotein, low density lipoprotein cholesterol concentrations were significantly higher in non-treated diabetic rats compared to non-diabetic controls. High density lipoprotein cholesterol was significantly higher in non-treated diabetic rats compared to non-diabetic control. Naringin with/without insulin improved lipid profile in diabetic animals, whereas simvastatin decreased only total cholesterol and triglycerides compared to non-treated diabetic animals. Naringin with/without insulin significantly decreased coronary risk index in diabetic animals compared to non-treated diabetic animals. Atherogenic index was significantly decreased by insulin or naringin with/without insulin in diabetic rats compared to non-treated rats. Naringin is not hypoglycemic but improves coronary risk index and atherogenic index in type 1 diabetes. However, naringin with insulin showed synergistic effects. This study was conducted to investigate the effect of naringin on blood glucose regulation dyslipidemia in type 1 diabetes. The results showed that naringin is not hypoglycemic, however, it improved fasting plasma insulin and hepatic glycogen. Naringin also showed anti-dyslipidemic effects by decreasing the antherogenic lipids and increasing the high density lipoprotein cholesterol. The findings suggests that naringin can be used as a dietary supplement to ameliorate diabetic dyslipidemia.
Antidiabetic and hepatoprotective effects of moringa oleifera leaf extras in streptozotocin-induced diabetes in rats.
(2018) Muzumbukilwa, Willy Tambwe.; Owira, Peter Mark Oroma.; Nlooto, Manimbulu.
Diabetes Mellitus is one of the major causes of degenerative diseases worldwide. Long term complications of diabetes include hepatic injury characterized by cirrhosis, inflammation, apoptosis, and microvascular and macrovascular aberrations. Mechanisms by which diabetes induces liver damage include the development of lipotoxicity-induced mitochondrial dysfunction and activation of inflammatory pathways that lead to progressive liver damage. Previous studies have reported that the leading cause of death in patients with diabetes mellitus is chronic liver disease. The liver is a metabolically active organ involved in many vital life functions. It performs many activities that are critical for survival. Due to its important activities, the liver is exposed to a number of insults and is one of the body's organs most subject to injury. Despite considerable progress in modern medicine, there are very few therapeutic agents that can protect the liver from hyperglycemia-induced oxidative damage and restore normal liver functions. As a result, the search for novel therapies that would be cheaper and effective in the management of liver diseases is paramount. Moringa oleifera (MO) is a multipurpose plant traditionally used for its medicinal and nutritional properties in many countries, especially in Durban, KwaZulu-Natal/ South Africa where the material for this study has been harvested. It has been shown to possess antihyperglycemic, antioxidant and anti-inflammatory properties and could possibly prevent liver injury. This study, therefore, investigated whether MO leaf extracts could mitigate hepatotoxicity associated with diabetes mellitus. Methods Male Wistar rats (250-300 g) were divided into six groups (n=7). Group A was orally treated daily with 3.0 ml/kg body weight (BW) of distilled water; group C was similarly treated with MO (500 mg/kg/BW) daily. Groups B, D, E, and F were rendered diabetic by a single intraperitoneal injection of streptozotocin (STZ) (45 mg/kg/BW in 0.1M citrate buffer, pH4.5). Diabetes was confirmed 3 days later. Additionally, group D was treated with subcutaneous insulin (2 U/kg/BW, bid) while groups E and F were orally treated daily with MO 250 mg/kg/BW and 500 mg/kg/BW, respectively. Glucose tolerance tests (GTT) were done on day 47 of the animal treatment. After an overnight fast for 8 hours, rats in all groups were intraperitoneally dosed with a D-glucose solution (3.0 g/kg BW) in 0.9% normal saline. This solution was prepared by dissolving 45 g of D-glucose anhydrous in 60 ml distilled water (0.75 g/ml). Blood glucose concentrations were measured by tail pricking at 0, 30, 60, 90, and 120 minutes, using glucometer (OneTouch select®; Lifescan Inc., Milpitas, California, USA). On day 54 of treatment, animals were sacrificed by halothane overdose. Blood was collected by cardiac puncture in heparinized tubes then separated into plasma and stored at -80˚C for further biochemical analysis. Livers were excised, snap-frozen in liquid nitrogen and similarly stored for histological analysis. Results: Diabetic animals had significantly (p<0.05) elevated Fasting Blood Glucose (FBG) and reduced insulin levels compared to controls. Treatment with either insulin or MO significantly (p<0.05) reduced FBG compared to non-treated diabetic rats. Treatment with 500 mg/kgBW significantly reduced FBG compared to treatment with 250 mg/kgBW. Calculated Areas-Under-the Curve (AUCs) from OGTT suggested that untreated diabetic rats exhibited glucose intolerance but treatment with either insulin or MO extracts significantly (p<0.05) reversed this. Liver function tests defined by Aspartate Aminotransaminase (ASAT), Alanine Aminotransaminase (ALAT),gamma-glutamyl aminotransaminase (GGT) and albumin were significantly (p<0.05) elevated in untreated diabetic group but treatment with either insulin or MO extracts significantly (p<0.05) reversed this. Treatment with 500 mg/kgBW of MO significantly (p<0.05) reduced GGT levels compared to treatment with 250 mg/kgBW. Untreated diabetic, unlike MO-treated rats, exhibited degeneration of hepatocytes and inflammatory cells infiltration with the fragmentation of the nucleus and cell lysis, necrotic hepatocytes, hepatic vein congestion, and vesicular cytoplasm compared to normal controls. Conclusion: This study has shown that methanolic leaf extracts of MO have dose-dependent antidiabetic effects. Liver function tests (ASAT, ALAT, GGT) and albumin were significantly elevated in untreated diabetic rats than those treated with MO extracts. This may justify the hepatoprotective effects of MO extracts in streptozotocin-induced diabetic rats.
Effects of naringenin on metformin disposition in a diabetic rat model.
(2018) Mofo Mato, Edith Pascale.; Owira, Peter Mark Oroma.; Essop, M Faadiel.
Diabetes mellitus (DM) is one of the largest global health emergencies of the 21st century. It is a major cause of blindness, kidney failure, cardiovascular diseases, lower limb amputation and accounted for 10,7 % of global all-cause mortality among people aged between 20 and 79 years old. Metformin is currently the most widely prescribed anti-diabetic drug. It exists as a hydrophilic cation at physiological pH. As such, membrane transporters play a substantial role in its oral absorption, hepatic uptake, and renal elimination. Among these transporters, organic cation transporters OCT 1 (SLC22A1) and OCT 2 (SLC22A2) are known to be important determinants of the pharmacokinetics of metformin. Naringenin, which is a plant-derived compound found in citrus fruits and vegetables, has been presumed to interact with conventional drugs and influence their disposition by modification of drug-metabolizing enzymes and transporters. The aim of this study was to investigate the effects of naringenin on organic cations transporters OCT1 and OCT2 protein expression and subsequently on metformin disposition in streptozotocin- induced diabetic rats. Methods Forty-nine male Sprague Dawley rats 250–300 g body weight (BW) were randomly divided into 7 experimental groups (n = 7). They were orally treated daily with 3.0 ml/kg body weight (BW) of distilled water (group 1) or 250 mg/kg BW of metformin (groups 3, 6 and 7) or 60 mg/kg BW of naringenin (groups 2, 5 and 7) dissolved in distilled water. Groups 4, 5, 6 and 7 were given a single intraperitoneal injection of 60 mg/kg BW of streptozotocin to induce diabetes. Animal body weights and water intake were recorded daily. Fasting blood glucose (FBG) and glucose tolerance tests (GTT) were subsequently done. Urine samples were collected from rats kept in individual metabolic cages for 24 hours, to determine output, electrolytes, albumin, creatinine and metformin levels. Thereafter, the animals were sacrificed by halothane overdose and blood was collected via cardiac puncture. Liver and kidneys were excised, rinsed in normal saline, blotted dry, weighed, snap frozen in liquid nitrogen and stored at -80°c for analysis of OCT 1 and OCT 2 protein expression by Western blot. OCT 1 and OCT 2 proteins were extracted and separated by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. Then, the gel was blotted electrophoretically onto a nitrocellulose membrane which was then probed with a primary antibody and ultimately an enzyme conjugated secondary antibody and substrate to visualize the bands representing the target proteins. Results Diabetic rats treated with naringenin and metformin either alone or in combination exhibited weight gain, improved creatinine clearance and reduced polydipsia, albuminuria, serum creatinine and blood urea nitrogen compared to untreated diabetic rats. By contrast, metformin with/without naringenin did not significantly ameliorate hyperglycemia in diabetic rats. Treatment with naringenin increased hepatic uptake and renal clearance of metformin in diabetic rats compared to untreated groups. In addition, naringenin significantly increased lactate concentrations and metabolic acidosis in rats treated with metformin compared to those that were not treated with metformin. Furthermore, diabetic rats exhibited lower OCT1 and OCT2 protein expressions but naringenin treatment significantly increased hepatic OCT1 and renal OCT2 protein expressions in the presence of metformin. Conclusion Collectively, our data suggest that metformin disposition could be affected by naringenin through the upregulation of OCT1 and OCT2 protein expressions. Upregulation of OCT1 expression may be associated with metformin-induced lactic acidosis while increased renal OCT2 expression might facilitate metformin excretion and reduce the risk of lactic acid. However, increased renal excretion of metformin by naringenin may not be sufficient to avert metformin-induced lactic acidosis.
The effects of naringenin on oxidative stress parameters in cardiac muscles of diabetic rats.
(2019) Mcobothi, Nosibusiso Esethu.; Owira, Peter Mark Oroma.
Introduction: Diabetic cardiomyopathy (DCM) is defined by hypertrophy, oxidative stress, fibrosis and inflammation of the cardiac muscle. Hyperglycemia-associated oxidative stress plays an important role in the development of cardiac hypertrophy. Naringenin a citrus fruitderived flavonoid has previously been demonstrated to have antioxidant, anti-diabetic, antiinflammatory and cardioprotective properties by as yet unknown mechanisms. Aim: To investigate the effects of naringenin on oxidative stress parameters in cardiac muscles of diabetic rats. Methods: Wister rats (250-300g) were randomly divided into six groups (n=7). Groups I and IV were orally treated daily for 56 days with 3.0 ml/ kg Body Weight (BW) of distilled water and 60 mg/kg BW of naringenin in distilled water, respectively. Groups II, III, V and VI were made diabetic by a single intraperitoneal injection of 60 mg/kg BW of streptozotocin (STZ) and similarly treated with naringenin, except group VI which was treated with insulin 2.0 U/BW bid. Group V was pre-treated with naringenin for a period of one week before STZ administration. On day 57 the animals were euthanized, blood samples collected, and the hearts were excised, weighed and stored at -80ᴼC. Antioxidant activity (catalase, glutathione peroxidase and superoxide dismutase) was measured using colorimetric commercial kits. Malondialdehyde (MDA) levels were measured using the Thiobarbituric acid reactive substances assay (TBARS) while fasting plasma insulin was measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit and insulin resistance was calculated using Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and pro-inflammatory cytokine levels were measured by commercial ELISA kits. Results: Diabetic animals presented with significant (p< 0.05) weight loss, polydipsia, increased fasting blood glucose (FBG) levels and glucose intolerance (GI) compared to control. Naringenin treatment significantly increased antioxidant enzyme levels (cardiac tissue) in diabetic animals compared to the untreated diabetic groups. MDA and TNF-α levels (in cardiac tissue) were significantly increased in the untreated diabetic groups compared to the control. Cardiac mass to body weight ratio was increased in the untreated diabetic rats compared to the naringenin treated diabetic rats. Conclusion: Naringenin pre-treatment and naringenin post STZ treatment improved diabetic symptoms, antioxidant levels, heart weights and reduced inflammation suggesting its cardioprotective effects in diabetic cardiomyopathy are due to its antioxidant properties.
The effects of naringin on glucose tolerance and ketoacidosis in type 1 diabetes.
Neondo, Murunga Alfred.; Owira, Peter Mark Oroma.
The effects of naringin (4’,5,7-trihydroxy flavonone-7-rhamnoglucoside), a flavonoid isolated from the grapefruit and other citrus fruit species were investigated on diabetic ketoacidosis (DKA) in a type 1 diabetic rat model. DKA is an acute life threatening complication of diabetes mellitus. Male Sprague-Dawley rats (225-250g) were divided into 5 groups (n=7). Group 1 (control) was treated daily with 1.0 ml/kg distilled water while group 2 was treated with 50 mg/kg of naringin, via gastric gavage respectively. Diabetes was induced in groups 3, 4 and 5 by a single intraperitoneal injection of 60 mg/kg streptozotocin in 0.1 M citrate buffer and was confirmed after 48 hours. Group 3 was further treated with subcutaneous insulin (4 IU/kg) twice daily respectively. Blood samples for analysis were collected by cardiac puncture. The animals were handled humanely according to the guidelines of the Animal Ethics Committee, University of KwaZulu Natal, number 106/13/Animal. The untreated diabetic rats (group 5) showed significant (p<0.0001) hyperglycemia, polydipsia, polyuria, weight loss, impaired glucose tolerance, low fasting plasma insulin (FPI) and low glycogen levels compared to the normal control. They also showed significantly (p<0.0001) elevated acetoacetate (AcAc), β-hydroxybutyrate (3HB), total ketone body (TKB), anion gap (AG) and potassium (p<0.05) levels compared to normal control. Furthermore, significant (p<0.01) reductions blood pH, sodium, chloride and bicarbonate (p<0.0001) levels were recorded compared to the normal control. Treatment of the diabetic groups with naringin did not improve fasting blood glucose and serum electrolyte levels but significantly improved weight loss (p<0.0001), water consumption (p<0.0001), hepatic glycogen level (p<0.05), 3HB (p<0.05), AcAc (p<0.05), TKB (p<0.01), bicarbonate (p<0.01), blood pH (p<0.01) and AG (p<0.05) compared to the diabetic control group. The results in this study therefore suggest that naringin reverses ketoacidosis but does not improve glucose tolerance in a diabetes type 1 rat model.
Grape fruit juice improves glycemic index and up-regulates expression of hepatic organic cation transporter protein (OCTI) in the rat
(2009-03) Owira, Peter Mark Oroma.; Ojewole, John Akanni Oluwole.
Abstract available in PDF file.
Grapefruit juice ameliorates nephropathy in streptozotocin induced diabetes.
(2012) Hayangah, Julia Achieng'.; Owira, Peter Mark Oroma.
Background Diabetic Nephropathy (DN) is the leading cause of end stage renal disease and mortality in diabetic patients. Over the years, medicinal plants have been used to manage diabetes and its complications. Metformin, the synthetic analogue of galegine is used as first line therapy for Diabetes Mellitus (DM) but its use is contraindicated in patients with kidney dysfunction. The management of DN currently is limited to the use of anti-hypertensive agents; ACE inhibitors and angiotensin receptor blockers. Grapefruit juice (GFJ) has shown potential as an anti-diabetogenic agent because of its ability to ameliorate hyperglycaemia and dyslipidemia but its effect on fluid and electrolyte disturbance is not known. This study was designed to investigate the effect of GFJ on renal dysfunction in streptozotocin (STZ) induced male wistar rats. Materials and Methods Male wistar rats weighing between 250-300g were divided into 7 groups (n=7) and kept in cages for the treatment period of 8 weeks. Laboratory conditions of 12 hour light/dark cycle, temperature 25±20C and humidity 50-55 % were maintained throughout the study period. Non-diabetic animals group 1 (Control) were treated orally with 1.0 ml /Kg BW of distilled water, while group 2 (ND-GFJ) were treated orally with 3.0 ml /kg BW of GFJ. The diabetic groups 3, 4, 5, 6 and 7 were starved overnight in preparation for the STZ injection. Fasting blood glucose concentration was obtained via tail prick before 45 mg or 60 mg of STZ was administered via a single injection in the peritoneal cavity. STZ was prepared by dissolving it in 0.2 ml of 0.1 M Citrate buffer at pH 4.5. Groups 3, 4 and 7 received 60.0 mg/ Kg BW of STZ while group 5 and 6 received 45 mg/kg BW of STZ. Three days following STZ induction, the diabetic state was confirmed by measuring fasting blood glucose and animals with glucose concentration greater than 6 mmol/L were included in the study. Group 4 (INS- D60) and group 5 (INS- D45) were additionally treated with 4.0 U/kg BW of insulin via subcutaneous injection (S.C) twice a day while Group 6 (GFJ-D45) and group 7 (GFJ-D60) were treated orally with 3.0ml/Kg BW of GFJ. Group 3 (D-60) were similarly treated with 1.0 ml /Kg BW of distilled water. Fasting blood glucose (FBG) and glucose tolerance tests (GTT) were done on days 1 and 58 respectively in all the treatment groups. Urine was collected for a period of 24 hours on day 59 and on the last day animals were sacrificed by halothane overdose. Blood samples were obtained via cardiac puncture; kidney tissues were removed and preserved in formalin while the liver was snap frozen with liquid nitrogen and stored in a freezer (-800C) before analysis. Results Reduced plasma insulin was accompanied by decrease in body weight and an increase in FBG accompanied by polyuria, polydipsia and glucose intolerance in the non-treated diabetic animals compared to the control. Fasting blood glucose was significantly (p<0.0001) increased in the diabetic groups and treatment with GFJ or insulin lowered FBG in groups (GFJ-D45, GFJ-D60 & INS-D60) compared to the diabetic control (D60). GFJ significantly (p=0.0034) improved glucose intolerance in diabetic animals (GFJ-D60 & GFJ-D45) when compared to diabetic control groups D-60 & D-45 respectively. Hepatic glycogen content was reduced in diabetic animals (P=0.024) and treatment with GFJ significantly (P=0.00016) increased the glycogen concentration. In the non-diabetic group (GFJ-ND) treatment with GFJ significantly (P=0.0013) increased the glycogen concentration when compared to the control group. In the diabetic animals, decreased GFR was accompanied by Na+ retention accompanied by low urinary K+ and Cl- concentration. Treatment with GFJ significantly (p<0.05) increased urinary Na+ and K+ and Cl- in the diabetic group (GFJ-D60) but did not increase urinary Cl- in non-diabetic group and consequently improved GFR in the diabetic group. Renal pathology showed structural changes in the glomerulus and treatment with GFJ had some reno-protective effect. Conclusion GFJ lowered the fasting blood glucose and improved glucose tolerance in the STZ-induced diabetic rats in a comparable manner to insulin treated diabetic rats. GFJ decreased Na+ retention and increased GFR in the diabetic animals. This study suggests that GFJ could ameliorate nephropathy associated with diabetes mellitus. These results are the first to show that GFJ has renoprotective effects in STZ-Induced diabetic rats.
Metformin does not prevent glucose intolerance but improves renal function and reduces oxidative stress in type 1 diabetes.
(2016) Driver, Christine.; Owira, Peter Mark Oroma.
Type 1 diabetes (T1D) is a chronic condition caused by the complete destruction of insulin producing pancreatic β-cells. Increased oxidative stress and impaired antioxidant capacity are associated with the development of diabetic complications such as diabetic nephropathy. Metformin, a drug commonly used in the treatment of type 2 diabetes, has been suggested to have antioxidant capacity. We hypothesise that metformin, when used as an adjunct to insulin in T1D may help prevent the development of diabetic nephropathy by decreasing oxidative stress. Sprague-Dawley rats (230-250g) were divided into 5 groups, (Group A: untreated controls, B: diabetic control, C: T1D + insulin (4U/kg twice daily), D: T1D + metformin (250mg/kg via oral gavage), E: T1D + metformin + insulin). Diabetes was induced in groups B-E by intraperitoneal streptozotocin injection at a dose of 65mg/kg body weight and diabetes was confirmed 48 hours later. Glucose tolerance test, serum and urinary electrolytes (K+,Cl- ,Na+), creatinine, urea, superoxide dismutase activity, glutathione concentration and malondialdehyde concentration were analysed. Metformin alone did not improve glucose intolerance. Both the diabetic control group as well as the group treated with metformin alone experienced hyperglycemia, polydipsia, polyuria, weight loss and impaired glucose tolerance. However, when metformin was added to insulin there was a significant increase in electrolyte excretion and also greatly improved creatinine clearance when compared to the diabetic control group. Metformin with insulin further reduced superoxide dismutase activity compared to the diabetic control, increased glutathione concentration as well as reduced malondialdehyde concentrations in both plasma and renal tissue. In conclusion, metformin has positive additive effects on oxidative stress and renal function when used as an adjunct therapy to insulin for T1D.
Naringin reversal of some aspects of diabetic nephropathy in rats type 1 streptozotocin induced diabetes.
Nkomo, Fezile Sinethemba.; Owira, Peter Mark Oroma.
The role of naringin on streptozotocin-induced diabetic nephropathy was investigated. Male Wister rats (200-300 g) were divided into six groups (n=7). Group A was treated with a vehicle (0.2 ml of 0.1M citrate buffer pH4.5) by a single intraperitoneal injection (IP) and 3.0 ml/kg/BW of distilled water and group B was treated naringin (50 mg/kg/BW) daily. Groups C, D, E and F were rendered diabetic by a single IP of STZ (60 mg/kg/BW) in 0.1M citrate buffer (pH4.5). Diabetes was confirmed after 2 days (48 hours). Group C was treated with subcutaneous insulin (4 U/kg/BW) twice a day while groups D and F were treated with naringin (50 mg/kg/BW) and ramipril (20 mg/kg/BW) which is the drug that is currently used to treat diabetic nephropathy orally, daily, respectively. On day 55, 24-hours urine samples were collected and on day 56 rats were sacrificed; blood samples were collected by cardiac puncture and kidney and liver samples were excised and snap-frozen in liquid nitrogen for further analysis. Diabetic groups (C, D, E and F) showed significant (p<0.001) hyperglycemia, weight loss, polydipsia, polyuria, impaired glucose tolerance and low fasting plasma insulin compared to the controls. Treatment with naringin improved weight loss, polydipsia, fasting plasma glucose and fasting plasma insulin. Naringin decreased fasting blood glucose but did not improve glucose intolerance and it significantly (p<0.001) improved fasting plasma insulin compared to diabetic control. Furthermore, non-treated diabetic groups significantly (p<0.001) showed elevated plasma malondialdehyde (MDA) and reduced superoxide dismutase (SOD) activities compared to the controls. Naringin further reduced renal lipid peroxidation and increased SOD activities in diabetic rats. Moreover, naringin reversed electrolytes retention and also increased glomerular filtration rate in diabetic rats. Naringin therefore ameliorates some aspects of diabetic nephropathy (GFR, serum and urine electrolytes) by reversing oxidative stress associated with DN.
Naringing reverses HIV-1 protease inhibitors-associated pancreatic beta-cell dysfunction in vitro.
Nzuza, Sanelisiwe.; Owira, Peter Mark Oroma.
Introduction: Chronic exposure to HIV-1 Protease Inhibitors (PIs) has been associated with pancreatic β-cell dysfunction and impairment of insulin secretion. PIs have been suggested to induce β-cell dysfunction through increasing oxidative stress leading to impaired insulin secretion. The study investigated whether naringin, a naturally occurring antioxidant, could reverse PIs-induced β-cell dysfunction by reducing oxidative stress. Methods: The RIN-5F cells were cultured in RPM1-1640 medium, allowed to grow to 80% confluence, exposed to different concentrations of PIs [nelfinavir (1-10 μM), saqanavir (1-10 μM) and atazanavir (5-20 μM)] in the presence of 11 mM glucose for 24 hr then subjected to insulin ELISA assay to assess dose-dependent suppression of insulin of secretion by PIs. To determine glucose-induced insulin secretion, the cells were exposed to nelfinavir (10 μM), saquinavir (10 μM), atazanavir (20 μM) 24 hr with or without glibenclamide (10 μM) in the presence of varying glucose concentrations (11-25 mM) then harvested and subjected to biochemical assays for the measurement of insulin levels, lipid peroxidation, ATP generation, Glutathione levels (GSH), Superoxide dismutase (SOD) and caspase-3 and -9 activities. Cells were further exposed to naringin (0-50 μM) in the presence of 11 mM glucose for 24 hr then subjected to insulin ELISA for insulin secretion determination. To investigate the role of PIs relative to naringin on RIN-5F cells, the cells were exposed to nelfinavir (10 μM), saquinavir (10 μM) and atazanavir (20 μM) with or without naringin (10 μM) also in the presence of 11 mM for 24 hr and similarly subjected to biochemical assays. Results: Linear regression analysis showed significant decrease in insulin levels in response to nelfinavir, saqunavir and atazanavir (r2= 0.86, 0.76, 0.95, respectively) in a dose-dependent manner. PIs significantly (p < 0.05) reduced insulin secretion and ATP production, increased lipid peroxidation, SOD and caspase-3 and -9 activities and also reduced GSH in a glucosexv dependent manner. These effects were reversed by glibenclamide. Naringin (0-50 μM) caused dose-dependent increased in insulin secretion and also reduced lipid peroxidation, SOD, caspase-3 and -9 activities, increased GSH and ATP levels in cells that were exposed to PIs. Conclusion: PIs induced β-cell dysfunction and impairment of insulin secretion by increasing oxidative stress and ATP depletion. Naringin ameliorated PIs-induced impairment of β-cell dysfunction by reducing oxidative stress.
Potential hepatoprotective effects of naringenin in nucleoside reverse transcriptase inhibitor-induced oxidative stress and apoptosis in hepatocytes in vitro.
(2019) Govender, Khmera.; Owira, Peter Mark Oroma.
Abstract available in PDF.