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Doctoral Degrees (Anatomy)

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Browsing Doctoral Degrees (Anatomy) by Author "Naidu, Edwin Coleridge Stephen."

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    Effects of momordica charantia on the kidney following antiretroviral therapy in male diabetic and non-diabetic animal model.
    (2019) Offor, Ugochukwu.; Azu, Onyemaechi Okpara.; Naidu, Edwin Coleridge Stephen.
    Introduction Management of HIV/AIDS has been successful with the use of antiretroviral therapy (ART). Consequently, the introduction of highly active antiretroviral therapy (HAART) has further increased the life expectancy of people living with HIV/AIDS and this has become a standard regimen in clinical practice. However, discordant views have been reported regarding its effects on the kidney; with a dearth of literature on the impact of HAART in a diabetic comorbid state on the renal morphology and the possible role of plant-based adjuvant. This study investigated the effect of mormodica charantia (M. charantia) on the kidney following HAART regimen (triplavar) and its impact in diabetic nephropathy (DN) in streptozotocin (STZ) induced diabetic rats. Materials and Methods 78 adult male Sprague-Dawley rats were divided into non-diabetic and diabetic groups. Rat models of diabetes were successfully established by intraperitoneal injection of STZ (45 mg/kg body weight). Animals were administered an adjuvant treatment of M. charantia and HAART regimen (triplavar) according to protocols. On the 10th week, animals were euthanized with an overdose of halothane and kidney tissues were harvested and processed for light microscopy and transmission electron microscopy (TEM). Blood samples were obtained via cardiac puncture and centrifuged to collect the serums for biochemical analysis. Urine samples were collected at 3weeks interval during the 10 weeks experimental period for analysis of renal function test. Body weight and blood glucose levels (BGL) were measured once a week during the 10 weeks treatment. Results In the non-diabetic group, HAART alone treated rats showed renal dysfunction which were characterized by raised levels of blood urea nitrogen (BUN) and serum creatinine (Scr), microalbuminuria and gross electrolyte disturbances (Sodium and Potassium) as well as urea retention. Also, levels of oxidative stress (superoxide dismutase-SOD, catalase-CAT and glutathione peroxidase-GPx) were significantly decreased in these groups together with an increased levels of thiobarbituric acid reactive substances (TBARS) resulting in free radical formation via auto-oxidation. More so, the histopathological results displayed severe glomerular capillary abnormalities with inflammatory cellular infiltrations. This correlated with TEM analysis that showed swollen mitochondrial in the endothelium and thickness of the basement membrane with overexpression of extracellular matrix. Furthermore, there were upregulation of circulating neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1) and tumor necrosis factor-alpha (TNF-α) following HAART alone treatment. In the diabetic groups consistent raised levels of blood glucose which remained peaked from the 5th week of experiment were seen in the diabetic control and HAART treated group. There were increased levels of both BUN and Scr. Renal function test showed leakage of albumin, retention of renal electrolytes (sodium and potassium) and high concentration of urea in the urine of diabetic control and HAART treated group. Activities of antioxidative enzymes (SOD, CAT) and levels of GSH were markedly decreased with an increased level of Malondiadehyde (MDA). Significant (p<0.05) upregulation of the gene expression profiles (NGAL, KIM-1 and TNF- α) were also seen. Qualitative light microscopic result using hematoxylin and eosin (H and E) stains showed glomerular capillary abnormalities and tubular epithelial damage. These findings correlated with other special stains (PAS and MT) which showed high proportion of glycogen, glycoproteins as well as mild deposition of collagen fibers and hyaline substances respectively. TEM analysis displayed an abnormally increased thickness of basement membrane which reflects the existence of endothelial damage (diabetic control). By contrast, following adjuvant treatment with M. charantia, (low and high dose) these abnormalities were significantly reduced thus suggesting a protective effect of M. charantia on the kidney. Conclusion M. charantia extract administration improved blood glucose levels, maintained renal electrolytes (Sodium and Potassium), reinstated renal function (BUN and Scr) restored histoarchitectural and ultrastructural patterns and prevented DN development in an STZ-induced diabetic rat model. Keywords: HAART, Nephrotoxicity, Diabetic nephropathy, TEM, M. charantia, Sprague-Dawley rats, Histoarchiteture
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    Investigating the effects of Cinnamomum-cassia nanoparticle conjugate on the Histomorphology of the kidney in type 2 diabetic rats.
    (2019) Kouame, Koffi.; Azu, Onyemaechi Okpara.; Naidu, Edwin Coleridge Stephen.; Peter, Aniekan Imu.
    Introduction Diabetic nephropathy remains one of the biggest complications of diabetes. The incidence is increasing and more patients are experiencing progressive kidney failure due to lack of hyperefficient treatment. This study investigated the antidiabetic activity of Cinnamomum cassia silver nanoparticles (AgNPs) [(CcAgNPs)] and its effects on the kidneys of Sprague-Dawley rats induced with type 2 diabetes following administration of Streptozotozin. Materials and methods Adult healthy, pathogen-free male Sprague-Dawley rats, of a total number of 65 (N=65), weighing 250.0 ± 20 g were divided into 10 groups. Groups A-E (positive controls) consists of 30 rats, with 6 rats per group and the experimental groups F-J, consists of 35 rats, with 7 animals per group. Diabetes was induced in animals using Streptozotocin 60 mg/kg administered intraperitoneally. The animals were subjected to various treatments with Cc (100 mg/kg and 200 mg/kg) and CcAgNPs (5 mg/kg and 10 mg/kg). The treatments were administered orally using orogastric gavage and administration was carried out daily following treatment protocol for 56 days. The selected protocol for the experiment was officially approved by the Animal Ethics Committee (protocol reference number: AREC/74/016D). Cinnamomum cassia Silver Nanoparticles (CcAgNPs) was synthesized using the green option and characterized using UV (ultraviolet)–TEM (Transmission electron microscopy)-FTIR (Fourier-transform infrared spectroscopy) –XRD (X-ray powder diffraction), prior to administration. The animals were sacrificed on day 56. Blood and urine samples were collected for biochemical analysis. The kidneys were examined for histopathological changes using Hematoxylin and Eosin (H&E), periodic acid Schiff and Masson’s trichrome staining. Transmission Electron Microscope (TEM) and Stereological studies were carried out as well. Results Urinalysis showed extensive protein and albumin deposits in the urine. Ketones and nitrites levels which are markers of renal function were significantly lower (p< 0.05) in groups treated with CcAgNPs compared to negative controls. Urea and creatinine were also significantly (p < 0.05) reduced in treated groups compared to negative controls. The levels of reduced glutathione (GSH) was significantly different across all groups (p < 0.05). Serum Malondialdehyde (MDA) concentrations were significantly (p < 0.05) lower in CcAgNPs compared to controls. Liver enzymes (alanine aminotransferase) ALT was reduced significantly in groups treated with a low dose of CcAgNPs compared to negative controls. In the group treated with high dose (10 mg/kg) of CcAgNPs, (Aspartate transaminase) AST levels were significantly lower (p < 0.05), compared to the group treated with Cc (Cinnamomum cassia) and to the negative control. Stereological studies showed significantly decreased (p < 0.05) number of glomeruli and tubules in groups treated with Cc and CcAgNPs, compared to the negative control. Transmission Electron Microscope (TEM) revealed the thickness of glomerular basement membrane, in experimental groups, compared to positive controls. Histopathology of renal tissue showed severe glomerular distortion, tubular lesions with H & E and thickening of the basement membrane; pyknotic nuclei and vacuolization with PAS and MT, in the untreated negative control group. Positive controls showed regular glomeruli with normal Bowman’s capsular space, normal basement membrane and regular capillary network compared to negative controls. The degree of histopathological changes in the glomeruli and tubules appear to be dose-dependent. Conclusion Diabetes negatively alters the cytoarchitecture and biochemistry of the kidneys of Sprague-Dawley rats while Cinnamomum cassia Silver Nanoparticles have the potential to ameliorate these changes. The possible pathway involved CcAgNPs may provoke the release of insulin-like, as well as the thioredoxin (Trx), which is one of the central antioxidants that can alleviate renal injuries in diabetic nephropathy. Keywords: Cinnamomum cassia; silver nanoparticles; diabetes; histomorphology
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    Testicular morphological and biochemical perturbations in experimental animals under antiretroviral therapy and the role of Naringenin, a bioactive flavonoid.
    (2018) Adana, Misturah Yetunde.; Azu, Onyemaechi Okpara.; Naidu, Edwin Coleridge Stephen.
    Declining male fertility is one of the neglected concerns of people living with HIV/AIDS in spite of a dual outlook of a social and a health dilemma. This issue of infertility is particularly relevant as majority of affected individuals are in their reproductive years. This thesis examines the impacts of the Fixed Dose Combination (FDC) of Highly Active Antiretroviral Therapy (HAART) Tenofovir/ Emtricitabine and Efavirenz (TDF/FTC/EFV) on the male reproductive capacity. It also explores the protective potentials of a bioactive flavonoid, Naringenin in testicular perturbations. The study was motivated by two major research questions namely: (1) what are the impacts of the recently approved first line antiretroviral therapy for adults FDC, TDF/FTC/EFV on the testes? (2) What is the role of Naringenin in alleviating testicular perturbations induced by HAART? Previous studies point to the negative impacts of the older generation of FDC of HAART on the semen quality and histomorphometry of the testes following a long-term use. The study addresses both the long-term and short-term use of antiretroviral drugs as observed in pre-exposure prophylaxis (PrEP) and post exposure prophylaxis (PEP). The research assesses the impacts of the drugs on the reproductive capability as well. Findings from this study support the argument that the negative effects of the drugs were consequent upon both the short-term and long-term use. To illustrate this hypothesis, the study was conducted in two distinct phases. The first phase which lasted a total of 28 days considered the duration of PEP or PrEP. The second phase which lasted a total of ten weeks captured all the stages of spermatogenesis in rats. In this phase male Sprague Dawley rats were exposed to fertile females after the treatments. The study thus advances an understanding of the mechanism of HAART-induced testicular injury. A therapeutic dose of TDF/FTC/EFV adjusted for animal weight was aministered on a total of 48 animals randomly divided into 6 equal groups each with a different treatment as follows; Group A: Control (Distilled water); Group B: HAART (TDF/FTC/EFV), Group C: Naringenin, 40 mg/kg; Group D: Naringenin, 80 mg/kg; Group E: HAART + Naringenin, 40 mg/kg; Group F: HAART+ Naringenin, 80 mg/kg. At the end of each phase, harvested testes were subjected to histomorphometry and ultrastructural analysis. The caudal epididymis was assessed for semen parameters and sperm mitochondrial DNA (mtDNA) fragmentation. Biochemical parameters such as serum levels of reproductive hormones (Luteinizing hormone and Testosterone) and intratesticular antioxidant enzyme activities were assayed. Contrary to prior beliefs, this research reveals that the immediate effects following short-term use of HAART are far more deleterious. This finding is consequent upon the significant drop in the sperm count (p˂0.001) and sperms with normal morphology (p˂0.001) compared to (p˂0.01) in the long-term. Histomorphometric analysis also revealed a significantly shrunken seminiferous tubule following a short-term use. These outcomes were associated with an increase in the mtDNA fragmentation in group B when compared to control (p˂0.05). Naringenin reversed abnormalities in groups E and F, displaying better semen parameters in both count and motility. Serum levels of testosterone were altered in both phases. The overall effects of all these changes were observed in the pregnancy rate which reduced in group B when compared to all the other groups. This study established that HAART has deleterious effects on the testicular microanatomy and function. These effects may impact on steroidogenesis and ultimately spermatogenesis. It consequently impairs fertility while Naringenin promises to be a potential complimentary adjuvant especially in the short term therapies. Keywords: HAART, semen parameters, reproductive hormones, testicular ultrastructure, 3 beta hydroxysteroid dehydrogenase.