Naznin Muhammad

Early effects of high cholesterol diet on the kidney of an animal model

BACKGROUND: Previous studies have proven that there exists a complex association between progressive kidney damage and hypercholesterolemia. Most of them focused on the impact of chronically high blood cholesterol levels on the kidney. Information on the early effects of hypercholesterolemia on the kidney is still lacking. The aim of this study is therefore to determine early effects of high cholesterol diet on the kidney in an animal model. METHODOLOGY: Ten female Sprague-Dawley rats were divided into two groups: the control group, fed with commercial rat pellet and the high cholesterol diet (HCD) group, fed with 12% cholesterol diet with 0.3% cholic acid. Biochemical analysis of the lipid profile and renal function were performed at completed 48 hours, 7 days, and 6 weeks of the experiment. The animals were sacrificed at 6 weeks and the kidneys were harvested for histological examination. RESULTS: The HCD group rats had significantly higher levels of serum total cholesterol (at 7 days and 6 weeks). The HDL-c and triglyceride levels were, however lower at 6 weeks. The mean serum creatinine level of the HCD group was increased after 48 hours and 7 days compared to control group. Histological examination of the kidney tissue of the HCD group at 6 weeks revealed segmental mesangial hypercellularity and mesangial matrix expansion of the glomeruli. CONCLUSION: The 12% cholesterol diet induced dyslipidaemia in the animal model. It resulted in acute kidney injury based on the serum creatinine at 48 hours and also 7 days. Kidney tissues examined at 6 weeks revealed changes confined to mesangial cells of the renal glomeruli.

p16 Tumor Suppressor Gene Methylation in Diffuse Large B Cell Lymphoma: A Study of 88 Cases at Two Hospitals in the East Coast of Malaysia

Introduction: p16 gene plays an important role in the normal cell cycle regulation. Methylation of p16 has been reported to be one of the epigenetic events contributing to the pathogenesis of diffuse large B-cell lymphoma (DLBCL) which occurring at varying frequency. DLBCL is an aggressive and high-grade malignancy which accounts for approximately 30% of all non-Hodgkin lymphoma cases. However, little is known regarding the epigenetic alterations of p16 gene in DLBCL cases in Malaysia. Therefore, the objective of this study was to examine the status of p16 methylation in DLBCL. Methods: A total of 88 formalin-fixed paraffin-embedded DLBCL tissues retrieved from two hospitals located in the east coast of Malaysia, namely Hospital Tengku Ampuan Afzan (HTAA) Pahang and Hospital Universiti Sains Malaysia (HUSM) Kelantan, were chosen for this study. DNA specimens were isolated and subsequently subjected to bisulfite treatment prior to methylation specific-PCR. Two pairs of primers were used to amplify methylated and unmethylated regions of p16 gene. The PCR products were then separated using agarose gel electrophoresis and visualised under UV illumination. SPSS version 12.0 was utilised to perform all statistical analysis. Result: p16 methylation was detected in 65 of 88 (74%) samples. There was a significant association between p16 methylation status and patients aged >50 years old (p=0.04). Conclusion: Our study demonstrated that methylation of p16 tumor suppressor gene in our DLBCL cases is common and significantly increased among patients aged 50 years and above. Aging is known to be an important risk factor in the development of cancers and we speculate that this might be due to the increased transformation of malignant cells in aging cell population. However, this has yet to be confirmed with further research and correlate the findings with clinicopathological parameters.

Organic Arsenical Exposure Stimulates Atherosclerosis Through Oxidative Stress Increase and Adhesion Molecule Expression

Approximately 100 million people are exposed to arsenic worldwide, majorly through drinking water and anthropogenic activities. Monosodium methylarsonate (MSMA) is a potent organoarsenical content of herbicides used in many Asian countries. Epidemiological studies have linked inorganic arsenic exposure with atherosclerosis, whereas organoarsenicals toxicological studies are scanty. Paraoxonase 1 (PON1) enzyme suppresses systemic Ox-LDL generation, thereby preventing atherosclerosis. We investigated effects of MSMA oral exposure on PON1, lipid peroxidation and atherosclerosis development. Five groups (n=11) of Sprague- Dawley rats received daily intubation of MSMA at 0 (control), 42.1, 63.2, 126.4 and 210.7 mg/kg BW respectively for 16 weeks. Serum samples were analysed for PON1 activities, Ox-LDL and MDA levels. Histomorphometric evaluation (H&E and VVG) and immunohistochemistry (VCAM-1 and ICAM-1) were done on aorta. High mortality rate led to discontinuation of 126.4 and 210.7 mg/kg BW treatment groups. Groups treated with 42.1 and 63.2 mg/kg B.W. MSMA had a significantly higher MDA (p=0.004,CI: 2.73-0.82) and Ox-LDL (p<0.0001,CI: 2425.07-955.45) levels but lower PON1:Ox-LDLratio (p<0.0001,CI: 0.49-1.07) compared to control. Microscopically, treatment groups showed early atherosclerotic intima thickening and positive VCAM-1 and ICAM-1 expressions. In conclusion, chronic MSMA exposure reduced PON1 ability to hydrolyse Ox-LDL and also induced inflammation by elevating oxidative stress that supports early atherosclerosis development.