Browsing by Author "Wan Muhamad Salahudin Wan Salleh"

Chronic exposure to inorganic arsenic has been linked with multiple medical conditions, which shifted the use of inorganic to the organic-based herbicide, monosodium methyl arsenate (MSMA). However, with increasing numbers of chronic kidney disease of unknown causes (CKDu), chronic exposure to herbicide is believed to be one of the potential explanation. To date, studies on the effects of organic arsenic exposure on the kidney are limited. Therefore, this study aimed to investigate the effect of chronic oral organic arsenic exposure on the rat’s kidney. Thirty-six Sprague Dawley rats (N=36) were randomly divided into MSMA exposed, and its corresponding control groups for 2-,4- and 6-month, each with six animals per group. The exposed groups were given oral MSMA at 63.20 mg/kg body weight, while control groups received distilled water. At the end of each duration, the serum was collected for the creatinine level. The kidney tissues were harvested for arsenic level measurement, histopathological, immunohistochemistry, real-time PCR analysis and ultrastructural analysis. Genes expressions were done for kidney injury marker gene (KIM-1), oxidative stress genes (Catalase, GSR, NOS1), apoptosis genes (Tp53, Caspase-3 and Caspase-9) and inflammatory genes (Interleukin-6 and Interleukin-8). Serum creatinine was not significantly different between exposed and control groups. Tissue arsenic level was significantly higher in exposed groups as compared to that of the control group. All gene expression markers were downregulated at 2-month and upregulated at 4-month except for Catalase which remained downregulated. At 6-month, only KIM-1, GSR and Caspase-3 remained upregulated. Histological, immunohistochemistry and ultrastructural findings showed chronological changes in the glomeruli and proximal tubules with increased expressions of malondialdehyde (MDA) staining, Caspase-3 and TUNEL staining with the duration of exposure. Therefore, chronic oral exposure to low dose organic arsenic has demonstrated evidence of kidney injury in rats possibly due to oxidative stress.

Type 2 Diabetes Mellitus (T2DM) is associated with histological and histochemical changes in human skeletal muscle. The changes that occur in skeletal muscle play an important role in development in insulin resistance. However, the changes are still controversial. This is due to the variation of skeletal muscle response to the changes in T2DM. In normal human skeletal muscle, different groups of muscles in the same anatomic region display different fiber type profiles and sizes. Previous study found that T2DM affects more on skeletal muscle fibers of the lower limb than the upper limb. The objective of this study was to describe the variation of histological and histochemical changes occur among lower limb muscles (LLM); Tibialis Anterior (TA) muscle, Soleus (SOL) muscle and Gastrocnemius (GAST) muscle in T2DM subjects. Skeletal muscle tissues harvested from subjects undergone below knee amputation (BKA) surgery from each TA, SOL and GAST muscle. Tissues were stained with Hematoxylin & Eosin (H&E), Reduced Nicotinamide Adenine Dinucleotide-Tetrazolium Reductase (NADH-TR), Adenosine Triphosphatase (ATPase) and Periodic Acid Schiff (PAS) staining. Qualitative and histomorphometric analyses were carried out to determine the variation in muscle fiber morphology; fiber type distribution, fiber size diameter, oxidative capacity and intramuscular capillarization. Qualitative analysis showed histological features of vascular and neuropathic changes as evidence by atrophic fibers, angulated fiber, target fiber and fiber grouping in each muscle groups. Histomorphometric analysis of fiber type distribution showed percentage distribution of fiber type in TA muscle (T1:71%, T2:29%), SOL muscle (T1:64%, T2:36%) and GAST muscle (T1:60%, T2:40%). Two-Way ANOVA was conducted to explore the impact of muscle group and fiber type on fiber diameter. Muscle group and fiber type had significant effect on fiber diameter (p<0.05). Mean of fiber diameter were 32.83, 35.76 and 36.58 ?m; for AT muscle, SOL muscle and GAST muscle respectively and mean diameter of fiber type were 35.18 (T1F) and 35.58 (T2F). For oxidative capacity among 3 muscle groups, a Two-Way ANOVA showed there were significant effects of muscle groups and fiber type on oxidative capacity (p<0.05). Mean of oxidative capacity were 1.12, 1.07 and 1.11 O.D; for TA muscle, SOL muscle and GAST muscle respectively. Intramuscular capillaries quantification revealed no significant different among 3 muscle groups (p>0.05). Mean capillary density were 178, 221 and 214 for TA, SOL and GAST respectively. In conclusion, the present study showed there were some significant histological and histochemical variations among 3 muscle groups of lower leg in T2DM subjects.