Browsing by Author "Khodijah Zulkiflee"

Arsenic is a well-documented carcinogenic agent and causes acute toxicity in many organs. Humans are exposed to arsenic in several ways such as contamination of organic arsenic-based pesticide in our water supply which presumably can affect our gastrointestinal system. Colon cancer is the second most common cancer in Malaysia that causes high morbidity and mortality. However, only few studies have been done to link chronic arsenic exposure to the development of colon carcinoma. This study aimed to investigate the effect of chronic low dose of organic arsenic exposure to colonic mucosa. Sixty Sprague Dawley rats were divided equally into control and treated groups. Treated group received oral gavage of 42.13 mg/kg of Monosodium Methanearsonate (MSMA) which equals to 1/30 of LD50 MSMA in rat, to mimic the concentration of organic arsenic in our drinking water. While control group received distilled water. Each group was further divided into 3 subgroups according to the duration of exposure either 2 months, 4 months or 6 months before they were euthanized for tissue harvesting. The specimens were processed for methylene blue staining of the luminal surface of the mucosa, hematoxylin and eosin staining for quantitative study, immunohistochemistry for p21 marker expression and scanning electron microscopic study for surface topography. Scanning electron microscopic study of the luminal surface in treated rats showed varying degrees of inflammatory reactions proportional to the duration of exposures. Colonic sample from 2-month treated group revealed colonic mucosal surface had less homogeneity in size and shape of individual glandular units with slit-like crypt orifice. However, it was still covered with a dense coat of microvilli. Colonic sample from 4-month treated group showed the individual glandular units had less distinct border and stellate- shaped of orifice and decreased in the number of microvilli. Colonic sample from 6-month treated group showed the most obvious findings where there was formation of prominent cleft that gave cerebriform appearance on colonic mucosal surface and the number of microvilli also was reduced. However, there was no obvious epithelial changes observed in full thickness H&E stained colonic mucosa of treated and control rats. The expression of p21 marker was also negative in treated and control samples. The means mitotic count per area micron square were significantly lower in 4 months and 6 months treated groups as compared to similar interval control groups respectively. In 4-month Control (M = 1106.81, SD = 296.74) and Treatment (M = 668.83, SD = 367.39) groups; t(14) = -2.625, p = 0.020. In 6-month Control (M = 974.18, SD = 686.42) and Treatment (M = 233.56, SD = 157.94) groups; t(9) = -2.341, p = 0.044. However, the difference of the mean mitotic count per micron square between control and treated groups after 2 months exposure was not significant (p > 0.05). In conclusion, chronic exposure to organic arsenic demonstrated temporal topographical changes to luminal surface of colonic mucosa and paradoxically reduction in intestinal epithelium proliferative rate.

Hypertensive disorders of pregnancy (HDPs) contribute to a significant percentage of maternal and foetal morbidity and mortality worldwide. Despite the normalisation of blood pressure postpartum, women with a history of HDPs have an increased two-to-four-fold risk of developing cardiovascular diseases (CVDs) later in life. One of the aetiologies of CVDs is endothelial dysfunction. We hypothesised that the transient high blood pressure during HDPs leads to persistent and ongoing endothelial dysfunction (ED) and, ultimately, the development of CVDs in women. This study aimed to explore the effects of high blood pressure during pregnancy through histopathological, biochemical, immunohistochemical (IHC), and ultrastructural studies at one month postpartum. Twenty-four female Sprague-Dawley (SD) rats were assigned to four groups (n = 6), comprising two treatment groups administered with N?-Nitro-L-Arginine Methyl Ester Hydrochloride (L-NAME) and two control groups. All rats were sacrificed on Day 30 postpartum. The mesenteric arteries (resistance arteries) were harvested and preserved for histopathological and ultrastructural studies. Blood was taken for the biochemical study of nitric oxide (NO) and endothelin-1 (ET-1), and their concentrations were determined by enzyme-linked immunosorbent assay (ELISA). The endothelin-1 A receptor (ETAR) and endothelin-1 B receptor (ETBR) expression of the resistance arteries were measured by immunohistochemical studies. During the postpartum period, the mean concentrations of ET-1 and NO were not significantly altered in all groups, and there were no significant changes in the mean immunoreactivity of the ETAR and ETBR for the tunica intima and media. For quantitative studies, the mean media-to-lumen ratio, and the endothelial cell counts per length ratio were preserved between the control and treatment groups. Although the mean nucleus-to-cytoplasmic ratio or internal elastic lamina (IEL) thickness remained unaltered between the control and treatment groups, the ultrastructural examination using a transmission electron microscope revealed remarkable ultrastructural changes in the resistance arteries that were not visible by histopathological study. The endothelial cells of the pregnant + L-NAME (PL) group exhibit irregular nuclei, discontinuous cytoplasmic boundaries, numerous abnormal vacuolization, dilatation of subendothelial space (SES), fragmented IEL, and abundant extracellular matrix (ECM) substances below IEL. In conclusion, the endothelium of the resistance arteries of hypertension-induced pregnant rats showed substantial evidence of ultrastructural changes after postpartum. Despite there being no further insult, it indicates that there is an initial pathology for ED due to high blood pressure during HDPs. This may result in the later development of CVDs in women.