Carvedilol safeguards against aspirin-induced gastric damage in rats.

This study investigated the effect of carvedilol on aspirin-induced gastric damage. Male Wistar rats were divided into three groups. Control rats received the vehicle, while the aspirin group received aspirin (200 mg/kg) orally for 4 days. Rats of aspirin + carvedilol group were administered aspirin along with carvedilol (5 mg/kg; intraperitoneal) for 4 days. Animals were euthanized at the end of the treatment period, and gastric tissues were collected to perform histopathological and mechanistic studies. The results revealed that aspirin administration induced gastric ulcer as there were remarkable histopathological lesions in the form of marked necrosis, inflammation, hemorrhage, edema, and dysplastic changes. Lipid peroxidative markers such as malondialdehyde, 4-hydroxynonenal, and protein carbonyl were significantly elevated in the aspirin group. This was concurrent with a significant amelioration of antioxidants such as reduced glutathione, superoxide dismutase, and catalase. Furthermore, aspirin increased the immunoexpression of cyclooxygenase (COX) 2 and nuclear factor kappa-B (NF-κB). Aspirin induced elevation in the inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1ß. Aspirin enhanced the immunoexpression of inducible nitric oxide synthetase (iNOS) and increased the level of nitrite/nitrate in gastric tissue. On the other hand, carvedilol treatment reversed all these pathological changes. Carvedilol succeeded to enhance antioxidants in gastric tissue, attenuated lipid peroxidative parameters, and suppressed the release of inflammatory mediators. It attenuated the immunoexpression of COX-2, NF-κB, and iNOS. Collectively, carvedilol has a gastro-protective effect that could be attributed to its antioxidative and anti-inflammatory properties, which modulate NF-κB/COX-2/iNOS pathways.

Apoptosis and cell-cycle regulatory proteins in colorectal carcinoma: relationship to tumour stage and patient survival.

The quantitative assessment of apoptotic index (AI) and mitotic index (MI) and the immunoreactivity of p53, bcl-2, p21, and mdm2 were examined in tumour and adjacent normal tissue samples from 30 patients with colonic and 22 with rectal adenocarcinoma. Individual features and combined profiles were correlated with clinicopathological parameters and patient survival data to assess their prognostic value. Increased AI was significantly associated with increased bcl-2 expression (p<0.008) and the immunoprofiles that included bcl-2, but not with MI, p53, p21 or mdm2. AI was significantly associated with increased Dukes' stage from A, B to C (p<0.02) but not D, while MI showed a significant association with all Dukes' stages (p<0.05). No significant association was found between either AI or MI and prognosis. p53, p21, mdm2, and bcl-2 positivity were detected in 65.4%, 53.8%, 65.4%, and 34.6% of cases, respectively. mdm2 was significantly associated with p53 (p<0.03) and p21 (p<0.04) expression and p53 immunoreactivity was more prevalent in rectal tumours (p<0.008). In univariate survival analysis, bcl-2 overexpression was associated with more favourable patient survival (p<0.03). Positive combined patterns p53+/p21+/bcl-2+ and p21+/mdm2+/bcl-2+ (p<0.005); p53+/bcl-2+, p21+/bcl-2+, and mdm2+/bcl-2+ (p<0.01); and p53+/p21+ (p<0.02) were also associated with favourable clinical outcome. In multivariate Cox survival analysis, bcl-2 (p<0.016) and Dukes' stage (p<0.0001) were the only significant independent prognostic indicators. In conclusion, bcl-2 immunoreactivity was associated with apoptosis and could be used in combination with Dukes' stage as a means of predicting prognosis in colorectal cancer.