The effect of Rho kinase inhibitor Y-27632 on endotoxemia-induced intestinal apoptosis in infant rats

Abstract

The aim of this study was to evaluate the effect of Rho kinase inhibitor, Y-27632 on the intestinal apoptosis in endotoxemic infant rats. Wistar albino 15-17-day-old rat pups (n = 21) were randomized to three experimental groups: (1) controls; (2) endotoxemia (LPS); and (3) endotoxemia treated with Y-27632 (LPS + Y-27632). Endotoxemia was induced in rats by intraperitoneal (i.p) injection of lipopolysaccharide (Escherichia coli serotype 0111:B4; 10 mg/kg). Y-27632 was administered 5 mg/kg i.p at three times, just, 8 and 16 h after LPS injection. Twenty-four hours after LPS injection, intestinal apoptosis was assessed by hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and immunohistochemistry for active caspase-3. Endotoxemia induced extensive apoptotic injury in the intestinal tissues. The administration of Y-27632 to endotoxemic infant rats caused a marked decrease in the number of apoptotic cells in both intestinal epithelium and lamina propria. In conclusion, the inhibition of Rho kinase with Y-27632 diminished the intestinal apoptotic damage induced by endotoxemia in infant rats.

ROCKing the Field of Intestinal Fibrosis or Between a ROCK and a Hard Place?

“…Interestingly, interleukin-6 serum levels were unchanged and one could wonder if this provides an additional clue toward a mechanism of action locally in the intestine. This finding is in discordance with other disease models in which ROCK inhibition by a different compound (Y27632) led to reduction in inflammation, [12][13][14] which may be explained by lack of specificity of Y27632 at high concentrations. It remains a challenge in inflammatory bowel disease studies to separate inflammation from fibrosis when using human specimens.…”

Rho‐kinase inhibitor Y‐27632 facilitates the proliferation, migration and pluripotency of human periodontal ligament stem cells

“…Accumulating evidence suggests that the Rho GTPases and downstream effectors such as Rho kinases regulate cell proliferation, adhesion, migration and apoptosis by affecting cell shape, cytoskeletal dynamics and cell‐cell contacts . Moreover, the Rho‐kinase inhibitor appears to enhance the survival of stem cells from a variety of sources, thereby improve the yield of differentiated cells , and inhibit the apoptosis of stem cells‐derived neuronal progenitors following animal transplantation .…”

α-Lipoic Acid Vaginal Administration Contrasts Inflammation and Preterm Delivery in Rats

“…The H-score evaluation was performed by at least 2 independent experienced histologists, blinded to the source of the samples taken from different random fields of the same sections, and the average score was utilized. 38 –42…”

“…The H-score evaluation was performed by at least 2 independent experienced histologists, blinded to the source of the samples taken from different random fields of the same sections, and the average score was utilized. [38][39][40][41][42] Expression of Cytokine Messenger RNA in Tissues RNA from paraffin-embedded tissue was extracted with the FFPE RNeasy mini kit (Qiagen, Milano, Italy) according to the indication of the producer; 1 mg of total RNA was used for complementary DNA (cDNA) synthesis, and 1 mg of total cDNA was used for each real-time reaction; analyses were performed in triplicate for each sample as described previously. 43 Total cDNA levels were standardized by normalizing them to the b-actin control and presented as the fold increase (ratio of the experimental gene value/b À actin gene value) over the control sample.…”