Host: The Japanese Pharmacological Society
Name : The 97th Annual Meeting of the Japanese Pharmacological Society
Number : 97
Location : [in Japanese]
Date : December 14, 2023 - December 16, 2023
Chronic inflammatory disease leads to excessive fibrosis in the intestine. Statin drugs that inhibit the Ras and Rho pathways may be useful in fibrotic diseases. Therefore, we established an experimental animal model of colorectal fibrosis and exmamined the effect of pravastatin on intestinal fibrosis. Male C57BL/6N mice were given dextran sulfate sodium (DSS) ad libitum for 7 days, followed by a 14-day rest period. This was repeated for one cycle up to a maximum of three cycles. Body weight and fecal condition were measured nd expressed as Disease Activity Index (DAI). 14-day rest period within the third cycle (Day 49-63), pravastatin was administered orally once daily for 14 days. In the DSS drinking group (control group), DAI increased and colon length shortened. Furthermore, collagen fibers and type I collagen increased in the submucosal tissue. p-SMAD3 and Rock1/RhoA expression increased. Pravastatin treatment had no effect on DAI and colon length compared to the control group. In addition, collagen fibers and type I collagen in the submucosal tissue increased as in the control group. However, the ratio of Rock1/RhoA expression was significantly decreased compared to the control group. Repeated treatment with DSS was shown to cause fibrosis with increased type I collagen in the submucosal tissue. Pravastatin inhibited ROCK1 but it failed to inhibit fibrosis. It is hypothesized that pravastatin may have contributed to the increase in fibrosis by decreasing geranylgeranyl pyrophosphate expression and exacerbating inflammation.
