Shihang Tang1, Zhiyin Huang1, Jingsun Jiang2, Jinhang Gao1, Chong Zhao3, Yang Tai1, Xiao Ma1, Linhao Zhang1, Yanting Ye1, Can Gan1, Wei Su1, Xintong Jia1, Rui Liu3, Hao Wu4, Chengwei Tang5. 1. Lab. of gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, China; Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China. 2. Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China. 3. Lab. of gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, China. 4. Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China. Electronic address: 594264513@qq.com. 5. Lab. of gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, China; Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China. Electronic address: shcqcdmed@163.com.
Abstract
BACKGROUND & AIMS: Splenomegaly is usually taken as a consequence of liver cirrhosis. However, as a risk factor for cirrhosis, the impacts of spleen-liver axis on the development of cirrhosis are largely unknown. This study focused on the impacts of splenomegaly on the development of cirrhosis and assessment of the effects of celecoxib, a selective COX-2 inhibitor, on the splenomegaly and cirrhotic liver. MATERIALS AND METHODS: Liver cirrhosis was induced by thioacetamide (TAA). Sixty rats were randomly divided into control, TAA-16w, TAA + celecoxib groups and normal, TAA + sham, TAA + splenectomy groups. Hepatic stellate cells (HSCs) or hepatocytes were co-cultured with splenocytes from those groups. RESULTS: Splenocytes of cirrhotic rats stimulated the HSCs activation and induced hepatocyte apoptosis via enhancing oxidative stress. The hepatic levels of NOX-4 and the in situ O2- were profoundly reduced in TAA + splenectomy group by 50.6% and 18.5% respectively, p < 0.05. Celecoxib significantly decreased the hepatic fibrotic septa induced with TAA by 50.8%, p < 0.05. Splenic lymphoid tissue proliferation and proinflammatory cytokines of the cirrhotic rats were also obviously suppressed by celecoxib, p < 0.05. Compared with the HSC or hepatocyte cell line co-cultured with the cirrhotic splenocytes, the expression of alpha-SMA, NOX-4, in situ O2- or the levels of cleaved caspase3 and NOX-4 were significantly decreased in those cell lines co-cultured with cirrhotic splenocytes treated by celecoxib, p < 0.05. CONCLUSION: Splenomegaly contributed to the development of liver cirrhosis through enhancing oxidative stress in liver. Celecoxib could effectively ameliorate liver cirrhosis via reducing inflammatory cytokines and immune cells derived from spleen and suppressing oxidative stress.
BACKGROUND & AIMS:Splenomegaly is usually taken as a consequence of liver cirrhosis. However, as a risk factor for cirrhosis, the impacts of spleen-liver axis on the development of cirrhosis are largely unknown. This study focused on the impacts of splenomegaly on the development of cirrhosis and assessment of the effects of celecoxib, a selective COX-2 inhibitor, on the splenomegaly and cirrhotic liver. MATERIALS AND METHODS:Liver cirrhosis was induced by thioacetamide (TAA). Sixty rats were randomly divided into control, TAA-16w, TAA + celecoxib groups and normal, TAA + sham, TAA + splenectomy groups. Hepatic stellate cells (HSCs) or hepatocytes were co-cultured with splenocytes from those groups. RESULTS: Splenocytes of cirrhotic rats stimulated the HSCs activation and induced hepatocyte apoptosis via enhancing oxidative stress. The hepatic levels of NOX-4 and the in situ O2- were profoundly reduced in TAA + splenectomy group by 50.6% and 18.5% respectively, p < 0.05. Celecoxib significantly decreased the hepatic fibrotic septa induced with TAA by 50.8%, p < 0.05. Splenic lymphoid tissue proliferation and proinflammatory cytokines of the cirrhotic rats were also obviously suppressed by celecoxib, p < 0.05. Compared with the HSC or hepatocyte cell line co-cultured with the cirrhotic splenocytes, the expression of alpha-SMA, NOX-4, in situ O2- or the levels of cleaved caspase3 and NOX-4 were significantly decreased in those cell lines co-cultured with cirrhotic splenocytes treated by celecoxib, p < 0.05. CONCLUSION:Splenomegaly contributed to the development of liver cirrhosis through enhancing oxidative stress in liver. Celecoxib could effectively ameliorate liver cirrhosis via reducing inflammatory cytokines and immune cells derived from spleen and suppressing oxidative stress.
Authors: Shaymaa Ramzy Senousy; Mahmoud El-Daly; Ahmed R N Ibrahim; Mohamed Montaser A Khalifa; Al-Shaimaa F Ahmed Journal: Biomedicines Date: 2022-07-06