Apoptotic cell death of renal tubules in experimental severe acute pancreatitis

Takase, Kozo; Takeyama, Yoshifumi; Nishikawa, Junsuke; Ueda, Takashi; Hori, Yoshiaki; Yamamoto, Masahiro; Kuroda, Yoshikazu

doi:10.1016/s0039-6060(99)70009-7

Cited by 32 publications

(16 citation statements)

References 21 publications

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“…In addition, apoptosis also occurs in extrapancreatic organs such as small intestine and lung, etc., and the extent of apoptosis is closely associated with the severity of multiple organ injury [26][27][28]. Some researchers believed that apoptosis was detrimental in SAP [29][30][31][32] while the others thought that apoptosis might provide some protective effects in SAP process [18,20,33,34]. The results of this study support the latter view.…”

Section: Discussionsupporting

confidence: 78%

“…Liu XM et al [35] believed that apoptosis of vascular endothelial cells in the lung of SAP rats might lead to the occurrence of acute lung injury. Takase K et al [31] pointed out that renal tubular epithelial cell apoptosis in SAP rats might be a harmful factor for the development of kidney failure. In the early stage of SAP, the presence of myocardial ischemia/hypoxia may induce apoptosis [36].…”

Section: Discussionmentioning

confidence: 99%

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Effects of Baicalin and Octreotide on the Serum TNF-α Level and Apoptosis in Multiple Organs of Rats with Severe Acute Pancreatitis

et al. 2009

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We investigated the effects of Baicalin and Octreotide on the levels of endotoxin and TNF-alpha in blood and the effects of apoptotic changes in multiple organs of SAP rats, and explored the underlying therapeutic mechanisms of Baicalin and Octreotide. In this study, 135 SAP rats were randomly divided into model control, Baicalin treated and Octreotide treated group (n = 45), respectively, the same number of normal rats were included in sham-operated group (n = 45). The above-mentioned groups were further subdivided into 3, 6 and 12 h subgroups, respectively (15 rats in each subgroup). At 3, 6 and 12 h after operation, the mortality rate of rats, endotoxin and TNF-alpha levels in blood as well as the pathological severity scores, expression levels of Bax protein and apoptosis indexes in multiple organs were determined. Compared to model control group (1),both drugs can relieve the pathological injuries of multiple organs and decrease significantly the levels of endotoxin and TNF-alpha in blood and the mortality rate of rats in treated groups (P < 0.05 or P < 0.01); (2) the expression of Bax protein was upregulated in pancreas, lung, intestinal mucosa (P < 0.05 or P < 0.01) but downregulated in spleen and lymph nodes (P < 0.001 and P < 0.05, respectively) in Baicalin treated group; The apoptosis indexes significantly increased in pancreas, intestinal mucosa, lymph nodes and spleen (P < 0.05 or P < 0.01). (3) the expression of Bax protein was upregulated in pancreas and lung but downregulated in spleen and lymph nodes (P < 0.05 or P < 0.01) in Octreotide treated group; The apoptosis indexes significantly increased in lymph nodes and spleen in Octreotide treated group (P < 0.05 or P < 0.01). Baicalin and Octreotide share a similar therapeutic efficacy in the treatment of SAP via a mechanism that is associated with inhibiting the levels of TNF-alpha in blood and induce apoptosis in multiple organs.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Effects of Baicalin and Octreotide on the Serum TNF-α Level and Apoptosis in Multiple Organs of Rats with Severe Acute Pancreatitis

et al. 2009

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“…In addition, PAAF collected from the same animal models induced apoptosis in vivo in rat renal tubules when administered into the peritoneal cavity of a healthy rat, and this PAAF also induced apoptosis in vitro, in a dose-and time-dependent manner, in isolated rat renal tubules and in the normal rat kidney cell line NEK52E, as well as in MDCK cells. 25 …”

Section: Kidneymentioning

confidence: 99%

Significance of apoptotic cell death in systemic complications with severe acute pancreatitis

Takeyama

2005

J Gastroenterol

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In severe acute pancreatitis, multiple organ failure in the early stage after onset, and sepsis in the late stage, due to infection of pancreatic or peripancreatic devitalized tissue, contribute to its high mortality. In analogy with sepsis, evidence has accumulated of the significance of apoptotic cell death in the systemic manifestations associated with acute pancreatitis. Since we identified apoptosis-inducing activity in pancreatitis-associated ascitic fluid in 1995, a number of investigators, including our group, have reported, through animal experiments, that apoptosis occurred in the parenchymal cells constituting organs, such as alveolar epithelial cells in the lung, renal tubular cells in the kidney, and hepatocytes in the liver, and this apoptosis was involved in organ dysfunction with severe acute pancreatitis. Moreover, through clinical and experimental investigations, apoptosis has been revealed to be involved in the mechanism of infectious complications in acute pancreatitis. Namely, apoptosis in lymphatic tissues and peripherally circulating lymphocytes is involved in the impairment of cellular immunity, and apoptosis in gut epithelial cells is implicated in bacterial translocation. These results suggest that apoptotic cell death may play a considerable role in affecting mortality and morbidity in severe acute pancreatitis. Control of apoptosis could be a potent strategy for improvement of the clinical outcome in severe acute pancreatitis.

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“…Therefore, apoptotic cell injury was evaluated by TUNEL staining, based on our previous fi nding that apoptosis occurred in hepatocytes and renal tubular cells in rat SAP, and that cellular injury caused by apoptosis is involved in the mechanism of organ dysfunction. 20,21 Labeling on the nuclei (apoptosis) was observed in the hepatocytes and the renal tubules in wild-type mouse SAP (Fig. 4a,c), whereas it was reduced in the TLR4-defi cient mouse SAP (Fig.…”

Section: He and Tunel Staining Of The Liver And Kidneymentioning

confidence: 97%

Role of Toll-Like Receptor 4 in the Pathophysiology of Severe Acute Pancreatitis in Mice

et al. 2007

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Apoptotic cell death of renal tubules in experimental severe acute pancreatitis

Cited by 32 publications

References 21 publications

Effects of Baicalin and Octreotide on the Serum TNF-α Level and Apoptosis in Multiple Organs of Rats with Severe Acute Pancreatitis

Effects of Baicalin and Octreotide on the Serum TNF-α Level and Apoptosis in Multiple Organs of Rats with Severe Acute Pancreatitis

Significance of apoptotic cell death in systemic complications with severe acute pancreatitis

Role of Toll-Like Receptor 4 in the Pathophysiology of Severe Acute Pancreatitis in Mice

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