Induction of apoptosis by artemisinin relieving the severity of inflammation in caerulein-induced acute pancreatitis

Abstract

AIM:To observe the apoptosis and oncosis of pancreatic acinar cells and secondary inflammatory reaction in pancreatic tissue from rats with acute pancreatitis (AP), and the influences of artemisinin on them. METHODS: AP was induced by 4 intraperitonealinjections of caerulein at 1 h intervals. To induce apoptosis, solution of artemisinin (50 mg/kg) was given intraperitoneally 1, 12, 24 and 36 h after the last caerulein injection. Histological examination of impairment of pancreatic tissue and detection of serum amylase were performed to evaluate the severity of acute pancreatitis. Apoptosis and oncosis were detected with acridine orange (AO) and ethylene dibromide (EB) staining. Caspase-3 and myeloperoxidase (MPO) activity were measured by colorimetric assay. Nuclear factor-kappa B (NF-κB) activation was detected by flow cytometry. Macrophage inflammatory protein-1α (MIP-1α) protein was measured by Western blot. Interleukin-1β (IL-1β) mRNA was detected by RT-PCR. RESULTS:Addition of artemisinin increased the number of apoptotic cells (11.7% ± 1.4% vs 6.3% ± 0.7%, P < 0.05), while reduced the number of oncotic cells (13.0% ± 2.4% vs 17.5% ± 2.2%, P < 0.05). The activity of caspase-3 speeded up (1.52 ± 0.21 vs 1.03 ± 0.08, P < 0.05), the pancreas pathological impairment was relieved (3.0 ± 0.5 vs 4.0 ± 0.5, P < 0.05) and the level of serum amylase decreased (5642 ± 721 U/dL vs 7821 ± 653 U/dL, P < 0.05). The activation of NF-κB (29% ± 4.1% vs 42% ± 5.8%), MIP-1α protein (3.7 ± 0.5 vs 5.8 ± 0.7), MPO (0.52 ± 0.06 U/g vs 0.68 ± 0.09 U/g), IL-1β mRNA (1.7 ± 0.3 vs 2.4 ± 0.4) in the apoptosis inducing group was obviously decreased (P < 0.05).

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

“…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.…”

“…One of the important cytotoxic mechanisms of oxygen free radicals, which were excessively generated in SAP, was to induce apoptosis [38][39][40]. Chen HM et al [30] found that neutrophils apoptosis were beneficial to SAP patients. In SAP, the number of apoptotic neutrophils decreased.…”

Soluble Epoxide Hydrolase Pharmacological Inhibition Ameliorates Experimental Acute Pancreatitis in Mice

“…Accordingly, we determined expression of markers of necrotic (MMP9) and apoptotic (active form of caspases 8, 9, and 3) cell death in control versus sEHI-treated mice prior and post-AP induction. In line with published reports (Frossard et al, 2003;Zhao et al, 2007), cerulein treatment led to significant increase in MMP9, caspase 3 expression, as well as caspases 8 and 9 (Fig. 5A).…”

Baicalin Protects Thymus of Rats with Severe Acute Pancreatitis

“…The substantial difference between apoptosis and necrosis depends on causing intense inflammatory reaction or not. According to some studies, when necrosis and apoptosis coexist and necrosis prevails, inducing apoptosis will result in protective effects on related organs [13,[19][20][21]. We have found that facilitating thymus apoptosis has active protecting effects on thymus by comparing the apoptotic indexes and pathological score.…”