Rosiglitazone promotes pancreatic regeneration in experimental model of acute pancreatitis

Abstract

Acute pancreatitis is an inflammatory disease of the pancreas caused by release of activated digestive enzymes in the pancreas. A number of therapeutic options have been explored for acute pancreatitis, but none has been unambiguously proven to be effective. Rosiglitazone has been shown to be efficacious in acute pancreatitis; thus, the present study was planned to evaluate the effect of rosiglitazone on pancreatic regeneration. Pancreatitis was induced by l-arginine in rats which were divided into three groups: cholecystokinin (CCK-8), rosiglitazone and vehicle. Rats were sacrificed at four time points after induction of pancreatitis i.e. 24h, day 3, day 14 and day 28 for determination of biochemical parameters and histological examination. Rate of DNA synthesis, immunohistochemistry and RT-PCR were performed at day 3 and day 7. Drug administration was started 2h after last L-arginine injection and continued till the day of sacrifice. The lower levels of enzyme in rosiglitazone-treated group compared to vehicle group proved the efficacy of rosiglitazone treatment in reducing severity of acute pancreatitis. The nucleic acid content and rate of DNA synthesis were significantly higher in rosiglitazone group indicating promotion of pancreatic regeneration. The histopathological score were lower in rosiglitazone group. Rosiglitazone treatment promoted pancreatic regeneration after acute injury. Currently, only symptomatic treatment is available, regeneration of pancreatic tissue can be a future strategy in the management of acute pancreatitis. Further studies are required to support the findings of the present study.

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“…This pathology is also attenuated by PPAR ligands such as RSG and pioglitazone [312,313]. In a pancreas-specific PPAR knockout mouse model, RSG fails to inhibit acute pancreatitis, showing that TZDs mitigate pancreatic inflammation by targeting pancreatic cells and not immune cells [314].…”

Use of certain herbal preparations in broiler feeds - A review

“…Aloe vera contains phyto-(induced by L-arginine in rats). It also promoted the chemicals like saponins (5.651g/100g), flavanoids spontaneous repair and regeneration process of the (3.246g/100g), alkaloids (2.471g/100g) and phenols pancreas occurring after an acute attack [59].…”

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“…The reports of Ogata et al [51] and Kojima and Umezawa [52] of the ability of caryophylline a Vinca alkaloid in inducing differentiation of pancreatic endocrine precursor cells and of Sidhu et al [53] of Rosiglitazone to promote β -cell regeneration from stellate cells are relevant in the present context. It is also clear from the present findings that, ductal cells can serve as progenitors for islet neogenesis in response to appropriate triggering stimulation(s) generated by the stress of substantial pancreatic loss, by reverting to a plastic phenotype state similar to embryonic progenitors, as has been suggested by a working hypothesis extended by Bonner-Weir and Sharma [54].…”