Chemopreventive effects of resveratrol in a rat model of cerulein-induced acute pancreatitis

Abstract

In the past decades, a greater understanding of acute pancreatitis has led to improvement in mortality rates. Nevertheless, this disease continues to be a health care system problem due to its economical costs. Future strategies such as antioxidant supplementation could be very promising, regarding to beginning and progression of the disease. For this reason, this study was aimed at assessing the effect of exogenous administration of resveratrol during the induction process of acute pancreatitis caused by the cholecystokinin analog cerulein in rats. Resveratrol pretreatment reduced histological damage induced by cerulein treatment, as well as hyperamylasemia and hyperlipidemia. Altered levels of corticosterone, total antioxidant status, and glutathione peroxidase were significantly reverted to control levels by the administration of resveratrol. Lipid peroxidation was also counteracted; nevertheless, superoxide dismutase enzyme was overexpressed due to resveratrol pretreatment. Related to immune response, resveratrol pretreatment reduced pro-inflammatory cytokine IL-1β levels and increased anti-inflammatory cytokine IL-10 levels. In addition, pretreatment with resveratrol in cerulein-induced pancreatitis rats was able to reverse, at least partially, the abnormal calcium signal induced by treatment with cerulein. In conclusion, this study confirms antioxidant and immunomodulatory properties of resveratrol as chemopreventive in cerulein-induced acute pancreatitis.

The effect of quercetin on cerulein-induced acute pancreatitis

“…Pancreatic GSH depletion has been shown in the initial phase of acute pancreatitis. 8,11,37,38 However, while some reports have shown increased pancreatic GSSG in AP, 13,14,[37][38][39] others have found that pancreatic GSSG levels and the GSSG/GSH ratio remains essentially unchanged during the early course of AP. 10,12,14,39 Rau et al 12 demonstrated a significant decrease of GSH levels parallel with an increased ratio of GSSG/Total glutathione.…”

“…4,[6][7][8][9][10] Previous studies have confirmed the participation of ROS at early stages of AP, regardless of the underlying cause. [11][12][13] The characteristics of the pancreatitis induced by cerulein (a decapeptide and cholecystokinin analogue) resemble the early phase of AP in humans.…”

“…2,8,11 Glutathione is the most important non-enzymatic antioxidant molecule in cells. It exists in a reduced (GSH) and in an oxidized form (GSSG): GSH is in equilibrium in GSSG, and the GSH/GSSG ratio is a measure of the redox--status of the cells: the ratio is a reliable indicator of oxidative stress and reflects the balance between antioxidant and oxidant status in cells.…”

“…Thereafter, premature activation of pancreatic enzymes, leukocyte infiltration, and cytokine production could aggravate local pancreatic injury and produce the spread of the inflammation to the rest of the organism. 11 For this reason, histological reflections of damage occur after biochemical changes and it also takes a certain period of time for the amelioration of the damage. The administration of quercetin at different points in time, to pre-and post-treatment groups can shed light on this issue.…”

Interferences of resveratrol with fura-2-derived fluorescence in intracellular free-Ca2+ concentration determinations

“…Evidences support that resveratrol plays a pivotal role in cell physiology protection. Namely, it activates cell defense pathways or it inhibits mechanisms underlying disease, leading then to protection and cell survival in different tissues (Carrasco et al 2014;Faghihzadeh et al 2014;Jha et al 2012;Joe et al 2015;Liu et al 2014;Rouse et al 2014;Sin et al 2015;Wang et al 2014 . Fura-2 has been described as a dye with a high selectivity for Ca 2?…”