Genistein attenuated oxidative stress, inflammation, and apoptosis in L-arginine induced acute pancreatitis in mice.

AIM: Acute pancreatitis is a common and potentially serious condition. However, a specific treatment for this condition is still lacking. Genistein, with its anti-oxidant and anti-inflammatory effects, could possibly be used to tackle the underlying pathophysiology of acute pancreatitis. Therefore, the aim of this study was to investigate the effects of genistein on oxidative stress, inflammation, and apoptosis in acute pancreatitis induced by L-arginine in mice. METHODS: Twenty-four male ICR mice were equally divided into 4 groups: Control (Con); Acute pancreatitis (AP) group: Two doses of i.p. 350 mg/100 g body weight (BW) of L-arginine were administered 1 h apart; AP and low-dose genistein (LG) group: mice were given i.p. injection of 10 mg/kg genistein 2 h prior to L-arginine injection followed by once-daily dosing for 3 days; and AP and high-dose genistein (HG) group: mice were given 100 mg/kg genistein with the similar protocol as the LG group. Pancreatic tissue was evaluated for histopathological changes and acinar cell apoptosis, malondialdehyde (MDA) levels, immunohistochemical staining for myeloperoxidase (MPO), nuclear factor-kappa beta (NF-kB), and 4-hydroxynonenal (4-HNE). Serum levels of amylase (AMY), c-reactive protein (CRP), and interleukin (IL)-6 were measured. RESULTS: Significant increases in the degree of acinar cell apoptosis, pancreatic MDA, serum IL-6 and amylase, MPO, NF-kB and 4-HNE positivity were observed in the AP group. All these parameters declined after low- and high-dose genistein treatment. Severe pancreatic inflammation, edema, and acinar cell necrosis were observed in the AP group. Significant improvement of histopathological changes was seen in both low- and high-dose genistein groups. There were no significant differences in any parameters between low and high doses of genistein. CONCLUSION: Genistein could attenuate the severity of histopathological changes in acute pancreatitis through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

Genistein and exercise treatment reduced NASH related HDAC3, IL-13 and MMP-12 expressions in ovariectomized rats fed with high fat high fructose diet.

BACKGROUND AND AIM: Genistein (GEN) and exercise (Ex) may be regarded as an alternative treatment for non-alcoholic steatohepatitis (NASH). However, the mechanisms behind their therapeutic effects in NASH are not well-understood. EXPERIMENTAL PROCEDURE: This study investigated the roles of histone deacetylase (HDAC)3 and interleukin-(IL-)13 in the NASH model of ovariectomized (OVX) rats fed with high fat high fructose (HFHF) diet. RESULTS AND CONCLUSION: Nine weeks after being fed with HFHF diet, severe NASH pathology with mild fibrosis were seen along with an increase in HDAC3, IL-13 and matrix metalloelastase (MMP-12) expressions in OVX rats. Five weeks of either GEN or Ex treatments abrogated the increase in both HDAC3 and IL-13 expressions in OVX rats fed with HFHF diet and ameliorated NASH features, liver fibrosis and MMP-12 expression. The combination of Gen and Ex, however, did not provide additional benefits on NASH features in OVX rats fed with HFHF diet. These results suggested that GEN and Ex treatments improved HFHF diet induced NASH in OVX rats through the suppression of HDAC3, IL-13 and MMP-12 expression.

Effects of curcumin on oxidative stress, inflammation and apoptosis in L-arginine induced acute pancreatitis in mice.

BACKGROUND AND PURPOSE: Curcumin, an active constituent of rhizomes of Curcuma longa Linn, exhibits a variety of biological activities such as anti-inflammation and anti-oxidant. The present study aims to examine the effects of curcumin on oxidative stress, inflammation and apoptosis in L-arginine induced acute pancreatitis (AP) in mice. METHODS: Male ICR mice were randomly divided into 4 groups. Control group received intraperitoneal injection (i.p.) of 1% DMSO as a vehicle. AP group received two doses of i.p. L-arginine (L-Arg) 450 mg/100 g body weight (BW) at 1-hour interval. AP plus low-dose curcumin group received i.p. curcumin 50 mg/kg BW 1 hour before L-Arg injection and then once daily for 3 days. AP plus high-dose curcumin group received i.p. curcumin 200 mg/kg BW 1 hour before L-Arg injection and then once daily for 3 days. All mice were sacrificed at 72 hours. Pancreatic tissue was obtained for histological evaluation, immunohistochemical studies for nuclear factor-kappa beta (NF-kß), apoptosis and myeloperoxidase (MPO), and Western blot analyses for 4-Hydroxynonenal (4-HNE). Blood samples were collected for amylase analysis. RESULTS: Mean body weight was significantly lower in AP group than in control group, while in curcumin group, body weight was maintained. The serum amylase, number of MPO positive cells, NF-kB positive cells, TUNEL positive cells, and 4-HNE expression significantly increased in AP group when compared with control group, but decreased in low and high-dose curcumin groups. Mice in AP group developed severe pancreatic inflammation, edema and fat necrosis. While mice in low and high-dose curcumin groups showed a significant improvement in histopathological scores. There was no significant difference between low and high doses of curcumin. CONCLUSION: Curcumin could attenuate acute pancreatitis via anti-oxidant, anti-inflammation and anti-apoptosis property leading to the improvement in pancreatic damage.