The impact of mangiferin from Belamcanda chinensis on experimental colitis in rats.

BACKGROUND: Inflammatory bowel disease (IBD) [including Crohn's disease (CD) and ulcerative colitis (UC)] constitutes an important clinical problem. The pathogenesis of IBD remains unclear. It is believed that immune dysfunction, inflammatory mediators and oxidative damage play crucial roles in development of IBD. The condition is clinically associated with symptoms ranging from mild to severe during relapses, depending on the affected segment of the gastrointestinal tract. Bloody diarrhea with mucus, abdominal pain, weight loss and anemia are initial symptoms of both CD and UC. Differences between diseases become more evident in time, along with the development of intestinal and extraintestinal complications. Mangiferin (1,3,6,7-tetrahydroxyxanthone-C-2-ß-D-glucoside), a natural polyphenol in plants, exerts antioxidant and anti-inflammatory effects making it an interesting option for the treatment of inflammatory pathologies associated with oxidative stress in humans, such as IBD. PURPOSE: The aim of the current study was to elucidate the impact of mangiferin on colon tissues in 2,4,6-trinitrobenzensulfonic acid (TNBS)-induced colitis in rats. METHODS: Mangiferin was obtained from Belamcanda chinensis rhizomes by a multistage process. Groups of rats were pre-treated with 10, 30 or 100 mg/kg of mangiferin, or with distilled water administered intragastrically for 16 days. An ethanol solution of TNBS or saline was given rectally on the day 15 of the experiment. The experiment was terminated on the day 17. The colon was removed, cleaned, weighed and examined macro- and microscopically. Determination of tumor necrosis factor α (TNF-α), interleukin 17 (IL-17), malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were performed spectrophotometrically in homogenates of colon tissues. RESULTS: Rats in the TNBS group developed symptoms of colitis, including: body weight loss, colon mass index increase and damage of intestinal tissues with concomitant increase in TNF-α, IL-17, MDA levels and decreased SOD activity. In non-TNBS-treated rats mangiferin did not cause any changes of studied parameters. Pre-treatment with mangiferin exerted a protective effect, reducing the intensity of damage caused by TNBS. Mangiferin at the doses of 30 and 100 mg/kg reduced the macro- and microscopic damage score and the MDA level in colon tissues. Only at the dose of 100 mg/kg, mangiferin decreased TNF-α and IL-17 concentrations, and SOD activity in colon tissues. CONCLUSION: Mangiferin attenuates inflammatory changes of colon tissues in experimental, TNBS-induced colitis in rats. Protective effect exerted by mangiferin depends primarily on its anti-inflammatory activity and secondarily on its antioxidant properties.

Effects of long-term administration of pantoprazole on bone mineral density in young male rats.

BACKGROUND: Epidemiological studies suggest that long-term administration of proton pump inhibitors (PPIs) may decrease bone mineral density (BMD) and increase the risk of osteoporotic fractures. The aim of the study was to assess the influence of pantoprazole on bone metabolism in growing rats. METHODS: The experiment was carried out on twenty-four young male Wistar rats divided into two groups receiving either pantoprazole at the dose of 3mg/kg or vehicle for 12 weeks. Femoral bone mineral density (BMD) and bone histomorphometry were assessed. Serum total calcium, inorganic phosphate and markers of bone turnover were measured. RESULTS: In pantoprazole-treated rats a decreased BMD was detected (0.2618±0.0133g/cm(2)vs. 0.2715±0.0073g/cm(2), p<0.05). Bone histomorphometry revealed a decrease in growth plate thickness (G.Pl.RTh.) (161.0±27.8µm vs. 195.0±20.8, p<0.05) in pantoprazole-treated animals. Serum total calcium level and osteocalcin concentrations were decreased in the pantoprazole-treated group (9.62±0.55mg/dl vs. 10.15±0.38mg/dl, p<0.05 and 242.7±44.4pg/ml vs. 342.5±123.3pg/ml, p<0.05, respectively). CONCLUSION: We observed that PPIs might have a negative impact on bone formation in growing rats mainly due to their inhibitory effects on the gastric proton pump, with probable deterioration of calcium absorption and decrease in growth plate thickness.

Impact of morin-5'-sulfonic acid sodium salt on cyclophosphamide-induced gastrointestinal toxicity in rats.

BACKGROUND: The aim of this study was to evaluate the effect of morin-5'-sulfonic acid sodium salt (NaMSA) on cyclophosphamide-induced gastrointestinal changes in rats. METHODS: Rats received intragastrically 0.9% saline (group C), cyclophosphamide (15 mg/kg) (group CX), NaMSA (100 mg/kg) (group M) or cyclophosphamide (15 mg/kg) with NaMSA (100 mg/kg) (group M-CX), respectively, for 10 days. RESULTS: No histological lesions were observed in the liver and the large intestine in the control group and group receiving NaMSA. In the cyclophosphamide-treated group, a generalized blurred trabecular structure, hepatocyte apoptosis, focal and diffuse necrosis were noticed in the liver and atypia of epithelial cells or adenoma were noticed in the large intestine. In the group receiving both cyclophosphamide and NaMSA, hepatocyte apoptosis in the liver was observed less frequently. Histological examination of the small intestine revealed: low-grade dysplasia adenoma in the C, M, CX and M-CX group (in 44%, 0%, 100%, and 55.6% of specimens, respectively) with adenocarcinoma in 55.6% of specimens in the cyclophosphamide-receiving group only. Adenoma with high-grade dysplasia was observed in the control and NaMSA-receiving group with a similar frequency (22%). In addition to the histological evaluation, blood cell count parameters, as well as total protein concentration, blood glucose level, amylase, ALT, AST and GGTP activities were evaluated. Cyclophosphamide impaired weight gain, decreased blood cell count parameters and total protein concentration, and increased the GGTP activity. Those changes were not reversed by NaMSA. CONCLUSIONS: Summing up, NaMSA may protect against some cyclophosphamide-induced histological abnormalities in the gastrointestinal tract, including intestinal neoplasia in rats.

The impact of morin, a natural flavonoid, on cyclophosphamide-induced changes in the oxidative stress parameters in rat livers.

BACKGROUND: Cyclophosphamide (CPX) has many adverse effects, partly due to oxidative stress induction in various tissues. Morin is one of the natural flavonoids with strong antioxidant properties. OBJECTIVES: The aim of the current research was to estimate the influence of morin on changes in antioxidant parameters in rat livers after cyclophosphamide administration. MATERIAL AND METHODS: The study was performed on Wistar rats. The rats in Group C received 0.9% saline; those in Group CX received cyclophosphamide (CPX); and those in Group M-CX received CPX with morin. Cyclophosphamide and morin were given by gastric gavage for 10 consecutive days at doses of 15 mg/kg and 100 mg/kg, respectively. Malondialdehyde (MDA) and glutathione (GSH) concentrations, superoxide dismutase (SOD) activity and catalase (CAT) activity were determined in liver tissue homogenates. RESULTS: CPX caused a significant decrease in SOD activity and GSH levels, but only the latter was fully restored by morin. There were no significant differences in CAT activity in the various groups. CPX also insignificantly decreased MDA levels, which was aggravated by co-administration of morin. CONCLUSIONS: The results obtained indicate that morin may exert some protective action on CPX-induced changes in the antioxidant state in rat livers.