AIM:To investigate the protective effects of gastric pentadecapeptide BPC 157 on acute and chronic gastric ulcers in rats and to compare the results in therapy of human gastric ulcers by different administration methods. METHODS:Gastric pentadecapeptide BPC 157 was administered (initial single or continuous administration) into rats either intragastrically or intramuscularly before (induced acute gastric ulcer) or after (induced chronic gastric ulcer) the applications of inducing agents, and each animal was sacrificed to observe the protective effects of BPC 157 on gastric ulcers. RESULTS:Both intramuscular (im) and intragastric (ig) administration of BPC 157 could apparently reduce the ulcer area and accelerate the healing of induced ulcer in different models and the effect of im administered BPC 157 was better than that of ig. The rats treated with higher dosages (400 ng/kg, 800 ng/kg) of BPC 157 (im and ig) showed significantly less lesion (P<0.01 vs excipient or saline control), the inhibition ratio of ulcer formation varied between 45.7% and 65.6%, from all measurements except 400 ng/kg BPC 157 in pylorus ligation induced model (P<0.05), in which the inhibition rate was 54.2%. When im administered (800 ng/kg BPC 157) in three models, the inhibition ratio of ulcer formation was 65.5%, 65.6% and 59.9%, respectively, which was better than that of famotidine (its inhibition rate was 60.8%, 57.2% and 34.3%, respectively). Continuous application of BPC 157 (in chronic acetate induced gastric ulcer) could accelerate rebuilding of glandular epithelium and formation of granulation tissue (P<0.05 at 200 ng/kg and P<0.01 at 400 ng/kg and 800 ng/kg vs excipient or saline control). CONCLUSION:Both im and ig administered gastric pentadecapeptide BPC 157 can apparently ameliorate acute gastric ulcer in rats and antagonize the protracted effect of acetate challenge on chronic ulcer. The effect of im administration of BPC 157 is better than that of ig, and the effective dosage of the former is lower than that of the latter.
We have investigated the protective effects of grape seed proanthocyanidins on doxorubicin-induced toxicity in tumour-bearing mice. The intraperitoneal administration of doxorubicin (2 mg kg(-1) every other day, cumulative dosage for 18 mg kg(-1)) significantly inhibited the growth of sarcoma 180, and induced myocardial oxidative stress with decreased superoxide dismutase and glutathione peroxidase activity while increasing malondialdehyde formation in the heart or serum. Doxorubicin-induced myocardial oxidative stress also reduced lactate dehydrogenase and creatine kinase activity in the heart and elevated their levels in the serum. Doxorubicin also affected immune functions of tumour-bearing mice with significantly decreased interleukin-2 (IL-2) and interferon-gamma (INF-gamma) production, and slightly decreased natural killer (NK) cell cytotoxicity, lymphocyte proliferation and CD4+/CD8+ ratio. It markedly increased the percentages of cytotoxic T cells (CD3+CD8+), helper T cells (CD3+CD4+), IL-2R+CD4+, and IL-2R+ cells as compared with untreated tumour-bearing mice. The intragastric administration of proanthocyanidin (200 mg kg(-1) daily) significantly inhibited tumour growth, and increased NK cell cytotoxicity, lymphocyte proliferation, CD4+/CD8+ ratio, IL-2 and INF-gamma production. Moreover, proanthocyanidin strongly enhanced the anti-tumour effect of doxorubicin and the above immune responses, and completely eliminated myocardial oxidative stress induced by doxorubicin. In conclusion, intragastric administration of proanthocyanidin could enhance the anti-tumour activity of doxorubicin and ameliorate doxorubicin-induced myocardial oxidative stress and immunosuppression in tumour-bearing mice.
Ulcerative colitis (UC) is characterized by oxidative and nitrosative stress and neutrophil infiltration. In the present study, we aimed to investigate the therapeutic effect of ginsenoside Rd (GRd) in rats with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced recurrent UC. After UC was twice-induced by intracolonic injection of TNBS, rats were intragastrically administered different doses of GRd per day for 7 days. The colonic lesions and inflammation were evaluated both histologically and biochemically. Compared with the TNBS group, GRd treatment facilitated recovery of pathologic changes in the colon after induction of recurrent UC, as evidenced by a significant reduction of colonic weight/length ratio and macroscopic and microscopic damage scores (p < 0.01). The myeloperoxidase and inducible nitric oxide synthase activities with malonyldialdehyde and nitric oxide levels in colonic tissues were significantly decreased in the GRd group compared with those in the TNBS group (p < 0.01). GRd treatment was associated with remarkably increased superoxide dismutase and glutathione peroxidase activities. Results showed a valuable effect of GRd against TNBS-induced recurrent UC by inhibiting neutrophil infiltration and promoting the antioxidant capacity of the damaged colonic tissue.
We have investigated the relationship between structure and antioxidative activity of piperidine nitroxides which were substituted by different groups at the 4-position. All of the tested piperidine nitroxides inhibited malondialdehyde (MDA) generation caused either spontaneously or by a hydroxyl free radical generation system (Fe 2þ -ascorbic acid) in homogenates of liver, heart and kidney of rats, and antagonized H 2 O 2 -induced haemolysis from rat erythrocytes in a concentration-dependent manner. The same rank was followed: Bis-(4-amino-2,2,6,6-tetramethyl piperidinooxyl) (4-BIS-Tempo) and 4-azido-2,2,6,6-tetramethyl piperidinooxyl (4-N 3 -Tempo) > 4-isothiocyanate-2,2,6,6-tetramethyl piperidinooxyl (4-ISO-Tempo), 4-2 0 ,4 0 -dinitrophenylhydrazone-2,2,6,6-tetramethyl piperidinooxyl (4-D-Tempo), 4-sulfonate-2,2,6,6-tetramethyl piperidinooxyl (4-S-Tempo) and 4-amino-2,2,6,6-tetramethyl piperidinooxyl (4-NH 2 -Tempo) > 4-acetate ester-2,2,6,6-tetramethyl piperidinooxyl (4-A-Tempo) and 4-benzoate-2,2,6,6-tetramethyl piperidinooxyl (4-B-Tempo). With the exception of 4-A-Tempo and 4-D-Tempo, the tested piperidine nitroxides inhibited superoxide anion ðO 2 À Þ release from neutrophils stimulated by zymosan. The concentration required for inhibiting O 2 À release was higher than that of inhibiting MDA formation and haemolysis. However, 4-amino-2,2,6,6-tetramethyl piperidine (4-NH 2 -TempH) and other 4-position substitutes, such as NaN 3 and isothiocyanate, had no effects on MDA formation, haemolysis or O 2 À release. The results indicated that nitroxides have a wide range of scavenging reactive oxygen species (ROS) actions. The nitroxide moiety was the essential group while the 4-position substitutes could influence the activity of nitroxides on scavenging ROS.
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