1Department of Gastroenterology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China
2The Third Hospital, Beijing Medical University, Beijing 100083, China
Dr. ZHU Bing-Xi, male, born on 1965-06-08 in Yangzhou city, Jiangsu Province, graduated from Beijing Medical University as a postgraduate in 1996,having 4 papers published.
Correspondence to Dr. Bing-Xi Zhu
, 百拇医药
Received 1996-12-28
Subject headings sulfphasalazine/pharmacology;\ colitis, ulcerative/drug therapy;\ intestinal mucosa/drug effects;\ malondialdehyde/metabolism
Abstract
AIM To substantiate the oxygen free radicals (OFR) scavenging property of sulfphasalazine (SASP) in the treatment of ulcerative colitis (UC).
, http://www.100md.com
METHODS Ten patients with active UC, 4 male and 6 female, either at first onset or during relapse, were studied. Their ages ranged from 25 to 70 years (median 40 years). The control subjects consisted of 12 patients (5 male, 7 female; age range 20～65 years) who underwent colonoscopy because of diarrhea or chronic abdominal pain. The content of colonic mucosal malondialdehyde (MDA) was measured by the thiobarbituric acid reaction in patients with UC before and after treatment with SASP and compared with that of normal colonic mucosa.
, http://www.100md.com
RESULTS The MDA content in colonic mucosa from the control group was 19.8±3.7?nmol/g.w.w. The 67.6±9.56nmol/g.w.w and 22.2±3.7nmol/g.w.w, respectively in active and remittent UC patients. The MDA content in active UC was considerably higher than that of the normal subjects (P<0.01) and the remittent UC patients (P<0.01). In remittent UC patients, the MDA content was not sigificantly different from that of the normal subjects (P>0.05).
CONCLUSION SASP is a potent OFR scavenger and its action of mechanism may be important in the treatment of UC.
, 百拇医药
INTRODUCTION
Sulfphasalazine (SASP) is widely used in the treatment of ulcerative colitis (UC). It exerts various anti-inflammatory effects, such as inhibition of the cyclooxygenase, lipoxygenase activities and various functions of inflammatory cells. Recently, SASP has been found to possess OFR scavenging properties. At the present study, we estimate the content of colonic mucosal malondialdehyde (MDA) in the patients with UC before and after treatment with SASP. The aim of this study was to confirm the OFR scavenging ability of SASP.
, http://www.100md.com
MATERIALS AND METHODS
PatientsTen patients with active UC, 4 male and 6 female, either at first onset or during relapse, were studied. Their ages ranged from 25 to 70 years (median 40 years). All patients fufilled the criteria of UC[1]. Seven patients were mild in severity, and 3 moderate. All patients remitted after given SASP for 2 to 3 months. No other drugs were prescribed during the treatment with SASP. Active and remittent UC was assessed by the criteria of Jones et al[2]. The control subjects consisted of 12 patients (5 male, 7 female, age range 20～65 years)who underwent colonoscopy because of diarrhea or chronic abdominal pain.
, 百拇医药
MethodsIn all patients, two or three biopsy specimens of the colonic mucosa were taken from inflamed mucosa of patients with active UC and from non-inflamed mucosa of patients with remittent UC, and from macroscopically normal mucosa of the control subjects. The biopsy specimens were stored immediately in liquid nitrogen. The MDA content of the tissue was measured by the thiobarbituric acid reaction[3] and expressed as nmol per one gram of wet weight tissue (nmol/g.w.w).
, 百拇医药
Statistical analysisAll values are expressed as mean±standard deviation (x±s). The paired Student′s t test was used to evaluate the difference between active UC and remittent UC group, and analyze the difference between MDA values in the UC and control groups. P<0.05 was considered significant.
RESULTS
The MDA content in colonic mucosa from control group was 19.8±3.7nmol/g.w.w, and 67.6±9.56?nmol/g.w.w and 22.2±3.7nmol/g.w.w, respectively in active and remittent UC patients. The MDA content in remittent UC patients was significantly lower than that of active UC (P<0.01), and the MDA content in remittent UC patients was not significantly different from that of the control group (P>0.05). In contrast, in the active UC it was considerably higher than that in the control group (P<0.01, Table 1).
, 百拇医药
Table 1 Comparison of content of MDA between normal and UC colonic mucosa
aP<0.01，bP>0.05， vs controls; bP<0.01， vs active UC.
, http://www.100md.com
DISCUSSION
Although the aetiology of UC remains unknown, its pathogenesis is gradually being focused on the role of OFR[4]. The presence of phagocytes is a hallmark of the active UC[5]. Large numbers of activated phagocytes pass out of the circulation and enter the inflamed mucosa and submucosa of the bowel and can produce OFR via the respiratory burst[4,6]. The main source of OFR in UC is phagocyte. Keshavarzian et al[7] and Simmonds et al[8] have demonstrated with chemiluminescence that the inflamed colons from the active UC patients or animals with experimental colitis produce much larger amounts of OFR. Direct measurment of OFR in the clinical setting is difficult, but as OFR can cause lipid peroxidation, its activity can be more easily assessed by measuring MDA, the end product of lipid peroxidation[9]. Our findings showed that the MDA content was more significantly elevated in active UC colonic mucosa as compared with the control group. Following initiation of SASP treatment, the MDA content in remittent UC colonic mucosa was considerably lower than that of active UC patients and reverted to normal levels. The present study shows that SASP is potent OFR scavengers.
, http://www.100md.com
Although SASP has been introduced into the therapy of UC for over 40 years, the mechanism of its therapeutic action is uncertain. The possibilities include inhibition of cyoclooxygenase and lipoxygenase activities[10]. In recent years, much evidence has indicated that SASP is a powerful OFR scavenger, it can scavenge O-2, H2O2, OH·, and HOCL[11]. The OFR scavenging mechanism of SASP may be important in the treatment of UC.
, 百拇医药
REFERENCES
1 The criteria of diagnosis and therapeutic effect for ulcerative colitis. Chin J Digest, 1993;13(6):354
2 Jones SC, Crabtree JE, Rembacken BJ. Mucosal interleukin-6 secretion in ulcerative colitis. Effects of anti-inflammatory drugs
and T-cell stimulation. Scand J Gastroenterol, 1994;29(6):722-728
, 百拇医药
3 Asakawa T. Thiobabituric acid test for detection lipid peroxides. Lipids, 1979;14(4):401-408
4 Simmonds NJ, Rampton DS. Inflammatory bowel disease-a radical view. Gut, 1993;34(6):865-868
5 Keshavarzian A, Fields JZ. A radical perspective on ulcerative colitis. J Gastroenterol Hepatol, 1995;10(1):208-209
6 Gross V, Arndt H, Andus T. Free radicals in inflammatory bowel disease pathophysiology and therapeutic implications.
, 百拇医药
Hepato-Gastroenterology, 1994;41(2):320-327
7 Keshavarzian A, Sedghi S, Kanofsky J. Excessive production of reative oxygen metabolites by inflamed colon: analysis
by cheniluminescence probe. Gastroenterology, 1992;103(1):177-185
8 Simmonds NJ, Allen RE. Chemiluminescence assay of mucosal reactive oxygen metabolites in inflammatory bowel
disease. Gastroenterology, 1992;103(1):186-196
, 百拇医药
9 Sedghi S, Keshavarzian A, Klamut M, Eiznhamer D, Zarling EJ. Elevated breath ethane levels in active ulcerative colitis:
Evidence for excessive lipid peroxidation. Am J Gastroenterol, 1994;89(12):2217-2221
10 Grisham MB. Oxidants and free radicals in inflammatory bowel disease. Lancet, 1994;344(24):859-861
11 Verspaget HW, Mulder TPJ, Vandersluysveer A. Reactive oxygen metabolies and colitis: A disturbed balance between damage
and protection. Scand J Gastroenterol, 1991;26(Suppl 181):44-51, http://www.100md.com
2The Third Hospital, Beijing Medical University, Beijing 100083, China
Dr. ZHU Bing-Xi, male, born on 1965-06-08 in Yangzhou city, Jiangsu Province, graduated from Beijing Medical University as a postgraduate in 1996,having 4 papers published.
Correspondence to Dr. Bing-Xi Zhu
, 百拇医药
Received 1996-12-28
Subject headings sulfphasalazine/pharmacology;\ colitis, ulcerative/drug therapy;\ intestinal mucosa/drug effects;\ malondialdehyde/metabolism
Abstract
AIM To substantiate the oxygen free radicals (OFR) scavenging property of sulfphasalazine (SASP) in the treatment of ulcerative colitis (UC).
, http://www.100md.com
METHODS Ten patients with active UC, 4 male and 6 female, either at first onset or during relapse, were studied. Their ages ranged from 25 to 70 years (median 40 years). The control subjects consisted of 12 patients (5 male, 7 female; age range 20～65 years) who underwent colonoscopy because of diarrhea or chronic abdominal pain. The content of colonic mucosal malondialdehyde (MDA) was measured by the thiobarbituric acid reaction in patients with UC before and after treatment with SASP and compared with that of normal colonic mucosa.
, http://www.100md.com
RESULTS The MDA content in colonic mucosa from the control group was 19.8±3.7?nmol/g.w.w. The 67.6±9.56nmol/g.w.w and 22.2±3.7nmol/g.w.w, respectively in active and remittent UC patients. The MDA content in active UC was considerably higher than that of the normal subjects (P<0.01) and the remittent UC patients (P<0.01). In remittent UC patients, the MDA content was not sigificantly different from that of the normal subjects (P>0.05).
CONCLUSION SASP is a potent OFR scavenger and its action of mechanism may be important in the treatment of UC.
, 百拇医药
INTRODUCTION
Sulfphasalazine (SASP) is widely used in the treatment of ulcerative colitis (UC). It exerts various anti-inflammatory effects, such as inhibition of the cyclooxygenase, lipoxygenase activities and various functions of inflammatory cells. Recently, SASP has been found to possess OFR scavenging properties. At the present study, we estimate the content of colonic mucosal malondialdehyde (MDA) in the patients with UC before and after treatment with SASP. The aim of this study was to confirm the OFR scavenging ability of SASP.
, http://www.100md.com
MATERIALS AND METHODS
PatientsTen patients with active UC, 4 male and 6 female, either at first onset or during relapse, were studied. Their ages ranged from 25 to 70 years (median 40 years). All patients fufilled the criteria of UC[1]. Seven patients were mild in severity, and 3 moderate. All patients remitted after given SASP for 2 to 3 months. No other drugs were prescribed during the treatment with SASP. Active and remittent UC was assessed by the criteria of Jones et al[2]. The control subjects consisted of 12 patients (5 male, 7 female, age range 20～65 years)who underwent colonoscopy because of diarrhea or chronic abdominal pain.
, 百拇医药
MethodsIn all patients, two or three biopsy specimens of the colonic mucosa were taken from inflamed mucosa of patients with active UC and from non-inflamed mucosa of patients with remittent UC, and from macroscopically normal mucosa of the control subjects. The biopsy specimens were stored immediately in liquid nitrogen. The MDA content of the tissue was measured by the thiobarbituric acid reaction[3] and expressed as nmol per one gram of wet weight tissue (nmol/g.w.w).
, 百拇医药
Statistical analysisAll values are expressed as mean±standard deviation (x±s). The paired Student′s t test was used to evaluate the difference between active UC and remittent UC group, and analyze the difference between MDA values in the UC and control groups. P<0.05 was considered significant.
RESULTS
The MDA content in colonic mucosa from control group was 19.8±3.7nmol/g.w.w, and 67.6±9.56?nmol/g.w.w and 22.2±3.7nmol/g.w.w, respectively in active and remittent UC patients. The MDA content in remittent UC patients was significantly lower than that of active UC (P<0.01), and the MDA content in remittent UC patients was not significantly different from that of the control group (P>0.05). In contrast, in the active UC it was considerably higher than that in the control group (P<0.01, Table 1).
, 百拇医药
Table 1 Comparison of content of MDA between normal and UC colonic mucosa
| Groups | n | MDA(nmol/g.w.w) |
| Control subjects | 12 | 19.8±3.7 |
| Active UC | 10 | 67.6±9.56a |
| Remittent UC | 10 | 22.2±3.7b |
aP<0.01，bP>0.05， vs controls; bP<0.01， vs active UC.
, http://www.100md.com
DISCUSSION
Although the aetiology of UC remains unknown, its pathogenesis is gradually being focused on the role of OFR[4]. The presence of phagocytes is a hallmark of the active UC[5]. Large numbers of activated phagocytes pass out of the circulation and enter the inflamed mucosa and submucosa of the bowel and can produce OFR via the respiratory burst[4,6]. The main source of OFR in UC is phagocyte. Keshavarzian et al[7] and Simmonds et al[8] have demonstrated with chemiluminescence that the inflamed colons from the active UC patients or animals with experimental colitis produce much larger amounts of OFR. Direct measurment of OFR in the clinical setting is difficult, but as OFR can cause lipid peroxidation, its activity can be more easily assessed by measuring MDA, the end product of lipid peroxidation[9]. Our findings showed that the MDA content was more significantly elevated in active UC colonic mucosa as compared with the control group. Following initiation of SASP treatment, the MDA content in remittent UC colonic mucosa was considerably lower than that of active UC patients and reverted to normal levels. The present study shows that SASP is potent OFR scavengers.
, http://www.100md.com
Although SASP has been introduced into the therapy of UC for over 40 years, the mechanism of its therapeutic action is uncertain. The possibilities include inhibition of cyoclooxygenase and lipoxygenase activities[10]. In recent years, much evidence has indicated that SASP is a powerful OFR scavenger, it can scavenge O-2, H2O2, OH·, and HOCL[11]. The OFR scavenging mechanism of SASP may be important in the treatment of UC.
, 百拇医药
REFERENCES
1 The criteria of diagnosis and therapeutic effect for ulcerative colitis. Chin J Digest, 1993;13(6):354
2 Jones SC, Crabtree JE, Rembacken BJ. Mucosal interleukin-6 secretion in ulcerative colitis. Effects of anti-inflammatory drugs
and T-cell stimulation. Scand J Gastroenterol, 1994;29(6):722-728
, 百拇医药
3 Asakawa T. Thiobabituric acid test for detection lipid peroxides. Lipids, 1979;14(4):401-408
4 Simmonds NJ, Rampton DS. Inflammatory bowel disease-a radical view. Gut, 1993;34(6):865-868
5 Keshavarzian A, Fields JZ. A radical perspective on ulcerative colitis. J Gastroenterol Hepatol, 1995;10(1):208-209
6 Gross V, Arndt H, Andus T. Free radicals in inflammatory bowel disease pathophysiology and therapeutic implications.
, 百拇医药
Hepato-Gastroenterology, 1994;41(2):320-327
7 Keshavarzian A, Sedghi S, Kanofsky J. Excessive production of reative oxygen metabolites by inflamed colon: analysis
by cheniluminescence probe. Gastroenterology, 1992;103(1):177-185
8 Simmonds NJ, Allen RE. Chemiluminescence assay of mucosal reactive oxygen metabolites in inflammatory bowel
disease. Gastroenterology, 1992;103(1):186-196
, 百拇医药
9 Sedghi S, Keshavarzian A, Klamut M, Eiznhamer D, Zarling EJ. Elevated breath ethane levels in active ulcerative colitis:
Evidence for excessive lipid peroxidation. Am J Gastroenterol, 1994;89(12):2217-2221
10 Grisham MB. Oxidants and free radicals in inflammatory bowel disease. Lancet, 1994;344(24):859-861
11 Verspaget HW, Mulder TPJ, Vandersluysveer A. Reactive oxygen metabolies and colitis: A disturbed balance between damage
and protection. Scand J Gastroenterol, 1991;26(Suppl 181):44-51, http://www.100md.com