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 ::  Abstract
 ::  Introduction
 ::  Material and methods
 ::  Results
 ::  Discussion
 ::  References
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Year : 1989  |  Volume : 35  |  Issue : 4  |  Page : 199-203

Immunotherapeutic modulation of intraperitoneal adhesions by Asparagus racemosus.




Correspondence Address:
N N Rege


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Source of Support: None, Conflict of Interest: None


PMID: 0002641519

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 :: Abstract 

The hypothesis that macrophages appear to play a pivotal role in the development of intraperitoneal adhesions and that modulation of macrophage activity, therefore, is likely to provide a tool for prevention of adhesions, was tested in the present study. Effect of Asparagus racemosus, an indigenous agent with immunostimulant properties, was evaluated in an animal model of intraperitoneal adhesions induced by caecal rubbing. Animals were sacrificed 15 days following surgery. The peritoneal macrophages were collected to assess their activity. At the same time, peritoneal cavity was examined for the presence of adhesions, which were graded. A significant decrease was observed in the adhesion scores attained by animals receiving Asparagus racemosus. This was associated with significant increase in the activity of macrophages (70.1 +/- 2.52), compared to that in surgical controls (53.77 +/- 10.8). These findings support our hypothesis and provide a novel approach for the prevention and management of post-operative adhesions.


Keywords: Adhesions, Adjuvants, Immunologic, pharmacology,Animal, Cecal Diseases, prevention &control,Female, Macrophage Activation, drug effects,Male, Peritoneal Diseases, prevention &control,Plants, Rats,


How to cite this article:
Rege N N, Nazareth H M, Isaac A A, Karandikar S M, Dahanukar S A. Immunotherapeutic modulation of intraperitoneal adhesions by Asparagus racemosus. J Postgrad Med 1989;35:199-203

How to cite this URL:
Rege N N, Nazareth H M, Isaac A A, Karandikar S M, Dahanukar S A. Immunotherapeutic modulation of intraperitoneal adhesions by Asparagus racemosus. J Postgrad Med [serial online] 1989 [cited 2018 Sep 24];35:199-203. Available from: http://www.jpgmonline.com/text.asp?1989/35/4/199/5684





 :: Introduction Top


Serious morbidity due to intraperitoneal adhesions is frequently encountered in surgical practice.[15],[22] Various etiological factors viz., bleeding, trauma to viscera, serosal injuries, infection, foreign body deposition like talc powder and ischaemia are incriminated in development of adhesions.[8] Apparently though these etiologies appear diverse, deposition of fibrin is always an essential step in the pathophysiology of adhesion formation. Whether the fibrinous exudate will undergo complete dissolution or will be converted to fibrous strand, entirely depends on the concentration of endogenous proteolytic enzymes[10] and interaction of cells e.g., mast cells, eosinophils, macrophages and fibroblasts.[2],[13],[19] The key cells regulating the complex process of fibrosis appear to be the macrophages.[7] These cells not only phagocytose the cellular debris and modulate the nonspecific, early inflammatory phase of adhesion formation, but also affect the fibroproliferative response.[11] The secretory products of these cells are capable of degrading the collagen and proteoglycan matrix.[20]

Modulation of activity of macrophages, therefore could be an important means of preventing adhesions. The present study was carried out to investigate the state of activity of macrophages in an animal model of intraperitoneal adhesions. The macrophages can be activated by a number of exogenously administered biological products and chemical substances.[6] To evaluate whether modulation of macrophage activity prevents adhesion formation, Asparagus racemosus, a plant with rasayana properties was selected.[18] This plant has been shown to increase the activity of rat peritoneal macrophages.[3] It was, therefore, of interest to study its effect on peritoneal adhesions.


 :: Material and methods Top


The study was carried out in albino rats of either sex, weighing between 100 and 120 gm. These animals were divided into 5 groups as follows:

Group I: Eight animals received only vehicle and served as normal controls.

Group II: Eight rats were given 200 mg/ kg of Asparagus racemosus as total extract, orally every day for 15 days.

Group III: Surgical procedure was carried out in 12 animals to induce intraperitoneal adhesions. These animals received only vehicle following surgery and served as surgical controls.

Group IV: Nine animals were pretreated with Asparagus racemosus for 15 days, following which intraperioneal adhesions were induced. The treatment was continued after surgery.

Group V: Seven animals belonging to this group received Asparagus racemosus from the day of surgery. The therapy was continued for 15 days.

Surgical technique

Intraperitoneal adhesions were induced as per the method described by Sachdev et al.[16] Rats were anaesthetized with pentobarbitone sodium; laparotomy was performed. Caecum was delivered out gently through the incision and approximately an area of 1 cm diameter over the caccal wall was rubbed with a cotton gauze piece, wrapped around an index finger. Rubbing was continued till the punctuate haemorrhages appeared. Caecum was replaced back into the abdominal cavity and abdominal incision was sutured in two layers with chromic catgut (No. 4.0) and black silk (No. 3.0 respectively.

Evaluation of macrophage activity

Animals from Gr. I and II were sacrificed after 15 days of vehicle or drug therapy. The rest of the animals were sacrificed on the 15th day after surgery. The abdominal cavity was opened through an another incision made in the left flank. A lavage with minimum essential medium (MEM) was given to collect peritoneal macrophages. Activity of the harvested macrophages was determined with the help of a phagocytic assay technique using S. aureus as the test organism.[21] The phagocytic activity was expressed as lye phagocytosis.

Assessment of adhesions

After the collection of macrophages, the incision was further extended in Gr. III, IV and V. A search was made for the presence of adhesions. Severity of adhesions was decided by attributing the grades to number, character and area involved as shown in[Table - 1].

A score was developed for each animal by adding up the grades assigned for individual attribute. The maximum score that could be obtained by an animal was 9. Assessment was done by a research fellow, who was unaware of treatments received by different groups.

The data was analysed using Student's `t' test and Mann Whitney test.


 :: Results Top


The results of the study are illustrated in Fig. 1. The peritoneal macrophages obtained from the normal rats exhibited 32 1.77% phagocytosis. The animals receiving Asparagus racemosus (Gr. II) showed a significant increase in the phagocytic activity (53 5.78%) of macrophages (p < 0.05).

The animals which underwent surgery (Gr. III) developed considerable adhesions on the 15th day after surgery. These adhesions were scored and the pattern of score distribution for this group is depicted in Fig. 1 [Figure - 1]. The macrophages isolated from the peritoneal cavity of these animals also showed on increase in the activity (53.77 10.8%) as compared to normal (p<0.05).

Pretreatment with Asparagus racemosus (Gr. IV), however, decreased the incidence of adhesion formation. The adhesions when encountered in these animals, were thin and involved smaller area. The distribution pattern of score attained by this group corroborates this fact [Figure - 1]. When compared with the Gr. III, all the three attributes of adhesion viz., number, character and area involved were found to be significantly less (a = 0.05). The percentage phagocytosis of macrophages was 70.1 2.52. This activity was greater than that of Gr. III (p < 0.05).

The animals which received treatment following induction of adhesions (Gr. V) also exhibited similar response. The development of adhesions was significantly inhibited (a = 0.05) and this was associated with increased phagocytic activity of peritoneal macrophages (68.5 4.2; ) (p < 0.05).


 :: Discussion Top


Precise knowledge of key events in the pathogenesis of disease and selection of a suitable animal model which reproduces most of the features of the condition, are the prerequisites for evaluation of any therapeutic agent, intraperitoneal adhesions being no exception. In the present study, the adhesions were induced by rubbing the wall of the caecum by a gauze piece. This causes drying of serosa and oozing of blood, simulating the two relatively minor, yet common accidents, that may occur during abdominal surgery in humans, leading to development of adhesions.[9] Three phases are discernible in the evolution of adhesions viz., (1) degeneration and desquamation of mesothelial cells (0-7 hours), (2) exudation and deposition of fibrin (7 hours-10 days) and (3) transformation of fibrinous bands to fibrous tissue (10 days-1 month)[12] It has been reported that macrophages infiltrate the serofibrinous exudate within the first 24 hours of trauma, increase in number and mature during following days and a few of them may remain at the site 15 days later, inspite of conversion of fibrinous strands to fibrous ones.[13]

In our model, the activity of macrophages isolated from the peritoneal cavity, 15 days following surgery, was found to be higher than in the normal animals. However, the presence of adhesions in this group suggests that this increase in the activity may be a result of an early inflammation which precedes fibrous tissue deposition. The macrophages digest the cellular debris during the process of inflammation and undergo stimulation by the mediators released by other cells at the site e.g. lymphocytes.[4] The proliferation of fibroblasts and collagen deposition is the end result of this increased activity.[5],[12]

The animals receiving Asparagus racemosus showed a significant increase in macrophage phagocytosis and when these pretreated animals underwent surgery, further increase in the activity of macrophages was observed on the 15th post-operative day. At the same time, the adhesions were significantly less. Same picture was seen with the group which received post-operative therapy. This indicates that macrophages stimulated beyond certain limits, can prevent adhesion formation.

Such bidirectional regulation of collagen deposition by macrophages is possible and has been demonstrated previously for alveolar macrophages.[1]

It seems that following administration of Asparagus racemosus, the ability of macrophages to function efficiently increases. In other words, the macrophages undergo 'activation'. This activation was assessed in the present study in terms of phagocytic activity of cells, which is one of the indices of activation.[14] The activated macrophages are known to secrete wide range of biologically active products;[20] which are barely released by the unstimulated cells. These compounds are capable of affecting the various steps in pathogenesis of adhesions [Figure - 2].

The protection offered by Asparagus racemosus may be due to the amplification of secretory activities of macrophages. This must have provided suppressive signal to fibroblasts and have attenuated the process of fibrosis.



 
 :: References Top

1.Clark, I. G. and Greenberg, J.: Modulation of effects of alveolar macrophages on lung fibroblast collagen production rate. Amer. Rev. Resp. Dis., 135: 52-56, 1987.   Back to cited text no. 1    
2.Connolly, J. E. and Smith, J. W.: The prevention and treatment of intestinal adhesions. Int. Obstr. Surg. In, Surg. Gynaecol. & Obstet., 110: 417-431, 1960.  Back to cited text no. 2    
3.Dahanukar, S., Thatte, U., Pai, N., More, P. B. and Karandikar, S. M.: Protective effects of Asparagus racemosus against induced abdominal sepsis. Indian Drugs, 24: 125-128, 1986.  Back to cited text no. 3    
4.Dannenberg, A. M.: Macrophages in inflammation and infection. New Engl. J. Med., 293: 489-493, 1975.  Back to cited text no. 4    
5.DeLustro, F., Sherer, G. K. and LeRoy, E. C.: Human monocyte stimulation of fibroblast growth by soluble mediator (s). J. Reticuloendothel. Soc., 28: 519-532, 1980.  Back to cited text no. 5    
6.Drews, J.: Immunomodulation, In, "Recent Advances in Infection" No. 2, Edt. D. S. Reeves and A. M. Geddes. Churchill Livingstone, London, 1982, pp. 89-99.   Back to cited text no. 6    
7.Elias, J. A., Rossman, M. D., Zurier, R. B. and Daniele, R. P.: Human alveolar macrophage inhibition of lung fibroblast growth. Amer. Rev. Resp. Dis., 131: 94-99, 1985.  Back to cited text no. 7    
8.Ellis, H.: The cause and prevention of post-operative adhesions. Surg. Gynecol. & Obstet., 133: 497-511, 1971.  Back to cited text no. 8    
9.Graeme, B. R.: Post-operative peritoneal adhesions: a study of the mechanisms. Amer. J. Pathol., 65: 117-148, 1971.  Back to cited text no. 9    
10.Knighley, J. J., Agostino, D. and Cliff ton, E. E.: The effect of fibrinolysis and heparin on the formation of peritoneal adhesions. Surgery, 52: 251-258, 1962.   Back to cited text no. 10    
11.Korn, J. H., Halushka, P. V. and LeRoy, E. C.: Mononuclear cell modulation of connective tissue function: suppression of fibroblast growth by stimulation of endogenous prostaglandin production. J. Clin. Invest., 65: 543-554, 1980.  Back to cited text no. 11    
12.Leibovlch, S. J. and Ross, R.: A macrophage dependent factor that stimulates the proliferation of fibroblasts in vitro. Amer. J. Pathol., 84: 510-513, 1976.  Back to cited text no. 12    
13.Milligan, D. W. and Raftery, A. T.: Observations on the pathogenesis of peritoneal adhesions: a light and electron microscopic study. Brit. J. Surg., 61: 274-280, 1974.  Back to cited text no. 13    
14.North, R. J.: The concept of the activated macrophage. J. Immunol., 121: 806-808, 1978.  Back to cited text no. 14    
15.Raf, L. E.: Causes of small intestinal obstruction; a study covering the Stockholm area. Acto Chir. Scandinav., 135: 67-72, 1969.  Back to cited text no. 15    
16.Sachdeva, H. S., Gutierrez, L. V. and Cox, G. A.: Silicone fluid and steroids in the prevention of adhesions. Brit. J Surg., 58: 382-384, 1971.  Back to cited text no. 16    
17.Schade, D. S. and Williamson, J. R.: The pathogenesis of peritoneal adhesions. Ann. Surg., 167: 500-510, 1968.  Back to cited text no. 17    
18.Sushruta Su. No. 7. In, "Sushruta Samhita, Chapter 1. 2nd Edition. Editor: Vaidya, J. T. Acharya, Pandurang Jawaji, Nirnayasagar Press, 1931, p. 3.  Back to cited text no. 18    
19.Tiwari, A. K.: Role of mast cells in the aetiopathogenesis of post-operative abdominal adhesions. Ind. J. Surg., 49: 163-172, 1987.  Back to cited text no. 19    
20.Unanue, F. R.: Secretory function of mononuclear phagocytes. Amer. J. Pathol., 83: 396-417, 1976.  Back to cited text no. 20    
21.VanFurth, R., Theda, L. and Leijh, P. C. G.: In vitro determination of phagocytosis and intracellular killing by polymorphonuclear and mononuclear phagocytes. In "Handbook of Experimental Immunology" Vol. 2, Editor: D. M. Weir, Blackwell Scientific Publ., London, 1978, pp. 32.1-32.7.  Back to cited text no. 21    
22.Wangensteen, O. H.: Historical aspects of the management of acute intestinal obstruction. Surgery, 65: 363-383, 1969.  Back to cited text no. 22    


    Figures

[Figure - 1], [Figure - 2]

    Tables

[Table - 1]

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Online since 12th February '04
2004 - Journal of Postgraduate Medicine
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