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Experimental and Clinical Pharmacology 2003 Vol. 66, No. 6, pp. 48-49

Anti-inflammatory Activity of Mebavin, A New Water-Soluble Derivative of

Gossypol

F.M.Sabirova, A.A. Madaminov

Investigation of the effect of mebavin on the adjuvant arthritis showed that this water-

soluble derivative of gossypol (preparation dosage of 100 µ g/kg) possesses an anti-inflammatory activity comparable with that of prednasolone.

Key Words: Gossypol derivatives, mebavin, prednasol, adjuvant arthritis, anti-

inflammatory effect

Introduction

Inflammation occurs as a universal reaction of organisms to various agents, including

allergens. Gossypol derivatives, besides primary immunodepressive action, also possessanti-inflammatory effects. Linked together, mebavin, a new water-soluble derivative of

gossypol, are shown to work to study anti-inflammatory action of one model of adjuvant

arthritis (AA), which present a majority produce an occurrence of single from mostfollow model of inflammation.

Experimental Methods

Utilization of water-soluble mebavin, creation of Institute of Bioorganic Chemistry,

Academy of Science, Republic of Uzbekistan, and introduce a compound combining one part lipophyllic batriden [2] and 9 parts hydrophyllic carrier, polyvinylpyrrolidone,molecular mass 12,600. It is an amorphous powder of an orange color, with a slight

specific smell, hygroscopic, dissolves well in water and alcohol, that promotes an

increase of its biological accessibility.

Experiments were conducted half on 104 Vistar rats, weighing 200-250 grams, and half

on 150 inbred mice, 3-4 months of age of line SVA with final body mass of 18-25 grams.Maintenance of animals accomplished in accordance with regulations, adopting European

conventions for protection of experimental animals, utilization of experimental and its

series (Straβ burg, 1986).

Adjuvant arthritis (AA), complete adjuvant (PAF) provided for animals, with the help of

our friends at the firm Sigma (U.S.A.). For rats with AA, were given a one-time

subcutaneous shot of 1 milligram PAF introduced at the base of leg, maintenance of 5milligrams BCG per milligram (1milligram/ rat). For mice in AA study, were given

single introduction of PAF in hind leg (0.2 milligram/mouse).

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1 Department of Experimental Medicine and Pathological Anatomy (Director- Professor

M.D. Urazmetova) State Science Center of Emergency Medicine, Republic of

Uzbekistan, Tashkent, 700107, Farhod Street 2

Arthritis evaluated objectively (volumetrically) and subjectively (visually) in this way up

to induction of AA and then afterwards every 7 days after onset of illness in the course of 38-60 days. Volumetric method consisting of immersing affected paw of rat in vessel

with mercury. Change recorded in condition of individual (conditional units) depending

on size of capillary displacement over air ball, connecting two vessels. Then calculatedinhibition of swelling corresponding with the AA period. Visual degree of swelling in

extremity of animal estimated by following scheme: (-)-absence of margin, (+)- redness,

small margin; (++)- redness, average swollenness, skin stretched; (+++)- intense

swelling, transience of joint articulation, fingernail stretched.

Study of effects of mebavin, prednasol, and also their combinatory utilization on animals

with AA. Prepare animal’s intake every day in afternoon inducing pathological processes

until end of experiment with following dosages: mebavin- 100 milligrams/kilogram/dayinternally, prednasolone- 30 milligrams/kilogram/day subcutaneously. Since the object

of combinatory therapy appears to achieve therapeutic synergistic effects and reducestoxicity, dose daily from preparation, reduce by 2 times and working out calculation of 50

and 15 milligrams/ kilogram. Concerning toxicity of combinatory application judging by

their affect on general weight and mortality.

Experimental results were processed statistically by utilizing criteria by Student and

Wilkinson- Mann- Whitney [1].

Results and Discussion

What is apparent from their tabulation, in mice with AA without treatment, average sizelesion on hind leg compiled 323.3 conditional units during all days of observation were

statistically reliably increased compared with the other group of animals, with a small

pronouncement expressed on 14-28 days of illness – 299.7 +/- 6.2 ÷ 377.1 +/- 5.5conditional units (P1< 0.05).

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Effectiveness of mebavin, prednasolone and their combinatory use, by degree of swelling

(%), hind extremity of strain CVA mice with adjuvant arthritis (estimated by “+++”).

↑AA- adjuvant arthritis; M- AA + prednasolone; MP- AA + mebavin + prednasolone.

Over abscissa- days observed; over ordinal- degree swelling, %.

Degree of swelling of hind leg of rats with adjuvant arthritis (AA) with treatment with

mebavin, prednasolone, and also their combinatory application.

Margin of Period of Treatment Number of Animals Average Size

Inhibition Animal Health Hind Extremity

of rat, conditionof individuals

AA; AA + mebavin; AA + prednasolone; AA + mebavin + prednasolone

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↑Comments. Differences in reliability of relative evidence: * - Animal health (control)(P1<0.05); **- Rats with AA for corresponding period of treatment (P2<0.05).

Volumetric analysis demonstrated that mebavin of dose of 100 milligrams/kilogram for all period of study inhibits swelling to 8.4-29.4% and prednasolone – 5.3-34.7%. The

most depression was able to be achieved by combinatory application of mebavin and

prednasolone (5.8-40.8%), with maximal suppression of swelling by 35 days (at stage peak of illness with AA) (P2<0.05). In comparison with appropriate period of

investigation and swollenness of extremity of rat with AA without treatment and by

combinatory application of mebavin and prednasolone showing statistically reliable

difference between comparisons revealed by 21,28, 35 days of experiment (P2 <0.05) .

Minimal loss of body weight and low mortality among rats given groups evidencing basetoxicity of studied medicines.

With following series of experiments studied influence preparation of individually and of

combination by degree of swelling of hind extremity of strain CVA mice. The

medications were given to the indicated animals with AA, in the same dosages asindicated in previous experiments.

Visual observation over condition of extremity of animals (7-21 days) showed that it wasdeveloped by 100% of all mice. Average showed maximal swelling, estimated by “+++”

membership 87.5%, with highest indicator on 21st day (95%), figure.

Mebavin inhibited swelling maximally by average of 52.1%, prednasolone by 46.3%,mebavin + prednasolone, by 39.4%. The most suppression in every group recorded at the

end of observation, on 28th day.

In this series the most depression that is able to be achieved by combinatory application

of mebavin and prednasolone, which indicates synergism acting between the drugs.

Conclusion

Mebavin possessed anti-inflammatory activity and its treatment compared to

prednasolone. Combinatory application of mebavin with prednasolone driven bysynergism of their action, reducing toxicity applying preparation and potential anti-

inflammatory effects.

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Literature

1. E.V. Gubler, Deducing methods of analysis for identifying pathological

processes, Medicine, Moscow (1978).

2. M.D. Mashkovsky, Medicinal Remedies, 13(2), Medicine, Tashkent(1998),p.208.

3. A. Fossati, Drugs Under Experimental and Clinical Research, 25(6), 263-270(1999).

4. E. Mazzon, I. Serraino, J.H. Li, L. Dugo, et al. European Journal of Pharmacology, 415(1),85-94 (2001).

Received 12.08.02

Antiinflammatory Activity of Mebavin, A New Water-Soluble Derivative of GossypolF.M. Sabirova and A.A. Madaminov, Department of Experimental Medicine and

Pathological Anatomy, State Center of Emergency Medicine, Farhod Street 2, Tashkent,

700107 Uzbekistan

Investigation of the effect of mebavin on the adjuvant arthritis showed that this water-

soluble derivative of gossypol possesses an anti-inflammatory activity comparable withthat of prednasolone.

Translation by Kristina Turner

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