Metabolism of glycosaminoglycans in tissues of adjuvant arthritic rat.

The metabolic changes in the connective tissue glycosaminoglycans were studied in tissues of adjuvant induced arthritic rats. Arthritic process was induced in rats with the inoculation of Freund's adjuvant containing heat killed Mycobacterium tuberculosis in paraffin oil. The connective tissue glycosaminoglycans were fractionated into sulfated and non-sulfated glycosaminoglycans by chemical and enzymatic methods. The biosynthesis of sulfated glycosaminoglycans was examined using radioactive labeled (35S)-sulfate incorporation measurements into the sulfated glycosaminoglycans in tissues such as liver, kidney, spleen and skin of arthritic rats. The catabolism of glycosaminoglycans was studied by measuring the activity of various connective tissue degrading lysosomal glycohydrolases in tissues of experimental animals. In addition, the changes in the contents of total glycosaminoglycans, mono-sulfated, highly-sulfated and non-sulfated glycosaminoglycans were quantitatively assessed in diseased tissues. Alterations in the metabolism of connective tissue glycosaminoglycans were demonstrated in tissues of arthritic rats. The uptake of (35S)-sulfate into the tissue was found to be increased in liver, kidney and spleen, while that of skin decreased during the process of arthritis. The total glycosaminoglycan content was significantly elevated in diseased tissues compared to normal. Similarly, mono-sulfated, highly-sulfated and non-sulfated glycosaminoglycans were found to be increased in arthritic tissues. In addition, the activity of various connective tissue degrading lysosomal glycohydrolases such as beta-glucuronidase, beta-N-acetylglucosaminidase, cathepsin B, cathepsin L and collagenolytic cathepsin was increased in tissues of arthritic rat. The results presented in this communication indicate that the characteristic alterations were induced in the metabolism of glycosaminoglycans by the dynamic process of adjuvant arthritis.