The Effects of Cyclophosphamide and Azathioprine on Collagen in Skin and Granulation Tissue in Rats, and the Effects of Cyclophosphamide on Collagen in Human Skin

Self Cite

Granulation tissue was produced in rats by subcutaneous implantation of viscose cellulose sponges. Treatment with cyclophosphamide in a dose of 10 mg/kg/day for 14 days caused an increase in acid soluble OH-proline and a decrease in alpha/beta ratio of acid soluble collagen of granulation tissue. Forty-two days of continuous cyclophosphamide treatment caused a decrease in dry weight, in free OH-proline, and in salt soluble OH-proline in granulation tissue. These findings are in accordance with previous observations of a decreased collagen synthesis and an inhibited collagen degradation in granulation tissue after cyclophosphamide treatment. In skin, the only change after cyclophosphamide was a decrease in total content of OHproline and an increase in alpha/beta ratio of acid soluble collagen after 42 days of treatment. No effect of the subcutaneous sponge implantation was observed on the collagen variables in the skin. In comparison with unstarved controls, a reduction in dry weight and in free OH-proline in granulation tissue, as well as an increase in salt soluble OH-proline in the skin were observed 28 days after a 14-day treatment with cyclophosphamide. These observations indicate a sustained effect of cyclophosphamide on collagen 28 days after cessation of treatment. In addition the thermal stability of rat tail tendons was decreased 28 days after withdrawal of cyclophosphamide to the same extent as after starvation for 42 days and after 42 days of continuous cyclophosphamide treatment. It is concluded that the cyclophosphamide-induced collagen alterations, which may be of importance in the anti-inflammatory action of cyclophosphamide, are only in part reversible, 28 days after cessation of 14 days of cyclophosphamide treatment.

Section: Effect Of Cyclophosphamidesupporting

confidence: 81%

mentioning

confidence: 99%

Reversibility of the Effects of Cyclophosphamide on Collagen: Biochemical Studies on Skin and Granulation Tissue and Determination of Thermal Stability of Tail Tendons of Rats

Hansen

Lorenzen

1978

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“…tion in the treatment of immunological and inflammatory diseases in addition t o being a frequently used antineoplastic agent (Stevens & Willoughby 1969;Currey 1971;Hill 1975). T h e effects o n connective tissue have, therefore, attained increasing interest in experimental work with this compound (Bagley et al 1973, Hansen & Lorenzen 1975.…”

mentioning

confidence: 99%

Synthesis and Solubility of Collagen in Rats during Recovery after High‐dose Cyclophosphamide Administration

Wie

Beck

1981

The metabolism of collagen and mineral was studied during a nine‐day postmedicational period in young, male rats receiving high‐dose intraperitoneal cyclophosphamide treatment every second day for 12 days. Two days after ending medication the white blood cell counts (WBC) were reduced by about 70%. Both synthesis and solubility of collagen were suppressed by the present medication 2 days after termination of treatment. This suppression continued throughout the 9‐day postmedicational period in bones, whereas in connective tissue of porous, ceramic implants both total collagen and the amount of salt soluble collagen regained normal values 9 days after cessation of treatment. Increased mineralization was found 2 days after ending medication and this high degree of mineralization persisted during the postmedicational period studied. Serum albumin levels were reduced and no increases were detected during the postmedicational period. The suggestion is made that the general protein synthesis is affected by high‐dose cyclophosphamide administration.

“…Effects by the drug on the hydroxylation of proline have been suggested by Hansen & Lorenzen (1975), but are not likely to be of any significance in the present context as stable, extracellular collagen is not formed without at least 90% hydroxylation (Prockop et a/. 1979).…”

Section: Discussionmentioning

confidence: 83%

“…The main target of activated cyclophosphamide is supposed to be the guanine bases of the DNA molecule, leading to cross-link formation between the double helices and impaired replication (Brock & Hohorst 1963& 1967. Some reports, however, suggest that alkylating agents may change the activities of enzymes involved in amino acid metabolism (Hill 1975) or exercise a direct influence o n structural proteins (Dorner & Uddin 1968;Hansen & Lorenzen 1975).…”

mentioning

confidence: 99%

Effects of Cyclophosphamide on the Formation and Solubility of Collagen

Wie

Beck

1981

The effects of low (5 mg/kg × 7) and high (20 or 30 mg/kg × 7) doses of cyclophosphamide on the formation an solubility of collagen in subcutaneous, porous implants, bones and incisional skin wounds were studied in young, male rats. At the 5 mg/kg schedule, effects from the drug were only detected as an increased solubility of collagen in implant connective tissue. At the 20 mg/kg schedule, there was a significant reduction of the synthesis and solubility of collagen in bones and in skin wounds. The 30 mg/kg schedule significantly depressed all the parameters studied except the specific activity of hydroxyproline in implants. Collagen stability seems to be impaired at low dose levels, whereas one of the main effects of high doses appears to be inhibition of collagen synthesis.