Studies on the effect of 3,4-dehydroproline on collagen metabolism in carbon tetrachloride-induced hepatic fibrosis

Kerwar, S.S.; Oronsky, Arnold L.; Choe, David; Álvarez, Beatriz

doi:10.1016/0003-9861(77)90289-2

Cited by 8 publications

(4 citation statements)

References 25 publications

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“…The administration of DHP during the developing phase of DOCA-salt hyperten sion prevents aortic hypertrophy and, since the compound has general effects on collagen synthesis in the body [5][6][7], presumably it prevents hypertrophy throughout the arterial tree. However, because DHP fails to prevent the rise in blood pressure, we cannot support the suggestion [2] that a new approach to the reduction of blood pressure in hypertension might be developed from agents able to sup press excess arterial connective tissue deposi tion in this disease.…”

Section: Discussionmentioning

confidence: 99%

“…The net effect of DHP is to produce a deficiency of correctly processed, fully functional collagen in hyper trophic tissues [5][6][7], In addition, DHP par tially inhibits the biosynthesis of non-collagenous proteins [5,18]. If.…”

Section: Discussionmentioning

confidence: 99%

“…This suggestion, if it is true, indicates a possible new approach to the treatment of hypertension based on the inhi bition or reversal of excess connective tissue deposition in the arteries. However, before undertaking a search for novel agents with such actions it seemed prudent to examine more closely the antihypertensive action of BAPN and also to study the effects in hyper tensive animals of 3,4-dehydroproline (DHP) which has been shown to be an effec tive inhibitor of collagen deposition in vivo in the uterus [5], fibrotic liver [6] and fibrotic lungs [7], Our results indicate that the inhibi tion of hypertension-induced vascular hyper trophy by DHP is not antihypertensive. Fur thermore, an antihypertensive action of BAPN is spontaneously hypertensive (SH) rats and rats with renal hypertension is evi dent before any effect on aortic hypertrophy.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Inhibitors of Collagen Maturation on Hypertension in Rats

Franklin¹,

Morris²,

Loveday³

1982

J Vasc Res

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The effects of β-aminopropionitrile (BAPN), an inhibitor of collagen maturation, have been examined in three models of hypertension in rats. It is shown for the first time that BAPN has a rapidly developing antihypertensive action in rats with renal (one kidney-one clip) hypertension. The compound also lowered blood pressure in spontaneously hypertensive rats. In both these experiments although BAPN lowered blood pressure it did not affect the hypertension-induced hypertrophy of the aorta. BAPN suppressed the rise in blood pressure during the developing phase of deoxycorticosterone acetate-salt-induced hypertension and in this model the compound also prevented the accompanying aortic hypertrophy. However, another inhibitor of collagen synthesis and maturation, 3,4-dehydroproline, completely suppressed aortic hypertrophy but failed to prevent the rise in blood pressure in deoxycorticosterone acetate-salt hypertension. It is concluded that: (1) BAPN may have a direct antihypertensive action, and (2) inhibition of aortic hypertrophy alone cannot prevent the rise in blood pressure in the developing phase of deoxycorticosterone acetate-salt hypertension.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of Inhibitors of Collagen Maturation on Hypertension in Rats

Franklin¹,

Morris²,

Loveday³

1982

J Vasc Res

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“…Proline analogs have been used as inhibitory agents of collagen synthesis (3)(4)(5)(6). They are incorporated into the collagen molecule to form the nonhelical protein which is degraded easily, and consequently to inhibit collagen accumulation (7).…”

mentioning

confidence: 99%

Decreased collagen accumulation by a prolyl hydroxylase inhibitor in pig serum-induced fibrotic rat liver

et al. 1988

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Hepatic fibrosis was induced in rats by repeated i.p. injections of pig serum. The hepatic hydroxyproline content increased to 2.1 times the normal control level at 6 weeks and to 3.2 times at 10 weeks. When P-1894B, an inhibitor of prolyl hydroxylase, was administered, there was a dose-dependent inhibition of the increase to nearly normal control levels at 6 and 10 weeks. There was also by histology a dose-dependent reduction in the degree of hepatic fibrosis. Hepatocellular damage was minimal and its extent did not vary with the degree of fibrosis or the treatment. P-1894B dose dependently reduced the hydroxylation of peptidyl proline in the fibrotic liver. These data suggest that P-1894B inhibited hepatic fibrogenesis by direct action on collagen but not by protection against hepatocellular damage leading to collagen formation. A prolyl hydroxylase inhibitor may be a candidate for use in treatment of hepatic fibrosis.

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Effects of bleomycin on ¹⁴C‐proline uptake, its incorporation into proteins and hydroxylation in collagenous proteins of hamster lung slices

Giri

Younker

Schiedt

1985

J of Applied Toxicology

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The uptake of 14C-proline by lung slices and its incorporation into trichloroacetic-acid (TCA)-insoluble proteins and hydroxylation in collagenous proteins were studied. They were found to be linearly increased with the incubation time for as long as 8 h. The effects of different concentrations of bleomycin on these parameters were subsequently investigated. Bleomycin at 10(-3) M significantly reduced the uptake of 14C-proline to 75% of the control value. The incorporation of 14C-proline into TCA-insoluble proteins was reduced to 84%, 78% and 75% of the control at 2.5 X 10(-4) M, 5 X 10(-4) M and 10(-3) M concentrations of bleomycin, respectively. Bleomycin failed to alter the proline pool size of the lung slices at any of these concentrations. In addition, bleomycin also inhibited the hydroxylation of 14C-proline into collagen to 72% and 69% of the control at 5 X 10(-4) M and 10(-3) M, respectively. These findings show that bleomycin-induced increases in collagen synthesis in vivo is probably secondary to inflammatory reactions of the lung and bleomycin per se has little effect on increased collagen synthesis responsible for lung fibrosis.

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Studies on the effect of 3,4-dehydroproline on collagen metabolism in carbon tetrachloride-induced hepatic fibrosis

Cited by 8 publications

References 25 publications

Effects of Inhibitors of Collagen Maturation on Hypertension in Rats

Effects of Inhibitors of Collagen Maturation on Hypertension in Rats

Decreased collagen accumulation by a prolyl hydroxylase inhibitor in pig serum-induced fibrotic rat liver

Effects of bleomycin on ¹⁴C‐proline uptake, its incorporation into proteins and hydroxylation in collagenous proteins of hamster lung slices

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Studies on the effect of 3,4-dehydroproline on collagen metabolism in carbon tetrachloride-induced hepatic fibrosis

Cited by 8 publications

References 25 publications

Effects of Inhibitors of Collagen Maturation on Hypertension in Rats

Effects of Inhibitors of Collagen Maturation on Hypertension in Rats

Decreased collagen accumulation by a prolyl hydroxylase inhibitor in pig serum-induced fibrotic rat liver

Effects of bleomycin on 14C‐proline uptake, its incorporation into proteins and hydroxylation in collagenous proteins of hamster lung slices

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Effects of bleomycin on ¹⁴C‐proline uptake, its incorporation into proteins and hydroxylation in collagenous proteins of hamster lung slices