Effect of D-penicillamine on rat lung elastin cross-linking during the perinatal period.
This study was designed to clarify the effects of D-penicillamine (DPA), a drug used for treatment of various pathological events, on lung elastin formation and maturation of the newborn in the perinatal period. The investigation was conducted on 20 newborn rats bred from 40 female and six male rats. DPA doses 400 mg kg(-1) day(-1) and physiological saline were given intraperitoneally (i.p) to experimental and control groups. To assess newborn maturation, their body and lung weights were determined. Serum Cu levels were measured by atomic absorption spectroscopy and ceruloplasmin (Cp) activities were measured spectrophotometrically. Newborn lung tissue elastin, desmosine (DES) and isodesmosine (IDES) levels were measured by HPLC. The results showed that DPA treatment caused loss of skin elasticity and reduction in body and lung weight in newborns of the experimental group. The serum Cu levels and Cp activity were found to be significantly lower in both maternal and newborn of the experimental groups compared with the control group. The lung DES, IDES and elastin values of newborns in the experimental group were decreased compared with the control group. In conclusion, our results indicate that 400 mg kg(-1) day(-1) DPA, a dose that is used in the treatment of Wilson's disease, rheumatoid arthritis and cystinuria, caused the retardation of newborn maturation, a decrease in DES-IDES cross-links and levels of lung elastin of offspring in the perinatal period. Another conclusion to be drawn from this study is that even low levels of Cu depletion due to DPA administration induces a change in cross-linking in lung elastin during the perinatal period.
Koçtürk
Semra
S
Biochemistry Department, Faculty of Medicine, Dokuz Eylul University, Turkey. semra.kocturk@deu.edu.tr
Oktay
Gülgün
G
Güner
Gül
G
Pekçetin
Cetin
C
Güre
Ataman
A
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002570:Ceruloplasmin / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000097:blood; D003895:Desmosine / Q000378:metabolism; D004548:Elasticity / Q000187:drug effects; D004549:Elastin / Q000378:metabolism*; D005260:Female; D007524:Isodesmosine / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000254:growth & development*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010396:Penicillamine / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D012867:Skin / Q000187:drug effects
D003895:Desmosine; D003300:Copper; D004549:Elastin; D007524:Isodesmosine; D002570:Ceruloplasmin; D010396:Penicillamine