Metallothionein attenuates carmustine-induced oxidative stress and protects against pulmonary fibrosis in rats.
The present study was carried out to evaluate the effect of exogenously administered metallothionein (MT) against carmustine (BCNU)-induced lung toxicity in rats. A total of 60 rats were randomly divided into four groups (15/group): control group in which the animals received 0.5 ml physiologic saline containing 10% ethanol (IP) weekly, MT-administered group in which rats received MT (30 micromol/kg, IP) weekly, BCNU-administered group in which rats received BCNU (5 mg/kg, IP) weekly and MT + BCNU group in which rats received weekly doses of BCNU (5 mg/kg, IP) followed 24 h later by MT (30 micromol/kg, IP). At the end of the experiment (after 6 weeks), lung histological changes, collagen staining, the activity of glutathione reductase (GR) and contents of reduced glutathione (GSH) and hydroxyproline (Hpr) in the lung as well as serum level of tumor necrosis factor-alpha (TNF-alpha) were evaluated. The obtained data revealed that BCNU induced pathological changes and markedly increased lung collagen and level of Hpr but decreased GSH content and GR activity and increased serum TNF-alpha compared to both control and MT-administered rats. Administration of MT + BCNU markedly improved histological features and decreased staining of collagen along with increased GR activity, GSH content but decreased level of Hpr in lung tissue as well as decreased serum level of TNF-alpha compared with BCNU-treated rats. Based on our results, it is possible to postulate that exogenous MT can act against BCNU-induced lung toxicity by a mechanism related, at least in part, to its ability to decrease oxidative stress and fibrosis.
Department of Pharmacology, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia. goudahelal@gmail.com
Gouda Kamel
GK
Helal
Omayma K
OK
Helal
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity; D002330:Carmustine / Q000633:toxicity*; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism; D006909:Hydroxyproline / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000187:drug effects
D018906:Antineoplastic Agents, Alkylating; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D008668:Metallothionein; D005980:Glutathione Reductase; D005978:Glutathione; D006909:Hydroxyproline; D002330:Carmustine