Single high dose dexamethasone treatment decreases the pathological score and increases the survival rate of paraquat-intoxicated rats.
Dexamethasone (DEX), a synthetic corticosteroid, has been successfully used in clinical practice during paraquat (PQ) poisonings due to its anti-inflammatory activity, although, as recently observed, its effects related to de novo synthesis of P-glycoprotein (P-gp), may also strongly contribute for its healing effects. The main purpose of this study was to evaluate the effects of a single high dose DEX administration, which induces de novo synthesis of P-gp, in the histological and biochemical parameters in lung, liver, kidney and spleen of acute PQ-intoxicated rats. Four groups of rats were constituted: (i) control group, (ii) DEX group (100 mg/kg i.p.), (iii) PQ group (25mg/kg i.p.) and (iv) PQ+DEX group (DEX injected 2h after PQ). The obtained results showed that DEX ameliorated the biochemical and histological lung and liver alterations induced by PQ in Wistar rats at the end of 24 hours. This was evidenced by a significant reduction in lipid peroxidation (LPO) and carbonyl groups content, as well as by normalization of the myeloperoxidase (MPO) activities. Moreover, DEX prevented the increase of relative lung weight. On the other hand, these improvements were not observed in kidney and spleen of DEX treated rats. Conversely, an increase of LPO and carbonyl groups content and aggravation of histological damages were observed in the latter tissues. In addition, MPO activity increased in the spleen of PQ+DEX group and urinary N-acetyl-beta-D-glucosaminidase activity, a biomarker of renal tubular proximal damage, also augmented in this group. Nevertheless, it is legitimate to hypothesize that the apparent protection of high dosage DEX treatment awards to the lungs of the PQ-intoxicated animals outweighs the increased damage to their spleens and kidneys, because a higher survival rate was observed, indicating that DEX treatment may constitute an important and valuable therapeutic drug to be used against PQ-induced toxicity.
Dinis-Oliveira
R J
RJ
REQUIMTE, Departamento de Toxicologia, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4099-030 Porto, Portugal. ricardinis@ff.up.pt <ricardinis@ff.up.pt>
Duarte
J A
JA
Remião
F
F
Sánchez-Navarro
A
A
Bastos
M L
ML
Carvalho
Félix
F
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006540:Herbicides / Q000493:pharmacokinetics / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D009929:Organ Size / Q000187:drug effects; D010269:Paraquat / Q000493:pharmacokinetics / Q000633:toxicity*; D009195:Peroxidase / Q000378:metabolism; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure
D000893:Anti-Inflammatory Agents; D006540:Herbicides; D003907:Dexamethasone; D009195:Peroxidase; D000118:Acetylglucosaminidase; D010269:Paraquat