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Single high dose dexamethasone treatment decreases the pathological score and increases the survival rate of paraquat-intoxicated rats.
Toxicology. 2006 Oct 03; 227(1-2):73-85.T

Abstract

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.

Authors+Show Affiliations

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>No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16956706

Citation

Dinis-Oliveira, R J., et al. "Single High Dose Dexamethasone Treatment Decreases the Pathological Score and Increases the Survival Rate of Paraquat-intoxicated Rats." Toxicology, vol. 227, no. 1-2, 2006, pp. 73-85.
Dinis-Oliveira RJ, Duarte JA, Remião F, et al. Single high dose dexamethasone treatment decreases the pathological score and increases the survival rate of paraquat-intoxicated rats. Toxicology. 2006;227(1-2):73-85.
Dinis-Oliveira, R. J., Duarte, J. A., Remião, F., Sánchez-Navarro, A., Bastos, M. L., & Carvalho, F. (2006). Single high dose dexamethasone treatment decreases the pathological score and increases the survival rate of paraquat-intoxicated rats. Toxicology, 227(1-2), 73-85.
Dinis-Oliveira RJ, et al. Single High Dose Dexamethasone Treatment Decreases the Pathological Score and Increases the Survival Rate of Paraquat-intoxicated Rats. Toxicology. 2006 Oct 3;227(1-2):73-85. PubMed PMID: 16956706.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Single high dose dexamethasone treatment decreases the pathological score and increases the survival rate of paraquat-intoxicated rats. AU - Dinis-Oliveira,R J, AU - Duarte,J A, AU - Remião,F, AU - Sánchez-Navarro,A, AU - Bastos,M L, AU - Carvalho,Félix, Y1 - 2006/08/03/ PY - 2006/06/20/received PY - 2006/07/13/revised PY - 2006/07/14/accepted PY - 2006/9/8/pubmed PY - 2006/12/9/medline PY - 2006/9/8/entrez SP - 73 EP - 85 JF - Toxicology JO - Toxicology VL - 227 IS - 1-2 N2 - 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. SN - 0300-483X UR - https://www.unboundmedicine.com/medline/citation/16956706/Single_high_dose_dexamethasone_treatment_decreases_the_pathological_score_and_increases_the_survival_rate_of_paraquat_intoxicated_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(06)00473-2 DB - PRIME DP - Unbound Medicine ER -