Does dexmedetomidine prevent colistin nephrotoxicity? <span class="so-article-trans-title" dir="auto"> Translated title: Dexmedetomidina impede a nefrotoxicidade da colistina? </span>

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Abstract

Background

In this study, we aimed to investigate the effect of dexmedetomidine on colistin nephrotoxicity in rats.

Methods

Thirty-two Wistar albino rats were allocated into four groups. Intraperitoneal (ip) saline at 1 mL.kg ⁻¹ was administered to the control group and 10 mg.kg ⁻¹ ip colistin was given to the colistin group. In the DEX10 group 10 mcg.kg ⁻¹ dexmedetomidine ip was given 20 min before the injection of 10 mg.kg ⁻¹ ip colistin. In the DEX20 group ip 20 mcg.kg ⁻¹ dexmedetomidine was injected 20 min before the administration of 10 mg.kg ⁻¹ ip colistin. These treatments were continued twice a day for seven days. Samples were taken on the eighth day. BUN, Cr, KIM-1, TAS, and TOS were examined in blood samples and caspase-3 was examined in kidney tissue samples.

Results

The values for BUN, Cr and TOS were significantly higher in the colistin group than in the control group. BUN, Cr and TOS changes in the DEX10 and DEX20 groups were not significant compared with the control group but they were significantly lower compared with the colistin group. TAS values in the DEX10 group were significantly lower than in the control group. Apoptotic activity was significantly higher in the colistin group compared with the control group, but there was no significant difference in terms of caspase-3 staining activity when DEX10 and DEX20 groups were compared with the control group.

Conclusion

Oxidative damage and apoptosis played roles in colistin nephrotoxicity, and colistin nephrotoxicity could be prevented by treatment with dexmedetomidine.

Resumo

Justificativa

Neste estudo, buscamos investigar o efeito da dexmedetomidina sobre a nefrotoxicidade da colistina em ratos.

Métodos

Trinta e dois ratos Wistar albinos foram alocados em quatro grupos: o grupo controle recebeu 1 mL.kg ⁻¹ de solução salina intraperitoneal (ip); o grupo colistina recebeu 10 mg.kg ⁻¹ de colistina ip; o grupo DEX10 recebeu 10 mcg.kg ⁻¹de dexmedetomidina ip 20 minutos antes da injeção de 10 mg.kg ⁻¹ de colistina ip; o grupo DEX20 recebeu 20 mcg.kg ⁻¹ de dexmedetomidina ip 20 minutos antes da administração de 10 mg.kg ⁻¹ de colistina ip. Estes tratamentos foram continuados duas vezes ao dia durante sete dias. As amostras foram colhidas no oitavo dia. BUN, Cr, KIM-1, TAS e TOS foram examinados nas amostras de sangue e caspase-3 foi examinada nas amostras de tecido renal.

Resultados

Os valores de BUN, Cr e TOS foram significativamente maiores no grupo colistina que no grupo controle. As alterações em BUN, Cr e TOS nos grupos DEX10 e DEX20 não foram significativas em comparação com o grupo controle, mas foram significativamente menores em comparação com o grupo colistina. Os valores de TAS no grupo DEX10 foram significativamente menores que no grupo controle. A atividade apoptótica foi significativamente maior no grupo colistina em comparação com o grupo controle, mas não houve diferença significativa em termos de atividade na coloração da caspase-3 quando os grupos DEX10 e DEX20 foram comparados com o grupo controle.

Conclusão

O dano oxidativo e a apoptose desempenharam papéis na nefrotoxicidade da colistina, e a nefrotoxicidade de colistina pode ser prevenida pelo tratamento com dexmedetomidina.

Related collections

Most cited references 22

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Dexmedetomidine: a novel sedative-analgesic agent.

R Gertler, H Brown, D H Mitchell … (2001)

Since the first report of clonidine, an alpha2-adrenoceptor agonist, the indications for this class of drugs have continued to expand. In December 1999, dexmedetomidine was approved as the most recent agent in this group and was introduced into clinical practice as a short-term sedative (<24 hours). Alpha2-adrenoceptor agonists have several beneficial actions during the perioperative period. They decrease sympathetic tone, with attenuation of the neuroendocrine and hemodynamic responses to anesthesia and surgery; reduce anesthetic and opioid requirements; and cause sedation and analgesia. They allow psychomotoric function to be preserved while letting the patient rest comfortably. With this combination of effects, alpha2-adrenoceptor agonists may offer benefits in the prophylaxis and adjuvant treatment of perioperative myocardial ischemia. Furthermore, their role in pain management and regional anesthesia is expanding. Side effects consist of mild to moderate cardiovascular depression, with slight decreases in blood pressure and heart rate. The development of new, more selective alpha2-adrenoceptor agonists with improved side effect profiles may provide a new concept for the administration of perioperative anesthesia and analgesia. This review aims to give background information to improve understanding of the properties and applications of the novel alpha2-adrenoceptor agonist, dexmedetomidine.

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alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role.

Sohrab Z. Khan, Jonathan Jones, Mhairi C. Ferguson (1999)

Clonidine has proved to be a clinically useful adjunct in clinical anaesthetic practice as well as in chronic pain therapy because it has both anaesthetic and analgesic-sparing activity. The more selective alpha-2 adrenoceptor agonists, dexmedetomidine and mivazerol, may also have a role in providing haemodynamic stability in patients who are at risk of peri-operative ischaemia. The side-effects of hypotension and bradycardia have limited the routine use of alpha-2 adrenoceptor agonists. Investigations into the molecular pharmacology of alpha-2 adrenoceptors have elucidated their role in the control of wakefulness, blood pressure and antinociception. We discuss the pharmacology of alpha-2 adrenoceptors and their therapeutic role in this review. The alpha-2 adrenoceptor agonists are agonists at imidazoline receptors which are involved in central blood pressure control. Selective imidazoline agonists are now available for clinical use as antihypertensive agents and their pharmacology is discussed.