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Abstract

Protective Effect of Pyrrolidine Dithiocarbamate to Liver Injury in a Sepsis Model with Cecum Ligation and Perforation – An Animal Study

Introduction: Pyrrolidine dithiocarbamate is a low molecular thiol antioxidant and is a strong inhibitor of nuclear factor kappa B activation. Recent animal studies have shown a delaying effect of intraperitoneal sepsis on healing after colon anastomosis. Our aim in this study is to use pyrrolidine dithiocarbamate in sepsis treatment to research the place of nuclear factor kappa B inhibition in preventing tissue injury and organ function disorders and the effect on organ failure caused by clinical worsening of sepsis.

Materials and methods: Our study was completed on a total of 28 rats in Istanbul University Faculty of Medicine Hospital. In our study subjects were grouped as control (n=4) liver subjects, “Group A” (n=4) (sham group), “Group B” (n=8) (Sepsis group) (laparotomy and cecal mobilization), “Group C” (n=8) Pyrrolidine dithiocarbamate subjects and “Group D” (n=8) sepsis+ Pyrrolidine dithiocarbamate subjects. Apart from the sham group (control group) rats had the polymicrobial sepsis model described in the literature of cecum ligation and perforation used to induce sepsis. Group A (sham group, n=8) had mini laparatomy performed after anaesthesia and then the abdomen was closed without cecum ligation and perforation. Group B (sepsis group, n=8) had the cecum isolated with mini laparotomy, sepsis was induced with the cecum ligation and perforation method and then the abdomen was closed. Group C (Pyrrolidine dithiocarbamate, n=8) had 100 mg/kg/day Pyrrolidine dithiocarbamate administered by gavage 15 minutes before and 12 hours after mini laparotomy procedure. Group D (sepsis+Pyrrolidine dithiocarbamate, n=8) had pyrrolidine dithiocarbamate administed by gavage 15 minutes before and 12 hours after cecum ligation and perforation to induce sepsis.

Results: When mortality in the groups is assessed, as there was no procedure performed on the sham group (performed cecum ligation and perforation or antioxidant administered) no rat died and all 8 rats were sacrificed for histopathological and immunohistochemical assessment. In the Group B of the 7 rats that died, 5 died from 24-36 hours, and 2 were exitus before 48 hours. In Group D (sepsis+ Pyrrolidine dithiocarbamate) 2 were exitus in the first 48 hours with the other 2 exitus on the 5th day and 3 rats were alive on the 10th day. In Group C (sham +Pyrrolidine dithiocarbamate) 1 rat was exitus in the first 72 hours, while the remaining 6 were still alive on the 10th day. The livers of the cases were investigated for morphology, p65 and inductible nitic oxide synthase activity after hematoxylin-eosin and immunohistochemical staining. The results were statistically assessed.

Conclusion: In these results, pyrrolidine dithiocarbamate appears to be an appropriate medication with potential efficacy for sepsis and septic shock treatment. As the results of clinical studies of antioxidants used for sepsis treatment are still controversial, there is a need for broader and longer duration studies.


Author(s):

Abdülcelil Gezmis, Bedih Balkan and Abdulkadir Yektas



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