Repeated subcutaneous administrations of krokodil causes skin necrosis and internal organs toxicity in Wistar rats: putative human implications
Language English Country Great Britain, England Media print
Document type Journal Article
PubMed
28657190
DOI
10.1002/hup.2572
Knihovny.cz E-resources
- Keywords
- desomorphine, in vivo, krokodil, phosphorous, toxicity,
- MeSH
- Injections, Subcutaneous MeSH
- Liver drug effects pathology MeSH
- Codeine administration & dosage analogs & derivatives toxicity MeSH
- Skin Diseases chemically induced pathology MeSH
- Rats MeSH
- Kidney drug effects pathology MeSH
- Humans MeSH
- Necrosis chemically induced pathology MeSH
- Analgesics, Opioid administration & dosage toxicity MeSH
- Oxidative Stress drug effects physiology MeSH
- Lung drug effects pathology MeSH
- Rats, Wistar MeSH
- Heart drug effects MeSH
- Tissue Distribution drug effects physiology MeSH
- Organ Size drug effects physiology MeSH
- Illicit Drugs toxicity MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- desomorphine MeSH Browser
- Codeine MeSH
- Analgesics, Opioid MeSH
- Illicit Drugs MeSH
OBJECTIVE: "Krokodil" is the street name for an impure homemade drug mixture used as a cheap substitute for heroin, containing desomorphine as the main opioid. Abscesses, gangrene, thrombophlebitis, limb ulceration and amputations, jaw osteonecrosis, skin discoloration, ulcers, skin infections, and bleeding are some of the typical reported signs in humans. This study aimed to understand the toxicity of krokodil using Wistar male rats as experimental model. METHODS: Animals were divided into seven groups and exposed subcutaneously to NaCl 0.9% (control), krokodil mixture free of psychotropic substances (blank krokodil), pharmaceutical grade desomorphine 1 mg/kg, and four different concentrations of krokodil (containing 0.125, 0.25, 0.5, and 1 mg/kg of desomorphine) synthesized accordingly to a "domestic" protocol followed by people who inject krokodil (PWIK). Daily injections for five consecutive days were performed, and animals were sacrificed 24 hr after the last administration. Biochemical and histological analysis were carried out. RESULTS: It was shown that the continuous use of krokodil may cause injury at the injection area, with formation of necrotic zones. The biochemical results evidenced alterations on cardiac and renal biomarkers of toxicity, namely, creatine kinase, creatine kinase-MB, and uric acid. Significant alteration in levels of reduced and oxidized glutathione on kidney and heart suggested that oxidative stress may be involved in krokodil-mediated toxicity. Cardiac congestion was the most relevant finding of continuous krokodil administration. CONCLUSIONS: These findings contribute notably to comprehension of the local and systemic toxicological impact of this complex drug mixture on major organs and will hopefully be useful for the development of appropriate treatment strategies towards the human toxicological effects of krokodil.
CIAFEL Faculty of Sport University of Porto Porto Portugal
CVO Addiction Research Centre Utrecht The Netherlands
Department of Analytical Chemistry Chemistry Institute Fluminense Federal University Niterói Brazil
EPSJV Joaquim Venâncio Polytechnic School of Health Oswaldo Cruz Foundation Rio de Janeiro Brazil
Interdisciplinary Center of Marine and Environmental Investigation Porto Portugal
References provided by Crossref.org