Some toxicological investigations of rifampicin
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1
Trakia University, Department of Pharmacology, Physiology of Animals and Chemistry, Bulgaria
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2
Biovet, Bulgaria
Introduction. Rifampicin is a bactericidal antibiotic of the Anzamycin,s group. It is a semisynthetic compound derived from Streptomyces mediterranei. Rifampicin is semisynthetic broad-spectrum antibiotic highly active against Mycobacterium tuberculosis. It is active against Gram-positive microorganisms, as well as against some Gram-negative microorganisms. The purpose of the present study was to determine it acute and chronic toxicity.
Materials and methods. The acute toxicity was determined in male and female mice “ICR” weighing 18-22 g male and female Wistar rats weighing 120-140 g. All animals were housed in air-conditioned quarters (20±1°C; 55-60 % humidity) and received a standard diet. Tap water was allowed ad libitum. Tubocin was dissolved with re-distilled water as a 10 % solution and administered p.o., i.p., i.m. and i.v. injection. The observation period was 14 days. Necropsies were performed on animals dying during the study and on those killed at the end of trial. The LD50 were calculated with computer program ToxStat using Behtentz-Schlosser method. All animals were observed in physical appearance and behavior for 14 days prior to necropsy. Chronic (90-days) toxicity in rats. For this examination the drug was received daily via oral route of administration. The rats (Vistar) were divided into 4 groups (24 males and 24 females of each). They received Tubocin or the vehicle every day for 3 months. The antibiotic was administered in a dose 200, 400 and 800 mg/kg of body weight. The hematological and biochemical examinations of blood were performed on all rats before starting the treatment and at 15, 30, 45, 60, 75 and 90 days later on 6 animals randomly chosen from each group (3 males and 3 females). Complete necropsy examinations were performed on all animals at the end of chronic toxicity.
Results. Acute toxicity in rats and mice. The results of LD50 values were calculated and reported in Table 1.
Chronic toxicity of rifampicin. During the period of the 90-day chronic toxicity were not registered lethal cases or changes in the general condition or behaviour.There were not registered statistically significant differences in the body weight.The haematological investigations determined comparatively lower values of the haemoglobin in the blood of the rats from groups III and IV at the 90th day compared to the controls, with a presence of statistically significant differences. At the 90th day from the beginning of the treatment, the percentage of the segmented heterofils in the IVthgroup was statistically significant higher than the one for the control group.With the increase of the dose of rifampicin the percentage of the eosinophils increases. The differences were statistically significant for the II and IIIrd groups.The percentage of the lymphocytes was significantly lower for the IVth group compared to the values for the control group. At the end of the rehabilitation period the fore mentioned statistically significant differences remained for the eosinophils and the lymphocytes for the rats from III and IV groups.With the increase of the dosage of the antibiotic, the values of the transaminase ASAT raised, without the presence of a statistically significant difference.The level of blood glucose lowered with the increase of the dose, without the presence of a significant difference. After rehabilitation period the levels of blood glucose did not raised and remained lower, than the values for the control group. The values for the IVth group were statistically significant lower.The values of the blood cholesterol raised for group III and for group IV, with the presence of statistically significant differences. At the end of the rehabilitation period there were no statistically significant differences.At the end of the 90-days period of treatment the pathoanatomical investigations determined evident changes in the IIIrd and IVth group localised in the digestive system – liver, stomach and duodenum. The observed structural changes were not determined after a 30 day long rehabilitation period.
Keywords:
Toxicity,
rifampicin,
pharmacokinetics
Conference:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010, Thessaloniki, Greece, 1 Oct - 5 Oct, 2010.
Presentation Type:
Poster
Topic:
Xenobiotic toxicity
Citation:
Dimitrova
DJ,
Dimitrov
DS and
Dimitrova
AK
(2010). Some toxicological investigations of rifampicin.
Front. Pharmacol.
Conference Abstract:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010.
doi: 10.3389/conf.fphar.2010.60.00114
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Received:
28 Oct 2010;
Published Online:
04 Nov 2010.
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Correspondence:
Dr. D J Dimitrova, Trakia University, Department of Pharmacology, Physiology of Animals and Chemistry, Stara Zagora, Bulgaria, dj.dimitrova.56@gmail.com