Studies on the haemotoxicity of chloramphenicol succinate in the Dunkin Hartley guinea pig

Abstract

Summary. In man, chloramphenicol (CAP), induces two major haemotoxic effects. First, a reversible, dose-related reticulocytopenia and anaemia developing during treatment. Second, a non-dose-related aplastic anaemia (AA), developing weeks after treatment, is often irreversible and fatal. In previous studies, we developed a mouse model of the reversible reticulocytopenia/ anaemia using CAP succinate (CAPS); attempts to induce AA in the mouse with CAPS were unsuccessful; in the rat, CAPS induced only minimal haemotoxicity. We therefore wished to investigate haematological changes caused by CAPS in a third rodent, particularly in relation to the induction of significant`late stage' bone marrow depression (AA). Female guinea pigs were gavaged with CAPS in three experiments. In a dose ranging study, CAPS (at 2500 and 3500 mg/kg) was administered daily for 9 days, and blood examined at 1 day post dosing. CAPS induced increased erythrocyte values (an apparent haemoconcentration effect), and reduced reticulocytes and femoral marrow nucleated cell counts (FNCC). In a second experiment, CAPS was given at 333, 666 and 1000 mg/kg (13 days); haematological changes were compared with results from the initial study, with evidence of dose-related effects. In a final experiment, CAPS was administered (825 mg/ kg, 16 days) and blood studied at 1, 12, 28 and 63 days post dosing. At day 1, erythrocyte values were decreased (NS), and reticulocytes and FNCC were reduced; the marrow was hypocellular with erythroid depletion. At 12 and 28 days, values returned towards the normal range. At 63 days, parameters were normal. Thus, CAPS (825 mg/kg for 16 days) induced changes comparable to the reversible bone marrow depression seen in man; but there was no evidence of`late stage' (i.e. at 63 days) marrow depression, as would be seen in a developing or overt marrow aplasia (AA). The guinea pig (like the mouse) is a model for the early events, but is not a good model for CAPinduced AA in man.

Animal Models for Acquired Bone Marrow Failure Syndromes

“…29 More recently, a series of studies failed to produce a chronic aplastic anemia mouse model by using chloramphenicol succinate. [30][31][32][33][34][35] Administration of chloramphenicol succinate at 800 mg/kg to 2000 mg/kg for 7 days to CD1 mice, 31 2000 mg/kg/day for 17 days to BALB/c mice, 32 2000 mg/kg/day to 4000 mg/kg/day for 19 days to Wistar Hanover rats, 31 and 2500 mg/kg/day to 3500 mg/kg/day for 9 days in guinea pigs 35 all induced reversible anemia, but not irreversible aplastic anemia. In these animals, there were usually dose-related reductions in reticulocytes, erythrocytes, hematocrit, hemoglobin, CFU-erythroid, and CFU-GM, but these hematological parameters tend to return to normal without intervention.…”

“…In these animals, there were usually dose-related reductions in reticulocytes, erythrocytes, hematocrit, hemoglobin, CFU-erythroid, and CFU-GM, but these hematological parameters tend to return to normal without intervention. [30][31][32][33][34][35] A significant difference between strains was observed in response to chloramphenicol succinate toxicity. Inbred C3H/He, CBA/Ca, BALB/c, and B6 mice were demonstrated to be much more susceptible to chloramphenicol succinate toxicity than outbred CD1 mice.…”

Targeting Antibacterial Agents by Using Drug-Carrying Filamentous Bacteriophages

“…This leads to the third feature-reintroduction of nonselective toxic substances into active duty as drug candidates in the battle against drug-resistant bacteria. We demonstrate these principles by using the bacteriostatic nonpotent antibiotic chloramphenicol (which has a known toxicity to blood cells [42]) as a model drug. Targeting is demonstrated by using two different targeting moieties: (i) displayed targetspecific peptides that are displayed on the major coat protein of the phage and (ii) immunoglobulin G (IgG) antibodies linked to the phages via an IgG-binding ZZ domain that is displayed on the minor coat protein of the phage.…”

Chromosomal Disturbances during Mitotic Activity of Root Tip Cells in Allium by Certain Commonly Used Antibiotics

“…The normal mitotic (Interphase, Prophase, Metaphase, Anaphase, Telophase and Cytokinensis) images Figure 1-6, interphase (binucleate cells, interphase nucleoli, nuclear chromatin and interphase chromatin) abnormalities Figure 7-10, prophase (interlaced chromatin, micronucleus, intermingled, looplike structure, sticky, ring like structure, disturbed sticky) abnormalities Figure 11-16, metaphase (disturbed, micronuclei, sticky, interlaced, sticky equatorial and intermingled) abnormalities (17)(18)(19)(20)(21)(22)(23)(24), anaphase (fragments, bridges, sticky, loose chromatids, chromatids dissolved type, bipolar at both poles, bipolar at one pole, multipolar, intermingled and dysjunct) abnormalities , telophase (telocytokinesis, telocytomixis, telocytonucleomixix) abnormalities (53)(54)(55), cytokinesis (cell notch, cell plate) abnormalities (56)(57) and other (nuclear membrane granules, nucleomixis) abnormalities (58-59) were recorded.…”

“…Also, BMD had been reported in household animals. 24 Ciprofloxacin (CFX) is a fluroquinolone antibiotic drug with broad spectrum antibacterial and effective microbicidal activity. The antibacterial drug ciprofloxacin was evaluated for its genotoxic effects.…”