Two types of chloramphenicol-induced toxicity in humans have been widely discussed. The first is a frequently occurring, dose-related, bone-marrow depression that develops during treatment with chloramphenicol. The condition is seen as a mild anaemia, with decreased haemoglobin concentrations and reticulocytopenia, with the bone marrow showing reduced erythroid precursors, increased myeloid : erythroid cell ratio and vacuolation of erythroid cells. The patient returns to normal after drug withdrawal. Inhibition of protein synthesis in bone-marrow cells has been proposed as the mechanism of these effects (Kucers et al., 1997). The second is a severe, non-dose-related aplastic anaemia, which is irreversible. Aplastic anaemia is evident as severe pancytopenia in peripheral blood, with an acellular or hypocellular bone marrow. This might also result in leukaemia in humans (Dollery, 1999; Turton et al., 2002a).
Preparation Methods : benzaldehyde as raw material, potassium nitrate, nitrite, nitrate or sulfate in the presence of nitrification, can generate between nitrobenzaldehyde, and the yield is about 80%, 60% and 75%.
Inhibition of protein synthesis in the mitochondria of bone-marrow cells has been considered as a mechanism by which bone-marrow depression is induced by chloramphenicol. The underlying cytotoxicity may be caused by the similarity between mitochondrial ribosomes and bacterial ribosomes, both of which are 70S. Thus chloramphenicol can also inhibit mitochondrial protein synthesis in mammalian cells, particularly in erythropoietic cells, which appear to be sensitive to the drug (Sande & Mandell, 1993; Kucers et al., 1997). It was reasoned that the inhibition of mitochondrial protein synthesis suppressed the division of mitochondria and resulted in the formation of megamitochondria. Investigation of the toxicity caused by chloramphenicol in mouse hepatic cells in vivo, however, showed that antioxidants prevented the formation of megamitochondria (Matsuhashi et al., 1996). The role of antioxidants in reducing the cytotoxic effects of chloramphenicol was also reported to occur in vitro in a study using a monkey kidney-derived cell line and haematopoietic progenitor cells from human neonatal cord blood. Also, in cells in culture, the cytotoxic effects of chloramphenicol on apoptosis and suppression of progenitor cell growth were not pronounced when cells were co-cultured with antioxidants such as mercaptoethylamine or vitamin C (Holt et al., 1997). Both studies suggested that toxicity caused by chloramphenicol relates intimately to oxidative stress, with a possible link between a metabolic event—the production of free radicals—and bone marrow suppression.
Chloramphenicol-aldehyde as a metabolic product of chloramphenicol was identified in a study in four children with major infections treated with chloramphenicol at a dose of 50 mg/kg bw per day). The residues in samples of urine collected during the treatment were analysed using HPLC and GC-MS. Results indicated the existence of compounds with characteristics corresponding to the synthesized chloramphenicol-aldehyde derivatives. The author concluded that chloramphenicol-aldehyde, a metabolite that was toxic to bone marrow and previously observed only in rat hepatic tissue, was a new metabolite in humans (Holt, 1995).
In the pharmaceutical industry for the synthesis of calcium iodine Cape, iopanoic acid, tartaric acid Aramine heavy salt, nimodipine, nicardipine, nitrendipine, Niro equal.
Substances added to water, oil, or synthetic drilling muds or other petroleum production fluids to control foaming, corrosion, alkalinity and pH, microbiological growth or hydrate formation, or to improve the operation of processing equipment during the production of oil, gas, and other products or mixtures from beneath the earth’s surface.
Whether antibiotics are produced in soil in detectable amounts by indigenous soil organisms has remained a subject of scientific dispute for several decades. It was only recently demonstrated that an antibiotic could be synthesized in detectable amounts in soil. Using biosensor methods with very low LODs, was found to produce oxytetracycline in untreated soil. However, similar studies have not been carried out for chloramphenicol.
The Food and Drug Administration of the USA has published an environmental assessment of chloramphenicol in the context of a proposal made in March 1985 to withdraw approval of new animal drug applications (NADAs) using chloramphenicoloral solution (Food and Drug Administration, 1985). Further information was obtained from the Hazardous Substances Databank, a database of the National Library of Medicine's TOXNET system (Hazardous Substances Databank, 2003). The information available from these sources (most of the original literature cited was not available for this review) is summarized as follows. The solubility of chloramphenicol in water at 25°C is 2.5 g/l over a wide range of pH. Chloramphenicol is not adsorbed to clay or soil to any significant degree and therefore has very high mobility in soil. Adsorption to sediment and bioconcentration in aquatic organisms should not be important processes. Chloramphenicol is degraded by biological, chemical, and photolytic means and undergoes oxidation, reduction and condensation reactions upon exposure to light in aqueous solution. Photochemical decomposition of chloramphenicol in vitro by ultraviolet-A (UV-A) light leads to the formation of nitrobenzaldehyde (pNB), nitrobenzoic acid (pNBA) and nitrosobenzoic acid (pNOBA); the latter comprises up to 45% by molarity of the starting amount of chloramphenicol (de Vries et al., 1994).
Whether antibiotics are produced in soil in appreciable amounts by indigenous soil organisms has remained a scientific dispute for several decades. Only recently, it has been demonstrated that an antibiotic can be synthesized in detectable amounts in soil. Using biosensor methods with very low LODs, Hansen et al. (2001) have demonstrated the presence of oxytetracycline produced by in untreated soil. However, similar studies with chloramphenicol were not found.
The biosynthetic route of chloramphenicol starts with the general shikimate pathway for assembling aromatic structures. It then branches at chorismic acid to generate amino-phenylalanine, which serves as an advanced precursor of the nitrophenylserinol moiety of chloramphenicol (He et al., 2001; Lewis et al., 2003). 3’--Acetyl-chloramphenicol, which is commonly formed from chloramphenicol by many resistant bacteria, has also been isolated from the antibiotic-producing organism. It has been suggested that it is a protected intermediate in chloramphenicol biosynthesis, implicating acetylation as a self-resistance mechanism in the producing organism (Gross et al., 2002). 3’--Acetyl-chloramphenicol esterase activity was detected in cell-free extracts of strains of other spp. and var. , which produced chloramphenicol (Nakano et al., 1977).
Chloramphenicol was first described as a new antibiotic produced by cultures of an actinomycete isolated from soil by Ehrlich et al. (1947). The soil samples from which the strains were isolated were collected from a mulched field near Caracas, Venezuela (strain ATCC 10712) and from a compost soil on the horticultural farm of the Illinois Agricultural Experiment Station at Urbana (strain ATCC 10595), respectively. It was demonstrated by Ehrlich et al. (1948) that this actinomycete was a new species. The dynamics of the synthesis of chloramphenicol were studied under laboratory conditions by Legator & Gottlieb (1953), who showed that the peak concentration of chloramphenicol in the culture medium was reached hours after the growth peak of the microorganisms. The antibiotic was not accumulated intracellularly. Addition of chloramphenicol to the culture medium inhibited the synthesis of the antibiotic.