Effect of tetracyclines and UV light on oxygen consumption by human leukocytes

Abstract

When polymorphonuclear leukocytes were stimulated with zymosan, a sharp rise in oxygen consumption was observed. In the presence of doxycycline, we observed a further increase in oxygen consumption when the phagocytosing cells were exposed to UV light. When the light was turned off, oxygen consumption of the cells almost ceased, indicating photodamage to polymorphonuclear leukocytes during irradiation. Irradiation of the polymorphonuclear leukocytes for 20 min in the presence of doxycycline (10 ,Ig/ml) before phagocytosis completely abolished the rise in oxygen consumption initiated by zymosan. Demethylchlortetracycline and light exposure also caused a marked reduction of polymorphonuclear leukocyte oxygen consumption, whereas oxytetracycline, lymecycline, chlortetracycline, and minocycline had only a slight or no photosensitizing effect. The photodamage induced by doxycycline and demethylchlortetracycline was inhibited by azide and enhanced in deuterium oxide. This was in accordance with singlet oxygen-mediated damage.Polymorphonuclear leukocytes (PMNLs) are cornerstones of host defenses against infections. During phagocytosis and intracellular killing of bacteria by PMNLs, oxygen consumption takes place (16,20), and toxic oxygen radicals essential for the killing of phagocytosed bacteria (22, 27) are generated (1, 5). Several drugs, including tetracyclines, have been shown to influence these functions. However, studies with tetracyclines are inconsistent. High concentrations of chlortetracycline, doxycycline, and minocycline have been reported to markedly inhibit in vitro PMNL functions, whereas similar effects have not been demonstrated for oxytetracycline or tetracycline hydrochloride (15,18,19). We have previously shown that low concentrations (<10 pug/ml) of tetracyclines had no influence on in vitro PMNL functions, whereas high concentrations inhibited these functions. This inhibition was abolished when increasing concentrations of divalent cations were added to the medium (8, 9).Besides the chelating effect, tetracyclines may also influence PMNL function by other mechanisms. It is well known that these drugs can cause skin lesions in patients exposed to the sun (4,7,13,14,21,28), and we have recently shown that doxycycline can induce photodamage to PMNLs (24). In the present study, we examined the effect of six tetracyclines on PMNL oxygen consumption in the presence of UV light. In addition, the mechanism of tetracycline-induced photodamage was studied.MATERIALS AND METHODS Preparation of cells. Ten parts heparinized (18 U/ml) blood mixed with three parts dextran solution (60 mg/ml; Pharmacia, Uppsala, Sweden) were sedimented at room temperature. After centrifugation of the supernatant (500 x g, 5 min) the erythrocytes were lysed with ammonium chloride (0.15 M; pH 7.4), and the leukocytes (of which 60 to 80% were PMNLs) were washed twice in phosphate-buffered saline. The leukocytes were suspended in phosphate-buffered saline (pH 7.3) to a concentration of 107 cells per ml. Tetracycline was added to the ...

Oxytetracycline induces DNA damage and epigenetic changes: a possible risk for human and animal health?

“…Despite scientific literature that has been suggesting the potential toxicity of OTC ( Czeizel & Rockenbauer, 2000 ; Glette et al, 1984 ; Potts et al, 1983 ; Van den Bogert & Kroon, 1982 ; Myers, Farrell & Henderson, 1995 ), the mechanisms of the toxic effect of such drug is still poor understood.…”

“…Several studies have investigated the potential toxicity of OTC ranging from teratogenic effects during pregnancy ( Czeizel & Rockenbauer, 2000 ) to some effect on immune system ( Glette et al, 1984 ; Potts et al, 1983 ; Van den Bogert & Kroon, 1982 ; Myers, Farrell & Henderson, 1995 ; Di Cerbo et al, 2016 ). Moreover, scientific literature suggested that the drug is able to inhibit or reduce catalase ( Chi, Liu & Zhang, 2010 ) and affects avian cartilage degradation ( Peters et al, 2002 ).…”

Spectral distribution of the luminescence generated during oxidation of doxycycline

“…It has been found that when polyphenols and aminophenols were incubated with deoxyguanosine or guanine base in the presence of H 2 O 2 and Fe 3+ , the hydroxylation of the bases was observed 17 and oxygen radicals were postulated to be responsible for the damages. It has also been reported that high concentration of doxycycline inhibited in vitro kills bacteria by polymorphonuclear leucocytes 18 . Downloaded by [University North Carolina -Chapel Hill] at 11:12 01 December 2014…”

Effect of hyperbaric oxygen treatment on immunological parameters in multiple sclerosis

“…The purity of the cell suspension was 97.3k4.7'70 for the granulocytes and 100% for the mononuclear cells, which included 6-7 070 monocytes . Oxygen consumption was quantitated as described by Glette et a1 (14).…”