To investigate the in vitro effects of gentamicin sulfate, vancomycin hydrochloride, sodium cefazolin and ceftriaxone on glucose 6-phosphate dehydrogenase enzyme (G6PD) purified from sheep lenses.
Methods
G6PD was purified from sheep lenses with a yield of 66.8% and a specific activity of 7.8 U/mg proteins, and 10,400-fold using ammonium sulfate fractionation and 2′,5′-ADP Sepharose 4B affinity gel. The enzyme activity was determined by Beutler's method.
Results
Gentamicin sulfate and vancomycin hydrochloride strongly inhibited the enzyme in vitro. The concentrations causing 50% inhibition (IC50) were 15.34, and 8.0 mM, respectively. Conversely, cefazolin sodium strongly activated this enzyme, and ceftriaxone caused milder activation.
Conclusions
If a patient with G6PD deficiency requires gentamicin sulfate or vancomycin hydrochloride, routine ophthalmic did not inhibit this enzyme. Postmortem studies are now needed to investigate the activity of G6PD and how it is affected by these antibiotics.
GlockG.E.McLeanP.. Levels of enzymes of the direct oxidative pathway of carbohydrate metabolism in mammalian tissues and tumors.Biochem J1954; 56: 171–5.
4.
BuonsignoreA.De FloraA.. Regulatory properties of G6PD.Curr Top Cell Regul1972; 6, 21.
5.
OuwerkerkR.DamenP.De HaanK.StaalG.E.J.RijksenG.. Hexose monophosphate shunt activity in erythrocytes related to cell age.Eur J Haematol1989; 43: 441–7.
6.
NinfaliP.PalmaF.. Comparative study on glucose 6-phosphate dehydrogenase from rabbit tissues.J Exp Zool1990; 254: 6–12.
7.
OgawaK.SoltD.B. and FarberE.. Phenotypic diversity as an early property of putative preneoplastic hepatocyte populations in liver carcinogenesis.Cancer Res1980; 40: 725–33.
8.
ShannonW.N.GoverS.LamM.S.AdamsM.J.. Human glucose 6-phosphate dehydrogenase: the crystal structure reveals a structural NADP+ molecule and provides insights into enzyme deficiency.Structure2000; 8: 293–303.
9.
HockwinO.OhrlofC.. Enzymes from normal, aging and cataractous lenses. In: BloemendalH., ed. Molecular and cellular biology of the lens.New York: Wiley, 1981; 367–413.
10.
HardingJ.J.CrabbeM.J.C.. The lens: development, proteins, metabolism and cataract. In: Davson, ed. The Eye.London: Academic Press1984; 207–492.
11.
ChylackL.T.ChengH.M.. Sugar metabolism in the crystalline lens.Surv Ophthalmol1978; 23: 26–34.
12.
PirieA.van HeyningenR.BoagJ.W.. Changes in lens during the formation of X-ray cataract in rabbits.Biochem J1953; 54: 682–8.
13.
DovratA.GershonD.. Rat lens superoxide dismutase and glucose 6-phosphate dehydrogenase; studies on catalytic activity and the fate of enzyme antigen as a function of age.Exp Eye Res1981; 33: 651–61.
14.
RawalU.M.RaoG.N.. Effect of galactose on the metabolism of the rat lens in vitro.Indian J Exp Biol1978; 16: 499–501.
15.
RawalU.M.GandhiD.N.. Activities of glucose 6-phosphate dehydrogenase and sorbitol dehydrogenase in alloxan-induced cataract. An experimental study.Indian J Pharmacol1984; 16: 99–101.
16.
MeloniT.CartaF.ForteleoniG.CartaA.EnaF.MeloniG.F.. Glucose 6-phosphate dehydrogenase deficiency and patients in Northern Sardinia.Am J Ophthalmol1990; 110: 661–4.
17.
YüreğirG.T.AksoyK.ArpaciA.ÜnlükurtÍTuliA.. Studies on red cell glucose-6-phosphate dehydrogenase: evaluation of reference values.Ann Clin Biochem1994; 31: 50–5.
18.
JaffeN.S.HorwitzJ.. Textbook of ophthalmology (PodosM.S. and YanoffM. eds), London: Times Mirror International Publishers Limited1995; 3: 7.1–7.9.
19.
OrzalesiN.FossarelloM.SorcinelliR.SchlichU.. The relationship between glucose 6-phosphate dehydrogenase deficiency and cataracts in Sardinia. An epidemiological and biochemical study.Doc Ophthalmol1984; 57: 187.
20.
ÇiftçiM.KüfrevioğluÖIGündoğduM.ÖzmenI.. Effects of some antibiotics on enzyme activity of glucose 6-phosphate dehydrogenase from human erythrocytes.Pharmacol Res2000; 41: 109–13.
21.
RichardsF.McCallD.CoxC.. Gentamicin treatment in staphylcoccal infections.JAMA1971; 215: 1297–300.
22.
FurgiueleF.P.. Penetration of gentamicin into the aqueous humor of human eyes.Am J Ophthalmol1970; 69: 481–3.
23.
Meredith Tai AguilarH.E.ShaarawyA.Vancomycin hydrochloride levels in the vitreous cavity after intravenous administration.Am J Ophthalmol1995; 119: 774–8.
24.
GordonV.J.. Vancomycin hydrochloride prophylaxis and emerging resistance: are the ophthalmologists the villains or the heroes?Am J Ophthalmol2001; 131: 371–6.
25.
MoelleringR.C.SwartzM.N.. The newer cephalosporins.N Engl J Med1976; 294: 24.
26.
PittalisS.MontemurosF.M.TavazziD.ForelliG.. Rapid isolation of glucose 6-phosphate dehydrogenase from human erythrocytes by combined affinity and anion-exchange chromatography for biochemical characterization of variants.J Chromatogr1992; 573: 29–34.
27.
NinfaliP.OrsenigoT.BarocianiL.RapaS.. Rapid purification of glucose 6-phosphate dehydrogenase from mammal's erythrocytes.Preparative Biochemistry1990; 20: 297–309.
BradfordM.M.. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal Biochem1976; 72: 248–51.
30.
LaemmLiD.K.. Cleavage of structural proteins during assembly of the head of bacteriophage T4.Nature1970; 227: 680–3.
ChristensenG.M.OlsonD.RiedelB.. Chemical effects on the activity of eight enzymes: A review and discussion relevant to environmental monitoring.Environ Res1982; 29: 247–55.
33.
ÇiftçiM.ÖzmenI.BüyükokuroğluM.E.PençeS.KüfrevioğluÖI. Effects of metamizol and magnesium sulfate on enzyme activity of glucose 6-phosphate dehydrogenase from human erythrocytes in vitro and rat erythrocytes in vivo.Clin Biochem2001; 34: 297–302.
34.
BeydemirŞÇiftçiM.ÖzmenBüyükokuroğluM.E.ÖzdemirH.KüfreviogluÖ. Effects of some medical drugs on enzyme activities of carbonic anhydrase from human erythrocytes in vitro and from rat erythrocytes in vivo.Pharmacol Res2000; 42: 187–91.
35.
BelgeE.YüregirG.TuncerI.. The effect of halothane on the enzymatic activity of mouse liver and erythrocyte glucose 6-phosphate dehydrogenase.Tr J Med Sci2000; 30: 219–22.
36.
OrzalesiN.SorcinelliR.GuisoG.. Increased incidence of cataracts in male subjects deficient in glucose 6-phosphate dehydrogenase.Arch Ophthalmol1981; 99: 69–70.
37.
PannacciulliI.TizianelloA.SalvidioE.. L'attività della G6PD e 6PGD dei leucociti, delle piastrine, delle cellule midollari, spleniche, epatiche e di tessuto gastri-co in sogetti con eritroenzimopenia familiare.Boll Soc Ital Biol Sper1966; 42: 1552–7.
38.
ZinkhamW.H.. A deficiency of glucose 6-phosphate dehydrogenase activity in lens from individuals with primaquine-sensitive erythrocytes.Bull Johns Hopkins Hosp1961; 109: 206–10.
39.
WestringD.PisciottaA.V.. Anemia, cataracts and seizures in a patient with glucose 6-phosphate dehydrogenase deficiency.Arch Intern Med1966; 118: 385–90.
40.
OrzalesiN.SorcinelliR.BinaghiF.. Glucose 6-phosphate dehydrogenase in cataracts of subjects suffering from favism.Ophthalmol Res1976; 8: 192–4.
41.
GlässerD., cited by OhrloffC.BousF.HockwinO.. Competition of glucose 6-phosphate dehydrogenase enzyme of bovine lenses.Doc Ophthalmol1976; 8: 177–83.
YüregirG.VarinliI.DonmaO.. Glucose 6-phosphate dehydrogenase deficiency both in red cells and lenses of the normal and cataractous native population of Çukurova, in the Southern part of Turkey.Ophthalmic Res1989; 21: 155–7.
44.
RybczynskaM.FeoC.MardenM.PoyartC.. Abnormal rheological response of erythrocytes caused by nitroimidazoles and hyperthermia.Int Hyperthermia1993; 9: 313–23.
45.
BartoszG.GaczynskaM.RetelewskaW.GrzelinskaE.RosinJ.. Hyperthermia, unlike ionizing radiation and chemical oxidative stress, does not stimulate proteolysis in erythrocytes.Int J Biochem1990; 1: 25–30.
46.
Ben-MenachemE.KyllermanM.MarklundS.. Superoxide dismutase and glutathione peroxidase function in progressive myclonus epilepsies.Epilepsy Res2000; 40: 33–9.
47.
SloanS.H.PettitT.H.LitwackK.D.. Gentamicin penetration in the aqueous humor of eyes with corneal ulcers.Am J Ophthalmol1972; 73: 750–3.
48.
O'BrienT.P.. Bacterial keratitis study research group: Efficacy of floxacin vs. cefazolin and tobramycin for bacterial keratitis.Arch Ophthalmol1995; 113: 1257–65.
49.
JonesD.B.. Emerging antibiotic resistance: real and relative.Arch Ophthalmol1996; 114: 91–2.
