The effect of thiamine pyrophosphate on ethambutol-induced ocular toxicity.
BACKGROUND
Ethambutol-induced retinal oxidative damage in patients with tuberculosis is still not being adequately treated. The protective effect of thiamine pyrophosphate against oxidative damage in some tissues has been reported, but no information on the protective effects of thiamine pyrophosphate against ethambutol-induced oxidative retinal damage has been found in the medical literature.


OBJECTIVE
The objective is to investigate whether thiamine pyrophosphate has a protective effect against oxidative retinal damage in rats induced by ethambutol.


METHODS
Experimental animals divided into four groups (n = 10): the healthy group (HG), the ethambutol control group (EMB), thiamine + ethambutol group (Thi-EMB) and thiamine pyrophosphate + ethambutol group (TPP-EMB). The rats in the TPP-EMB and Thi-EMB groups were administered thiamine pyrophosphate and thiamine, respectively, at doses of 20 mg/kg intraperitoneally. Distilled water was administered intraperitoneally to the HG and the EMB groups as a solvent in the same volumes. One hour after drug injection, 30 mg/kg ethambutol was administered via an oral gavage to the TPP-EMB, Thi-EMB and EMB groups. This procedure was repeated once a day for 90 days. At the end of this period, all rats were euthanized under high-dose thiopental sodium anesthesia, and biochemical and histopathological investigations of the retinal tissue were performed.


RESULTS
Malondialdehyde (MDA) and DNA damage product 8-hydroxyguanine levels were significantly lower in the retinal tissue of TPP-EMB and HG groups compared to those of the Thi-EMB and EMB groups, and total glutathione (tGSH) was also found to be higher. In addition, severe retinal tissue vascularization, edema and loss of ganglion cells were observed in the Thi-EMB and EMB groups, whereas histopathological findings for the TPP-EMB group were observed to be close to normal.


CONCLUSIONS
These findings suggest that thiamine pyrophosphate protects retinal tissues from ethambutol-induced oxidative damage, and thiamine does not. This positive effect of thiamine pyrophosphate may be useful in the prevention of ocular toxicity that occurs during ethambutol use.
a Department of Ophthalmology , Erzurum Region Education and Research Hospital , Erzurum , Turkey .
Emine
E
Cinici
b Department of Pharmacology, Faculty of Medicine , Erzincan University , Erzincan-Turkey .
Nihal
N
Cetin
c Department of Ophthalmology , Palandoken State Hospital , Erzurum , Turkey .
Ibrahim
I
Ahiskali
b Department of Pharmacology, Faculty of Medicine , Erzincan University , Erzincan-Turkey .
Bahadir
B
Suleyman
b Department of Pharmacology, Faculty of Medicine , Erzincan University , Erzincan-Turkey .
Durdu
D
Altuner
d Department of Biochemistry, Faculty of Medicine , Yuzuncuyil University , Van , Turkey , and.
Hamit Hakan
HH
Alp
e Department of Pathology , Erzurum Region Education and Research Hospital , Erzurum , Turkey.
Ebru
E
Sener
e Department of Pathology , Erzurum Region Education and Research Hospital , Erzurum , Turkey.
Ilknur
I
Calik
b Department of Pharmacology, Faculty of Medicine , Erzincan University , Erzincan-Turkey .
Halis
H
Suleyman
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000009:adverse effects*; D004249:DNA Damage; D004977:Ethambutol / Q000009:adverse effects*; D005123:Eye / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005128:Eye Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D013831:Thiamine / Q000494:pharmacology / Q000627:therapeutic use; D013835:Thiamine Pyrophosphate / Q000494:pharmacology / Q000627:therapeutic use*
D000975:Antioxidants; D000995:Antitubercular Agents; D008315:Malondialdehyde; C024829:8-hydroxyguanine; D006147:Guanine; D004977:Ethambutol; D005978:Glutathione; D013835:Thiamine Pyrophosphate; D013831:Thiamine
Ethambutol; ocular toxicity; rat; thiamine pyrophosphate