Determination of potential role of antioxidative status and circulating biochemical markers in the pathogenesis of ethambutol induced toxic optic neuropathy among diabetic and non-diabetic patients

Abstract

The present study was designed to explore the antioxidative status and circulating biochemical markers having a potential role in the pathogenesis of ethambutol (EMB) induced toxic optic neuropathy (TON) among diabetic and non-diabetic patients. Fifty patients under complete therapy of EMB for tuberculosis were included in the present study. Inclusion criteria for patients were to receive EMB everyday during treatment, a dose of 25 mg/kg for initial 2 months and 15 mg/kg during the rest of therapy period. We conducted color vision and visual acuity test for all patients. Fifteen out of fifty EMB induced TON patients, were found to be diabetic. Color vision and visual acuity test results were evaluated for diabetic and non-diabetic as well as twenty age matched controls. The results demonstrated a significant pattern of circulating biochemical markers between the studied groups. Data regarding hematological (RBC, p value = 0.02; Hemoglobin, p value = 0.02), hepatic (total bilirubin, p value = 0.01), renal (urea, p value = 0.03; creatinine, p value = 0.007), lipid (total cholesterol, p value = 0.01; total triglycerides, p value = 0.03) and antioxidative (superoxide dismutase, p value = 0.005; glutathione, p value = 0.02; catalase, p value = 0.02) profile showed a highly significant difference among the studied groups specially patients with diabetes. Malondialdehyde (MDA) level had gone significantly up in diabetic TON patients (p value = 0.02), in comparison to other antioxidants and vitamins (Vit). Vit-A, E, B1, B12 and Zinc seem to be playing a major role in the pathogenesis of TON, specially Vit-E and B1 surpassed all the antioxidants as having highly significant inverse relationships with MDA (MDA vs Vit-E, r = -0.676(**) and MDA vs Vit-B1, r = -0.724(**) respectively). We conclude that during the ethambutol therapy the decreased levels of Vit-E and Vit-B1 possibly play a role in the development of TON and may be used as therapeutic agents to lessen the deleterious effects of ethambutol.

Neuroprotective potential of Lantana trifolium ethanolic extract against ethambutol induced histological changes in the optic nerve

“…A similar mechanism as described above of EMB metal chelating effect has been suggested as well for its induced axonal demyelination (Guillet et al, 2010) [38]. These changes result into vascular inflammation and thus a reduced blood supply to the nerve tissue that precedes myelin breakdown (Rasool et al, 2015) [10].…”

“…The exact mechanism of how EMB induces optic neuropathy has not been confirmed (Palomino and Martin, 2014) [9]. However it has been stipulated that it is due to the chelating effects of EMB and its metabolites that interfere with several mitochondrial metal containing enzymes (Rasool et al, 2015) [10]. This causes interruption of mitochondrial function and oxidative phosphorylation that result into optic nerve damage (Kinoshita et al, 2012) [11].…”

“…This causes interruption of mitochondrial function and oxidative phosphorylation that result into optic nerve damage (Kinoshita et al, 2012) [11]. The symptoms of EMB induced toxic optic neuropathy are painless, symmetrical and progressive (Rasool et al, 2015) [10]. The condition is underdiagnosed and the diagnosis is mostly done when recovery of vision is impossible (Jeanjean and Dupeyron, 2014) [12].…”

Role of oligodendrocytes in reversing ethambutol induced optic neuropathy

“…Oligodendrocytes, the major neuroglia in the optic nerve are responsible for production of myelin sheaths of the nerve fibres (Simons and Nave, 2016), which facilitates the rapid conduction of axons (Chamberlain et al, 2016) . Ethambutol induced toxic optic neuropathy is a symmetrical progressive painless condition, presenting with symptoms such as; blurring of vision, decrease in visual acuity (Rasool et al, 2015), bitemporal visual field scotoma defects, centro-caecal scotoma and disturbances in colour perception (Han et al, 2015 Although EMB toxicity is classically described as reversible on discontinuation with complete recovery over period of weeks to months (Holla et al, 2015), worsening of vision after EMB discontinuation has been observed in some patients (Garg et al, 2015). Previous studies have reported severe, and irreversible vision loss despite frequent monitoring and standard dosages (Chen, Lin, and Sheu, 2015).…”

“…Moreover, apart from stopping the use of EMB, there is no specific treatment available for alleviating EMB induced toxic optic neuropathy (Rasool et al, 2015). This study aimed at exploring the role of oligodendrocytes in reversing this condition by determining the effect of ethambutol toxicity on oligodendrocytes at different periods of treatment.…”