Antioxidant protecting effects of vitamin B6 at reducing hemodynamic toxicity of gentamicin in rat model of nephrotoxicity

Abstract

Routine therapeutic use of gentamicin in patients with preexisting renal failure may confront us with the toxic effects of aminoglycosides in the kidney known as nephrotoxicity. It is a common and often overlooked clinical entity that presents itself in the setting of oxidative stress-associated diseases in older individuals with renal failure. In this study, we investigated the antioxidant protecting effects of vitamin B6 in the kidney, with a view on vasoregulatory role of renal pyridoxal 5′-phosphate at reducing the hemodynamic toxicity of gentamicin. Hence, 50 male Sprague–Dawley rats were randomly assigned in five groups to receive a corresponding dose of either normal saline, vitamin B6 (100 mg/kg/bw; i.m.) or gentamicin alone (80 mg/kg/bw; i.m.), or in combination with vitamin B6 at low (100 mg/kg/bw; i.m.) and high dose (200 mg/kg/bw; i.m.) for 10 days as animal model of nephrotoxicity. Daily administration of gentamicin at a dose of 80 mg/kg resulted in a significant increase in local and systemic oxidative stress and a decrease in glomerular functions as result of early hemodynamic toxicity. Histopathological examinations of renal tissues revealed acute tubular necrosis with hyaline cast formation triggered by gentamicin over 9 days of the experiment, in addition to interstitial nephritis and tubular epithelial loss. Further biochemical studies in HVB group showed the protecting effects of supplemented vitamin B6 at a high dose, including a slowdown in urinary enzyme activity, a significant decrease in plasma lipid peroxidation, and an increased tissue superoxide dismutase activity with recovery in the glomerular hemodynamicity and ATPase activity up to 50 % when compared to low-dose rats and controls. In high-dose animals, normal glomerular and tubular function on recovery from toxic renal failure led us to conclude that antioxidant properties of vitamin B6 consistently increase with dose intensity. The present study also provided evidence that high dose of vitamin B6 prevented both functional and histological renal changes induced by gentamicin in rats, more efficient than low dose of the vitamin.