EFFECTS OF VITAMIN B COMPLEX THERAPY ON TEMPORAL VARIATION IN GENTAMICIN NEPHROTOXICITY IN WISTAR RATS
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ABSTRACT
The efficacy and toxicity of several drugs is circadian-rhythm dependent, and this can be exploited as a guide to ameliorate such drug toxicity. Gentamicin is an aminoglycoside antibiotic used in treatment of a variety of infections. Its use is however limited by its associated nephrotoxicity. This nephrotoxicity is ameliorated by reduction in dosing frequency to once a day dosing, use of antioxidants and exploration of circadian variation in gentamicin nephrotoxicity. Temporal variation in gentamicin nephrotoxicity and the use of antioxidants at the time of highest nephrotoxicity are alternative ameliorative strategies for this established toxicity. This study compares the effect of concurrent administration of vitamin B complex and gentamicin based on its temporal variation in nephrotoxicity, with alternative approaches of use of a single strategy alone. Young wistar rats of both sexes were used in this study. A nephrotoxic dose of gentamicin was determined from a ten day study with 80, 100 and 120 mg/kg intraperitoneal gentamicin administration using selected biomarkers as indices. Nephrotoxicity was accessed by elevation of serum urea and serum creatinine which are biomarkers of nephrotoxicity and histological changes of the kidney. Administration of 100 mg/kg of gentamicin at 0800, 1200, 2000 and 0000 hours resulted in nephrotoxicity with maximal toxicity observed at 1200 hours where the level of serum urea and creatinine differed significantly (p≤0.05) from the normal saline control and minimal toxicity was seen at the 0000 hour. Histology of the kidneys showed lymphocyte hyperplasia, interstitial haemorrhages, tubular and glomerular necrosis in the 1200 hour group which was observed to be mild in the 0000 hour group. No significant change was seen in the levels of serum electrolytes (Na+ , K+ , Cl+ , Ca2+) and liver function enzymes (ALT, AST and ALP) irrespective of time of treatment. Concurrent administration of vi gentamicin and vitamin B complex at 1200 and 0000 hours resulted in amelioration of gentamicin nephrotoxicity. However, the amelioration produced by the administration of gentamicin alone at the time of minimal toxicity (0000 hour) was greater than that produced by concurrent administration of gentamicin and vitamin B complex at this time point. The administration of gentamicin based on its temporal variation in nephrotoxicity offers better amelioration of nephrotoxicity than concurrent administration of gentamicin at the time of highest toxicity with vitamin B complex in wistar rats.
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