Effect of vitamin B6 supplementation on gentamicin nephrotoxicity in rabbits

Therapeutic use of gentamicin (GM) in a clinical setting may result in nephrotoxicity, most commonly presenting as acute tubular necrosis (ATN). We have previously observed decreased plasma pyridoxal 5'-phosphate (PLP) levels in rabbits given therapeutic doses of GM and endeavor in this study to determine if vitamin B6 supplementation (B6S) could protect against the nephrotoxicity of GM. Twenty-one rabbits were randomly assigned to 1 of 7 treatment groups of 3 rabbits each. Three of the groups received 10 mg GM/kg with either 10 mg B6S, 100 mg B6S or 0.9% saline. Three of the groups received 40 mg GM/kg with either 10 mg B6S, 100 mg B6S, or normal saline. The control group only received 100 mg B6S. All treatments were administered im once daily for 5 d. Blood was drawn for chemical assays on day 0 prior to any treatments and 2 h after each respective treatment on days 1, 3 and 5. After 5 d, the rabbits were euthanatized and kidneys were excised for histological evaluation by light microscopy. At the 40 mg GM/kg/d dose, significant mild to moderate ATN was observed in the saline controls, which was prevented by either dose of B6S. Only a few animals given 10 mg GM/kg/d showed any renal pathology and that was minimal. Unexpectedly, 1 rabbit given only 100 mg B6S/d but no GM had interstitial nephritis with focal ATN. We conclude that vitamin B6 can protect against the nephrotoxicity of GM in rabbits, but that further study is needed on the possible nephrotoxicity of high doses of B6S.