We report the role of mitochondria in the protective effects of
curcumin, a well-known direct and indirect
antioxidant, against the renal
oxidant damage induced by the
hexavalent chromium [
Cr(VI)] compound
potassium dichromate (K(2)Cr(2)O(7)) in rats.
Curcumin was given daily by gavage using three different schemes: (1) complete treatment (100, 200, and 400 mg/kg
bw 10 days before and 2 days after K(2)Cr(2)O(7) injection), (2) pretreatment (400 mg/kg bw for 10 days before K(2)Cr(2)O(7) injection), and (3) posttreatment (400 mg/kg bw 2 days after K(2)Cr(2)O(7) injection). Rats were sacrificed 48 h later after a single K(2)Cr(2)O(7) injection (15 mg/kg, sc) to evaluate renal and mitochondrial function and
oxidant stress.
Curcumin treatment (schemes 1 and 2) attenuated K(2)Cr(2)O(7)-induced renal dysfunction, histological damage,
oxidant stress, and the decrease in
antioxidant enzyme activity both in kidney tissue and in mitochondria.
Curcumin pretreatment attenuated K(2)Cr(2)O(7)-induced
mitochondrial dysfunction (alterations in oxygen consumption,
ATP content,
calcium retention, and mitochondrial membrane potential and decreased activity of complexes I, II, II-III, and V) but was unable to modify renal and mitochondrial
Cr(VI) content or to chelate
chromium.
Curcumin posttreatment was unable to prevent K(2)Cr(2)O(7)-induced renal dysfunction. In further experiments performed in
curcumin (400 mg/kg)-pretreated rats it was found that this
antioxidant accumulated in kidney and activated Nrf2 at the time when K(2)Cr(2)O(7) was injected, suggesting that both direct and indirect
antioxidant effects are involved in the protective effects of
curcumin. These findings suggest that the preservation of mitochondrial function plays a key role in the protective effects of
curcumin pretreatment against K(2)Cr(2)O(7)-induced renal
oxidant damage.