Low dose gamma irradiation modifies the effect of L-carnitine, curcumin, garlic powder and green tea extract on doxorubicin-induced nephropathy in rats

ABSTRACT

The possible protective potential of exposure to low dose of gamma radiation in presence or absence of L-carnitine, curcumin, garlic powder or green tea extract was examined in the present study on doxorubicin [DOX]-induced experimental nephropathy in rats. Preliminary study was carried out to select the suitable dose of DOX to induce nephrotoxicity. In the current experiment 5 mg/kg, i.p. was selected as a single dose to induce nephrotoxicity during 15 days. The possible modulating effect of L-carnitine, curcumin, garlic powder or green tea extract on kidney function was examined. Animals were subdivided into three sets. Three groups of the 1[st] set were exposed to [gamma] radiation at a single dose level of 0.3 Gy then received DOX, 1, 3 or 7 days postirradiation respectively. The groups of 2[nd] set daily received L-carnitine [40 mg/kg, i.p.], curcumin [50 mg/kg, i.p.], garlic powder [100 mg/kg, p.o.] and green tea extract [300 mg/kg, p.o.] daily for two weeks before induction of nephropathy. Groups of the 3[rd] set received the same doses of drugs then were injected with DOX, 1, 3 or 7 days following gamma irradiation respectively. Two groups of animals, one of them received saline and served as normal and the other received DOX and served as nephropathic group were included in 1[st], 2[nd] as well as 3[rd] set. Fifteen days following DOX administration, serum was collected and the animals were then sacrificed. Serum creatinine, urea and uric acid were evaluated. Data revealed that, a single DOX dose [5 mg/kg] induced marked acute nephrotoxicity manifested as significant increase in the activities of serum creatinine, urea as well as uric acid. Interestingly, pre-exposure to gamma radiation at a dose level of 0.3 Gy, 1 or 3 days before DOX injection exhibited significant improvement in the above altered mentioned parameters. However, exposure to low dose radiation 7 days prior to DOX administration did not show a protective effect. Moreover, pretreatment with L-carnitine, curcumin, garlic powder or green tea extract in rats unexposed or exposed to gamma radiation before DOX administration ameliorated, to a great extent, the effects induced by DOX. The present findings suggest that exposure to a single low dose of gamma radiation [0.3 Gy] one day before DOX administration is a promising approach for maximizing the nephroprotective effects of L-carnitine, curcumin, garlic powder or green tea extract with minimal adverse effects of DOX