ENHANCEMENT OF BONE-MARROW RADIOPROTECTION AND REDUCTION OF WR-2721 TOXICITY BY OCIMUM-SANCTUM

The radioprotective effect of the leaf extract of Ocimum sanctum (OE) in combination with WR-7721 (WR) was investigated on mouse bone marrow . Adult Swiss mice were injected intraperitoneally (i.p.) with OE (10 mg/kg on 5 consecutive days), or 100-400 mg/kg WR (single dose) or com bination of the two or double-distilled water (DDW) and whole-body exp osed to 4.5 Gy gamma-irradiation (RT). Metaphase plates were prepared from femur bone marrow on days 1, 2, 7 and 14 post-treatment and chrom osomal aberrations were scored. The maximum number of aberrant cells w as observed at 24 h after irradiation in all the groups. However, pret reatment with OE or WR individually resulted in a significant decrease in aberrant cells as well as different types of aberrations. The comb ination of the two further enhanced this effect; resulting in a 2-fold increase in the protection factor (PF = 6.68) compared to 400 mg/kg W R alone. The percent aberrant cells decreased linear-quadratically wit h WR dose when given individually, while in the OE + WR pretreatment a nimals the values showed a linear dose response. Combination of OE wit h WR doses above 200 mg/kg completely eliminated rings, polyploidy and pulverization of chromosomes. Percent aberrant cells decreased with t ime in all groups, though the values remained higher than normal even on day 14 in the RT alone as well as those treated with single agent RT. WR doses above 200 mg/kg before RT resulted in significantly hi h er frequency of aberrant cells compared to RT and OE + RT groups on da y 14, suggesting delayed WR toxicity; but combination of OE with WR br ought down these values to normal level, indicating that OE combinatio n. in addition to enhancing WR protection, may also act as a detoxifie r. The protective effect of OE and WR is also reflected in the enhance ment of bone marrow CFU survival. Both OE and WR possessed significant free radical scavenging activity in vitro. The combination of the two further enhanced this effect, suggesting that the enhanced free radic al scavenging activity by combining the two protectors results in the higher bone marrow cell protection. The significant elevation in chrom osome protection obtained by combining OE with WR, with reduction in t he latter's toxicity at higher doses, suggests that the combination ma y have promise for radioprotection in humans. (C) 1998 Elsevier Scienc e B.V.