Evaluating the Genotoxicity Enhancement of the Antileukemic Drug 6-Mercaptopurin When Combined With Iraqi Nerium oleander and Narcissus tazetta Extracts in vivo

Abstract

The present study was aimed to evaluate the genotoxicity of the aqueous extracts of Nerium oleander leaves and Narcissus tazetta bulbs each alone and together with the antileukemic drug 6-Mercaptopurin (6MP) in order to investigate the extracts ability to elevate the chemotherapeutic drug genotoxicity which may influence its treatment of cancer.  The cytotoxicity test shows that the LD50 of the aqueous extract of Narcissus tazetta was 752.083 mg/kg and for Nerium oleander was 922.023 mg/kg. On the basis of the achieved LD50 values, the doses  92, 46 ,23 mg/kg of Nerium oleander and the doses  75, 37,18 mg/kg of Narcissus tazetta extracts were chosen, depending on chromosome aberrations, Micronuclei and Mitotic index as a powerful cytogenetic assays in bone marrow cells of Swiss albino male mice. The result indicated that Nerium oleander extract alone at the dose 92mg/kg induced significant effect on  centromere break and ring chromosome comparing with the negative control (untreated mice) and significantly increased the mean values of chromatid gap  and ring chromosome when  compared with the positive control ( 6MP ). While only the dose 46 mg/kg and 23 mg/kg of N. oleander aqueous extracts significantly decreased mitotic index and when combined with 6MP it can enhance its antimitotic activity but not significantly. Moreover the extracts alone and when combined with 6MP did not significantly change the total number of red blood micro nucleated cells. For Narcissus tazetta extract, the three experimental doses alone lead to significant increase in chromosomal aberrations like: chromatid break with fragment, chromatid break without fragment, chromatid gap, centromeric break, ring chromosome and dicentric chromosome. While only the dose 75mg/kg had induced significant structural chromosomal abnormalities such as chromatid break with fragment, chromatid break without fragment centromeric break and ring chromosome, when combined with 6MP.  The three doses of N. tazetta extract alone, had led to significant reduction in mitotic index compared with untreated control and also its combination with 6-MP significantly decreased the percentage of mitotic index. Moreover, only the doses 75 mg/kg and 37 mg/kg of N. tazetta extracts, when had given alone caused significant increase of the total micronucleated cells. While only the dose 75mg/kg of N. tazetta had induced significant frequency of the total micronucleated cell when combined with 6MP. In the present report, we attempted to establish that N.tazetta and Nerium oleander aquatic extracts enhance the genotoxicity and bioactivity induced by the  antileukemic drug  6MP , thus preventing the development of cellular drug resistance which is a major  problem that can face cancer patients using this drug .The current study serve the purpose of which is to search for local plants that may contribute to the establishment of novel supportive complementary and alternative medicine (CAM) during the chemotherapy of cancer in Iraq , Further studies are merited to explore this possibility.