Protective Role of Aqueous Leaf Extract of Vernonia Amygdalina Del. (Asteraceae) And Ocimum Gratissimum Linn (Lamiaceae) in Cyclophosphamide Induced Urotoxicity and Myelosuppression

ABSTRACT Cyclophosphamide (CP) is one of the most potent and widely used alkylating anticancer agents. Urotoxicity and myelosuppression is known as the most prevailing dose-limiting toxicity associated with CP. In the present study, the protective potential of Vernonia amygdalina and Ocimum gratissimum aqueous leaf extracts in CP-induced urotoxicity and myelosupression were evaluated using biochemical and histopathological approaches. Sodium -2-macarptoethane sulfonate (MESNA) was used as a positive control. Forty (40) male Sprague-Dawley outbred albino rats weighing between 130 g – 200 g were randomly separated into eight different groups (n=5). Rats in group 1 received only normal saline orally for gavage for ten consecutive days. Animals in group two were injected with 5 CP only on the tenth day intraperitoneally (i.p) at 200 mg/kg body weight. Animals in group 3 were given MESNA (67 mg/kg) and CP (200 mg/kg) i.p on the tenth day at 5 minutes interval. Rats in groups 4 and 5 received two different doses of O. gratissimum orally by gavage at 250 mg/kg and 500 mg/kg respectively for ten consecutive days before administering CP (200 mg/kg) on the tenth day. Rats in group 6 and 7 received different doses of V. amygdalina orally by gavage at 250 mg/kg and 500 mg/kg respectively for ten consecutive days before administering CP (200 mg/kg) on the tenth day. Rats in group (8) received combination of V. amygdalina and O. gratissimum at a dose of 250 mg/kg each for ten consecutive before administering CP (200 mg/kg) on the tenth day. Results showed that the extract of V. amygdalina protected significantly (P < 0.05) the urothelium and the myeloid system as observed in the biochemical and hematological parameters evaluated. This protection is comparable to MESNA, but MESNA protection was not adequate to prevent myelosupression as observed with V. amygdalina. O. gratissimum did not show significant protection of the urothelium and myeloid system. The protective effects of V. amygdalina was further evident through decreased histopathological alteration of the urinary bladder, kidney and liver tissues unlike the CP and O. gratissimum treated groups. The result of the present study revealed that aqueous leaf extract of V. amygdalina has the potential to prevent urotoxicity and myelosuppression induced by CP and thus can be used as therapeutic adjuvant in the management of CP and other oxazaphosphorine toxicities.