ANNONA MURICATA ETHANOLIC LEAF EXTRACT POTENTIATES CYCLOPHOSPHAMIDE-INDUCED JEJUNAL TOXICITY

Ifeanacho Ezeteonu Abireh, Chiadikobi Lawrence Ozoemena* and Onisojime Moses Alasia

ABSTRACT

Objective: The practice of combination therapy of herbal concoctions with conventional medications is evident in Nigeria, however with numerous undesired effects. Annona muricata leaves alcohol-based concoctions have been deployed for the treatment of cancer and some other ailments, sometimes in combination with other cytotoxic drugs such as cyclophosphamide, thus, a heightened interest in understanding their possible synergism or mitigating effects in recent studies. Cyclophosphamide has been deemed cytotoxic and therefore in high concentrations can result in devastating effects on normal tissues. The same can be said for Annona muricata leaves, hence the need to establish the relationship between oral intake of ethanolic extract of Annona muricata leaves and cyclophosphamide in jejunal toxicity. Methods: A total of 24 male Wistar rats weighing between 180-250g were randomly grouped into six (A-F; n=4). Group A served as the normal control and received normal saline treatment only for 14 days. Group B received 50mg/kg BW of cyclophosphamide only on days 1 and 8 by intravenous route. Group C received oral administration of ethanolic extract of Annona muricata leaves at a dose of 50mg/kg BW considered to be a low-dose daily for 14 days. Groups D, E, and F were administered a weekly dose of 50mg/kg of cyclophosphamide on days 1 and 8 only via intravenous route, followed by daily oral administration of ethanolic extract of Annona muricata leaves for 14 days at 50mg/kg BW, 100mg/kg BW, and 150mg/kg BW respectively. Results: Malondialdehyde and Superoxide Dismutase levels were measured to determine the extent of oxidative stress in each group. Groups B and C demonstrated significant (p<0.05) differences compared to the normal control in the malondialdehyde analysis. The level of significance (p<0.05) in the reduced levels of superoxide dismutase seen in groups D-F compared to the rest of the groups was remarkable. This corresponded to the histological lesions characterized by severe depletion of the apical villi in groups E and F, suggesting ulcerative enteritis of the jejunum. Conclusion: Co-administration of Annona muricata leaf extract and cyclophosphamide should be discouraged as a means to prevent ulcerative enteritis during cancer therapies.

Keywords: Annona muricata leaves, Cyclophosphamide, Oxidative stress, Jejunal toxicity.