Methanol fraction of Calliandra portoricensis root bark activates caspases via alteration in mitochondrial viability in vivo

Introduction: Dysregulated apoptosis is associated with a number of disease conditions. Traditionally, Calliandra portoricensis is used in the management of prostate enlargement. This study investigates the in vivo effect of potent methanol fraction of C. portoricensis (MFCP) on mitochondrial permeability transition (mPT) pore, an important pharmacological target in treatment of various diseases, and examines the toxicities associated with its oral administration.Methods: Forty-two male Wistar strain rats (۷۰-۸۰ g) were divided into ۶ groups of ۷ animals each. Each group was orally administered ۲۵, ۵۰, ۱۰۰, ۲۰۰, ۴۰۰ mg/kg MFCP and the control group received distilled water for ۲۱ and ۳۰ days, respectively. mPT, assay for serum enzymes and hematological parameters were assessed spectrophotometrically while activation of caspases ۳ and ۹ was done by ELISA technique. Histological assessment of vital organs (liver, kidney, prostate) was carried out according to standard procedures.Results: There were no significant effects on mPT pore at all doses administered after ۲۱ days of oral administration. However, after ۳۰ days of administration, MFCP induced mPT pore opening at doses ۱۰۰ and ۲۰۰ mg/kg with induction folds of ۲.۶ and ۳.۳, respectively while there was no induction of mPT pore opening at lower doses of ۲۵ mg/kg and ۵۰ mg/kg. Furthermore, significant (P < ۰.۰۵) increases in serum enzymes (ALT, AST) were observed at all doses administered when compared with control after ۳۰ days of oral administration. Cell counts (Hb, PCV, RBC, WBC) were adversely affected at the highest dose (۲۰۰ mg/kg) compared with control and other treated groups (۲۵, ۵۰ and ۱۰۰ mg/kg) after ۳۰ days of administration. Similarly, activation of caspases ۹ and ۳ were observed in rat liver homogenate at high doses of the fraction while histological evaluation showed degeneration and distortion of organs at the highest dose.Conclusion: MFCP contains phytochemicals that elicit the opening of the pore and induction of mitochondrial-mediated apoptosis. This would be relevant in treatment of degenerative diseases that results from down-regulation of apoptosis. However, caution should be exercised in using high doses of the plant.