title: Effects of extracts of the leaves of Brysocarpus coccineus on rat liver mitochondrial membrane permeability transition (MMPT) pore.
abstract: OBJECTIVE
  To examine the influence or the effect of the extracts of Brysocarpus coccineus leaves on the mitochondrial membrane permeability transition (MMPT) pore opening in rats with a view to establishing if any bioactive constituent of the plant could become useful in the chemotherapy of cancer.
  
  
  METHODS
  The effects of extracts of the leaves of Brysocarpus coccineus, a medicinal plant with anti-tumour, anti-inflammatory and analgesic properties, were assessed on rat liver mitochondrial membrane permeability transition (MMPT) pore in the presence and absence of calcium in vitro and in vivo.
  
  
  RESULTS
  The results obtained show that calcium ions induced the opening of MMPT pore significantly (P < 0.05) in rat liver mitochondria, while spermine inhibited calcium-induced opening of pore, indicating that the mitochondria were intact ab initio. The results further revealed the inhibitory effects of different concentrations (200, 600, 1000, 1400, and 1800 microg/ml) of the various extracts of the leaves compared with spermine. Specifically, the data revealed that chloroform and ethylacetate extracts reversed calcium-induced opening of MMPT pore in a concentration-dependent manner (74%, 79%, 85%, 86%, 87%) for the chloroform extract and (36%, 37%, 59%, 71% and 83%) for the ethylacetate extract, respectively. On the contrary, pre-incubation of normal healthy mitochondria with the extracts in the absence of calcium resulted in the induction of the MMPT pore opening to varying degrees by these concentrations of the extracts. The chloroform extract induced pore opening in a concentration-dependent manner in the order 2.4, 2.4, 2.5, 2.6 and 3.0 folds while the ethylacetate extracts induced the opening of the pore by 1.1, 1.2, 1.3, 1.3 and 1.4 folds between 200-1800 microg/ml, respectively. The results obtained using rats orally exposed to various doses of methanol extract of the leaves of B. coccineus for fourteen days showed that there was significant (p < 0.05) induction of mitochondrial membrane permeability transition pore opening in the absence of calcium in a dose-dependent manner. Maximum induction of 26-fold was obtained at 200 mg/kgbwt while the least dose (50 mg/kgbwt) gave 17 fold induction.
  
  
  CONCLUSIONS
  The ability of the extracts of B. coccineus to induce MMPT pore opening in the absence of calcium in vitro and in vivo suggest that the leaves of the plant contain certain bioactive substances capable of inducing MMPT opening either in the original form or as formed biotrans derivative with eventual release of apoptotic proteins which may lead to apoptosis. The property of the extracts could be exploited for cancer chemotherapy when increased rate of apoptosis is required.
authors.affiliation: Laboratories for Biomembrane Research and Biotechnology, Biochemistry Department, College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors.forename: O T
authors.initials: OT
authors.lastname: Adedosu
authors.forename: T T
authors.initials: TT
authors.lastname: Adejoke
authors.forename: O O
authors.initials: OO
authors.lastname: Salako
authors.forename: O O
authors.initials: OO
authors.lastname: Olorunsogo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D031961:Connaraceae; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008099:Liver / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D053142:Mitochondrial Size / Q000187:drug effects / Q000502:physiology; D008933:Mitochondrial Swelling / Q000187:drug effects / Q000502:physiology; D010539:Permeability / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010936:Plant Extracts