Toxic Effects of Unripe Carica papaya (Linn) Fruit Extract on Healthy Rat Liver Mitochondria

Abstract

The opening of the mitochondrial Permeability Transition (mPT) pore proceeds the activation of programmed cell death (apoptosis) and its functional status serves as marker of mitochondrial health. Unripe fruits of Carica papaya are used in the traditional treatment of several diseases. There is paucity of information on the level of safety of the consumption of the plant. The effects of crude Methanol Extract of Carica papaya (MECP) on the status of the mPT pore in healthy rat liver was investigated in this study. Mitochondrial FOF1 ATPase activity, mitochondrial permeability transition and mitochondrial lipid peroxidation as well as the release of cytochrome c were evaluated spectrophotometrically using standard methods. The MECP activated mPT pore opening in the absence of calcium in a concentration-dependent fashion. Specifically, induction folds of 3.1, 6.0, 9.1, 11.9 and 14.3 were recorded at 20, 60,100, 140and 180 µg/ml, respectively. In addition, MECP potentiated calcium-induced pore opening of the mPT pore in a concentration-dependent style by 22.5, 24.1, 25.0, 25.1 and 25.5 folds, respectively at 20, 60, 100, 140 and 180 µg/mL. Furthermore, mitochondrial ATPase activity was significantly (p < 0.001) stimulated at pH (7.4) while the extent of cytochrome c release increased by 5 and 7 folds respectively at the highest concentrations tested. Interestingly, Fe2+-induced mitochondrial lipid peroxidation was inhibited by varying concentrations of MECP. Specifically, significant (p < 0.001) reduction in levels of mitochondrial lipid peroxides were observed at 50, 100, 200, 300, 600 µg/ml MECP by 10, 22, 53, 74, 112 %, respectively. These findings indicate that unripe Carica papaya fruit extract contains bioactive compounds that cause mitochondrial injury via activation of the mitochondrial permeability transition pore opening in healthy liver cells. Hence, its use in the management of diseases should be approached with caution.

Jatonik polyherbal mixture induced rat liver MMPT pore opening in normal Wistar rat: In vitro and in vivo studies

“…At varying concentrations of 4, 8, 12, 16 and 20 µg/mL of JME, MMPT pore was induced in a concentration-dependent manner by 569 %, 570 %, 545 %, 520 % and 457% at 4, 8 12, 16 and 20 µg/mL and having the highest induction at the lowest concentration while JEE also induced the pore opening but was decreased when compared with JME with 392%, 273%, 237%, 205%, and 151% at 20, 12, 4, 8 and 16 respectively. The observed opening could be due to mitochondria injury according to Oyebode and co-workers ( Oyebode et al, 2021 ). In contrast to JME, the highest induction was observed at 20 µg/mL for the JEE ( Fig.…”