Mitochondrial transplantation via injection of exogenous mitochondria into blood reduces bleomycin-induced oxidative damages and mitochondrial dysfunction in lung tissue

Abstract

Mechanistic studies have been suggested that adverse effect of bleomycin is attributed to formation of free radicals, mitochondria damages, oxidative stress and inflammation in lung tissue. Mitochondria act as central regulators in the oxidative stress and inflammatory responses in lung tissue, then it can be a promising approach for management bleomycin-induced pneumotoxicity. In the current study, we aim to investigated the injection of exogenous mitochondria into blood as one of the most promising pharmacological approaches to reduce bleomycin-induced lung toxicity in rats. Rats were divided into 4 groups as control, bleomycin (5 mg/kg), bleomycin + mitochondria (250 µg/kg), and mitochondria (250 µg/kg) alone. After 2 weeks, the survival rate, weight changes of animals, wet/dry ratio of lung tissue, alterations of histopathology, hydroxyproline content, oxidative stress and mitochondrial biomarkers were determined. Except the survival rate, weight changes of animals and wet/dry ratio of lung tissue, administration of bleomycin resulted in significant alteration in GSH content, MDA level, hydroxyproline amount, collapse of mitochondrial membrane potential (MMP), reduction of succinate dehydrogenases (SDH) activity and histopathological abnormality in comparison with control group. While exogenous mitochondria could inhibit GSH depletion, reduce production of MDA, improve the activity of SDH, prevent loss of MMP and histopathological abnormality. To the best of our knowledge, our data provides the first direct experimental evidence that injection of exogenous mitochondria into blood is capable of ameliorating bleomycin-induced lung toxicity in rats. These findings support that mitochondrial transplantation can be a promising therapeutic strategy for bleomycin-associated mitochondrial dysfunction and lung damage.