Protective effect of Phyllanthus fraternus against mitochondrial dysfunction induced by co-administration of cisplatin and cyclophosphamide |
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Authors: | Kavita K Kumari O H Setty |
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Institution: | Centre for Biotechnology and Bioinformatics, School of Life Sciences, Jawaharlal Nehru Institute of Advanced Studies, Buddha Bhawan, Secunderabad 500003, Andhra Pradesh, India. kavita@jnias.in |
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Abstract: | The evolving role of mitochondria, in mediating chemotherapy-induced apoptosis motivated us for the studies described here.
The combination of cisplatin and cyclophosphamide is widely used in treating various types of cancers. The purpose of our
study was to understand the mechanism of the toxicity induced by the co-administration of cisplatin and cyclophosphamide,
on mitochondrial bioenergetics, and to study the protective effect of prior administration of the medicinal plant extract
Phyllanthus fraternus. Our results reveal that co-administration of cisplatin (12 mg/kg, i.p) and cyclophosphamide (150 mg/kg, oral) to wistar rats (100 g) significantly alters mitochondrial structure and hence function.
The rate of mitochondrial respiration was decreased significantly with both NAD + and FAD-linked substrates. The respiratory
control ratio, an index of membrane integrity and the P/O ratio, a measure of phosphorylating efficiency also were decreased
significantly accompanied by elevation in the lipid peroxide levels in liver, kidney homogenate and liver mitochondria respectively.
Also, the phospholipid content of the mitochondrial membrane, showed a significant decrease, indicating mitochondrial membrane
changes. Prior administration of an aqueous extract of P. fraternus (100 mg/kg) to rats, showed protection on all parameters investigated. Administration of P. fraternus alone did not show any significant changes on mitochondrial membrane bioenergetics. Thus, we propose, that the toxic side
effects of cisplatin + cyclophosphamide, are due to a chain of interconnected events, within the mitochondrial inner membrane, ultimately leading
to hepatotoxicity and nephrotoxicity. Further, our work also suggests that administration of aqueous extract of P. fraternus can enhance the therapeutic potential of anticancer drugs by reducing drug related toxicity. |
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