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lymphocytes
Patrcia Danielle Lima de Lima1, Elizabeth Sumi Yamada2, Edmar Tavares da Costa2,
Claudia do O. Pessoa3, Silvia Helena Barem Rabenhorst4, Marcelo de Oliveira Bahia1,5,
Plnio Cerqueira Cardoso5, Raquel Alves Santos5, Marilia de Arruda Cardoso Smith6 and
Rommel Rodrguez Burbano1,6

The main mechanism for the toxicity of rotenone involves inhibition of complex I of the
mitochondrial respiratory chain. More specifically, rotenone blocks NADH oxidation by the
NADH-ubiquinone oxide reductase enzymatic complex, which results in the inhibition of
mitochondrial respiration and a reduction in the synthesis of ATP (Blandini et al., 1998; Fang and
Casida, 1999; Sestili et al., 1999; Chauvin et al., 2001). Rotenone treatment also results in the
production of reactive oxygen species, which can interact with proteins, DNA and RNA, altering
their functions or inducing lipidic peroxidation, eventually leading to cell death (Mizuno et al.,
1998; Suzuki et al., 1999; Barrientos and Moraes, 1999; Betarbet et al., 2000; Gao et al., 2002;
Li et al., 2003).
Mekanisme utama toksisitas rotenone melibatkan penghambatan kompleks I rantai pernafasan
mitokondria. Lebih spesifik lagi, rotenone menghambat oksidasi NADH oleh kompleks
enzimatik NADH-ubiquinon oksida reduktase, yang menghasilkan penghambatan respirasi
mitokondria dan pengurangan sintesis ATP (Blandini et al., 1998; Fang and Casida, 1999; Sestili
dkk. , 1999; Chauvin et al., 2001). Pengobatan rotenone juga menghasilkan produksi spesies
oksigen reaktif, yang dapat berinteraksi dengan protein, DNA dan RNA, mengubah fungsinya
atau menginduksi peroksidasi lipidik, yang akhirnya menyebabkan kematian sel (Mizuno et al.,
1998; Suzuki et al., 1999; Barrientos dan Moraes, 1999; Betarbet et al., 2000; Gao et al., 2002;
Li et al., 2003).
Pengertian Reactive Oxygen Species (ROS) adalah radikal bebas yang berupa oksigen dan
turunannya yang sangat reaktif.
ROS adalah beberapa jenis molekul dan radikal yang berasal dari molekul oksigen (O2) yang
digunakan dalam pernapasan
Efek toksik ROS
Pada DNA: modifikasi basa DNA atau pemotongan cincin DNA mengakibatkan penuaan,
kanker
Pada protein: inaktivasi enzim, depolarisasi protein mengakibatkan radang (inflamasi)

Rotenone inhibits cellular growth and division in many biological systems with
inhibitory effects on cell division observed at 10-100 nM concentrations in a
number of types of isolated cells. At least two possible mechanisms for this
antimitotic action have been described: a slowing of progression through the cell
cycle due to rotenone's effects on respiration and ATP availability, and a direct
effect on microtubule assembly and spindle formation which arrests cell division
in mitosis and resembles the effects of colchicine in disrupting spindle
formation.
Krieger, R. (ed.). Handbook of Pesticide Toxicology. Volume 2, 2nd ed. 2001.
Academic Press, San Diego, California., p. 1186

Rotenone inhibits mammalian cell proliferation by inhibiting

microtubule assembly through tubulin binding Pallavi Srivastava
and Dulal Panda School of Biosciences and Bioengineering, Indian
Institute of Technology, Mumbai, India
Rotenone, a widely used insecticide, has been shown to inhibit mammalian cell
proliferation and to depolymerize cellular microtubules. In the present study, the
effects of rotenone on the assembly of microtubules in relation to its ability to inhibit
cell proliferation and mitosis were analyzed.

Salahzadeh, 20002 (Rotenon 2)

Rotenone is a respiratory enzyme inhibitor, acting between NAD+ (a coenzyme
involved in oxidation and reduction in metabolic pathways) and coenzyme Q or
ubiquinone oxidoreductase (complex I) (Zhang et aI, 2001; Lummen, 1998). Since
this is a respiratory enzyme responsible for carrying electrons in some electron transport
chains, the result is failure of the respiratory functions. On the other hand
recent studies have suggested that there is a relationship between abnormality of
complex I in mitochondria and Parkinson's disease (Greenmyre et al, 2001)