Abstract:
:Daily subcutaneous administration of the oral hypoglycaemic agent, diphenyleneiodonium at a low dose (1.5 mg/kg body weight) over a 4-5 week period resulted in a normoglycaemic stable animal model of impaired oxidative phosphorylation in the rat. Diphenyleneiodonium specifically inhibits NAD-linked mitochondrial oxidation [Bloxham, Biochem. Soc. Trans. 7, 103 (1979)], and in isolated mitochondrial preparations from heart, soleus and gastrocnemius muscle and liver from treated animals NAD-linked respiration was reduced by 40% or more of mean control values. Brain and kidney mitochondria isolated from the treated group had similar rates of NAD-linked respiration to their respective control values. The activity of NADH-ferricyanide reductase was significantly reduced in all tissues tested, even in the isolated brain and kidney mitochondria where the activity in these tissues was 60-75% of control values. This suggests that at least 40% of Complex I activity must be inhibited before there is a decline in NAD-linked mitochondrial respiration. This paper discusses the use of diphenyleneiodonium as a means of establishing an animal model of the human disease state, termed mitochondrial myopathy.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Cooper JM,Petty RK,Hayes DJ,Morgan-Hughes JA,Clark JBdoi
10.1016/0006-2952(88)90143-8subject
Has Abstractpub_date
1988-02-15 00:00:00pages
687-94issue
4eissn
0006-2952issn
1873-2968pii
0006-2952(88)90143-8journal_volume
37pub_type
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