title: Corrections by melatonin of liver mitochondrial disorders under diabetes and acute intoxication in rats.
abstract: The aim of the present work was to investigate the mechanisms of oxidative damage of the liver mitochondria under diabetes and intoxication in rats as well as to evaluate the possibility of corrections of mitochondrial disorders by pharmacological doses of melatonin. The experimental (30 days) streptozotocin-induced diabetes mellitus caused a significant damage of the respiratory activity in rat liver mitochondria. In the case of succinate as a respiratory substrate, the ADP-stimulated respiration rate V₃ considerably decreased (by 25%, p < 0·05) as well as the acceptor control ratio (ACR) V₃/V₂ markedly diminished (by 25%, p < 0·01). We observed a decrease of the ADP-stimulated respiration rate V₃ by 35% (p < 0·05), with glutamate as substrate. In this case, ACR also decreased (by 20%, p < 0·05). Surprisingly, the phosphorylation coefficient ADP/O did not change under diabetic liver damage. Acute rat carbon tetrachloride-induced intoxication resulted in considerable decrease of the phosphorylation coefficient because of uncoupling of the oxidation and phosphorylation processes in the liver mitochondria. The melatonin administration during diabetes (10 mg·kg⁻¹ body weight, 30 days, daily) showed a considerable protective effect on the liver mitochondrial function, reversing the decreased respiration rate V₃ and the diminished ACR to the control values both for succinate-dependent respiration and for glutamate-dependent respiration. The melatonin administration to intoxicated animals (10 mg·kg⁻¹ body weight, three times) partially increased the rate of succinate-dependent respiration coupled with phosphorylation. The impairment of mitochondrial respiratory plays a key role in the development of liver injury under diabetes and intoxication. Melatonin might be considered as an effector that regulates the mitochondrial function under diabetes.
authors: Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Grodno, Belarus.
authors: Vitali T
authors: VT
authors: Cheshchevik
authors: Iosif K
authors: IK
authors: Dremza
authors: Elena A
authors: EA
authors: Lapshina
authors: Svetlana V
authors: SV
authors: Zabrodskaya
authors: Jolanta
authors: J
authors: Kujawa
authors: Ilya B
authors: IB
authors: Zavodnik
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000209:etiology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D056152:Respiratory Rate / Q000187:drug effects
chemical_list: D000244:Adenosine Diphosphate; D002251:Carbon Tetrachloride; D008550:Melatonin