title: Supplementation of T3 recovers hypothyroid rat liver cells from oxidatively damaged inner mitochondrial membrane leading to apoptosis.
abstract: Hypothyroidism is a growing medical concern. There are conflicting reports regarding the mechanism of oxidative stress in hypothyroidism. Mitochondrial oxidative stress is pivotal to thyroid dysfunction. The present study aimed to delineate the effects of hepatic inner mitochondrial membrane dysfunction as a consequence of 6-n-propyl-2-thiouracil-induced hypothyroidism in rats. Increased oxidative stress predominance in the submitochondrial particles (SMP) and altered antioxidant defenses in the mitochondrial matrix fraction correlated with hepatocyte apoptosis. In order to check whether the effects caused by hypothyroidism are reversed by T3, the above parameters were evaluated in a subset of T3-treated hypothyroid rats. Complex I activity was inhibited in hypothyroid SMP, whereas T3 supplementation upregulated electron transport chain complexes. Higher mitochondrial H2O2 levels in hypothyroidism due to reduced matrix GPx activity culminated in severe oxidative damage to membrane lipids. SMP and matrix proteins were stabilised in hypothyroidism but exhibited increased carbonylation after T3 administration. Glutathione content was higher in both. Hepatocyte apoptosis was evident in hypothyroid liver sections; T3 administration, on the other hand, exerted antiapoptotic and proproliferative effects. Hence, thyroid hormone level critically regulates functional integrity of hepatic mitochondria; hypothyroidism injures mitochondrial membrane lipids leading to hepatocyte apoptosis, which is substantially recovered upon T3 supplementation.
authors.affiliation: Department of Zoology, Utkal University, Bhubaneswar, Odisha 751004, India ; Department of Zoology, Visva-Bharati (A Central University), Santiniketan, West Bengal 731235, India.
authors.forename: Sutapa
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Zoology, Utkal University, Bhubaneswar, Odisha 751004, India ; Department of Zoology, Ravenshaw University, Cuttack, Odisha 753003, India.
authors.forename: Luna
authors.initials: L
authors.lastname: Samanta
authors.affiliation: Department of Biotechnology, Utkal University, Bhubaneswar, Odisha 751004, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Roy
authors.affiliation: Department of Biotechnology, Utkal University, Bhubaneswar, Odisha 751004, India.
authors.forename: Shravani
authors.initials: S
authors.lastname: Bhanja
authors.affiliation: Department of Zoology, Utkal University, Bhubaneswar, Odisha 751004, India ; Department of Biotechnology, Utkal University, Bhubaneswar, Odisha 751004, India.
authors.forename: Gagan B N
authors.initials: GB
authors.lastname: Chainy
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D042967:Electron Transport Complex I / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D020249:Hormone Replacement Therapy; D006861:Hydrogen Peroxide / Q000378:metabolism; D007037:Hypothyroidism / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism* / Q000473:pathology; D051336:Mitochondrial Membranes / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000627:therapeutic use*
chemical_list: D014284:Triiodothyronine; D006861:Hydrogen Peroxide; D042967:Electron Transport Complex I; D005978:Glutathione