Hormonal pretreatment preserves liver regenerative capacity and minimizes inflammation after partial hepatectomy

Impact of the Co-Administration of N-3 Fatty Acids and Olive Oil Components in Preclinical Nonalcoholic Fatty Liver Disease Models: A Mechanistic View

“…In view of these considerations, new therapeutic approaches were evaluated using the combination of bioactive compounds, a strategy that is characterized by (i) the use of lower doses of compounds than monotherapies with shorter supplementation periods to minimize possible side effects; and (ii) the involvement of compounds with protective effects that are exerted through different or similar mechanisms of action, thus allowing synergistic or additive actions and a more efficient control of the damaging effects [4,7]. For example, (i) preservation of liver tissue regeneration post-hepatectomy can be obtained by a L-3,3 ,5-triiodothyronine (T 3 ) plus methylprednisolone treatment [8]; (ii) high-fat diet (HFD)-induced liver steatosis can be diminished by n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) and extra virgin olive oil (EVOO) [9]; (iii) combined T 3 and fish oil supplementation suppresses ischemia-reperfusion inflammatory liver injury [10]; whereas (iv) resveratrol and enalapril improved glucose and lipid profiles by decreasing lipogenic gene expression [11]. Interestingly, an inverse correlation between serum free thyroxine (T 4 ) levels and hepatic steatosis was established in overweight and obese patients [12] or with elevated serum thyroid-stimulating hormone concentrations in overweight/obese children [13], while higher baseline levels of T 3 and T 4 predict more weight loss, but not weigh regain, in overweight/obese patients with normal thyroid function subjected to weight loss diets [14].…”

Redox signaling associated with thyroid hormone action: perspectives in medical sciences

“…The beneficial effects of THs are not only exerted against IR injury [11,19], but also on other stressful conditions evidenced in preclinical studies. In this respect, liver tissue regeneration after 70% hepatectomy was favored by pretreatment with T 3 combined with methylprednisolone, with concomitant reductions in ALT serum levels, liver oxidized protein content, inflammation and necrosis foci being observed over control values [55], which are in agreement with the upregulation of the proteins involved in the control of cell cycle by T 3 [56]. In addition, brain-dead rats pretreated with T 3 and exhibiting lower circulating levels of ALT and AST, showed diminished Bax gene expression and cleaved Caspase-3 activation compared to control animals, supporting the protective and anti-apoptotic PC action of T 3 in the liver of brain-dead rats [57].…”

Docosahexaenoic acid‐thyroid hormone combined protocol as a novel approach to metabolic stress disorders: Relation to mitochondrial adaptation via liver PGC‐1α and sirtuin1 activation

“…This contention is primarily based in that combined protocols employ lower doses of therapeutic agents than those in monotherapies, with shorter supplementation periods, thus minimizing possible adverse effects, and that the mechanisms involved may trigger different underlying processes or similar mechanisms exhibiting synergism . In experimental animals, (a) liver ischemia–reperfusion (IR) inflammatory injury is prevented by L‐3,3′,5‐triiodothyronine (T 3 ) plus n‐3 long‐chain polyunsaturated fatty acid (n‐3 LCPUFA) administration ; (b) liver tissue regeneration post hepatectomy is preserved in rats subjected to T 3 plus methylprednisolone, minimizing the concomitant inflammatory, and oxidative stress responses ; and (c) high‐fat diet (HFD)‐induced liver steatosis is attenuated in mice supplemented with an n‐3 LCPUFA and extra virgin olive oil mixture . Remarkably, higher serum baseline T 3 and T 4 levels associated with weight loss diets predict more weight loss, but not weight regain, in overweight and obese patients with normal thyroid function , while combined drug protocols are suggested for uncontrolled hypertension to normalize blood pressure and increase the adherence to therapy .…”