The Effect of Alpha-Lipoic Acid on Mitochondrial Superoxide and Glucocorticoid-Induced Hypertension

Abstract

Aims. To examine the effect of alpha-lipoic acid, an antioxidant with mitochondrial superoxide inhibitory properties, on adrenocorticotrophic hormone- (ACTH-HT) and dexamethasone-induced hypertensions (DEX-HT) in rats and if any antihypertensive effect is mediated via mitochondrial superoxide inhibition. Methods. In a prevention study, rats received ground food or alpha-lipoic-acid-laced food (10 mg/rat/day) for 15 nights. Saline, adrenocorticotrophic hormone (ACTH, 0.2 mg/kg/day), or dexamethasone (DEX, 10 μg/rat/day) was injected subcutaneously from day 5 to day 11. In a reversal study, rats received alpha-lipoic-acid-laced food 4 days after commencement of saline or DEX. Tail-cuff systolic blood pressure (SBP) was measured second daily. Kidney mitochondrial superoxide was examined using (MitoSOX) Red (MitoSOX) via flow cytometry. Results. SBP was increased by ACTH (P < 0.0005) and DEX (P < 0.0005). Alpha-lipoic acid alone did not alter SBP. With alpha-lipoic acid pretreatment, SBP was increased by ACTH (P′ < 0.005) but not by DEX. Alpha-lipoic partially prevented ACTH-HT (P′ < 0.0005) and fully prevented DEX-HT (P′ < 0.0005) but failed to reverse DEX-HT. ACTH and DEX did not increase MitoSOX signal. In ACTH-hypertensive rats, high-dose alpha-lipoic acid (100 mg/rat/day) did not decrease SBP further but raised MitoSOX signal (P < 0.001), suggesting prooxidant activity. Conclusion. Glucocorticoid-induced hypertension in rats is prevented by alpha-lipoic acid via mechanisms other than mitochondrial superoxide reduction.

Exercise attenuates dexamethasone-induced hypertension through an improvement of baroreflex activity independently of the renin-angiotensin system

“…However, the exact mechanism associated with this effect is not completely understood. Some authors have suggested an involvement of nitric oxide, oxidative stress and atrial natriuretic factor in this response [4,22,23]. In agreement, we recently demonstrated that chronic treatment with low doses of DEX increased AP, and this response was associated with an autonomic imbalance to the heart and skeletal muscle rarefaction [15].…”

“…Despite its widespread use for allergies and inflammations, dexamethasone (DEX) induces several side-effects like hyperglycemia, muscle atrophy, baroreflex alterations, and hypertension [1][2][3][4]. Since hypertension is common in patients using glucocorticoid therapy [5], a better comprehension of the mechanisms responsible for this response is relevant in order to search for good strategies to control hypertension.…”

Biomolecular Modulation of Neurodegenerative Events during Ageing

“…Indeed, SOD, as well as MnSOD in particular, plays a major role in maintaining normal mitochondrial function and structural integrity [ 30 ]. It has been found that mutant mice totally lacking MnSOD suffer from severe mitochondrial defects, mainly in the brain and heart [ 12 , 31 , 32 ].…”

Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases

“…In one study a hormonal admixture of ALA was used [65]. The same was noted in animal studies with different purposes [10, 56, 63, 64, 67–72] when the doses used were described as percentage [63] to doses described as mg/rat [68] or described as mg/kg which ranged from 20 to 100 mg/kg [10, 69, 70, 72]. As observed in in vitro studies, most of the in vivo studies did not give an information about which type of ALA was used.…”

“…So far, only two clinical studies have addressed the use of ALA (600 mg/daily) in patients with AD, both studies were open-labeled [ 79 , 80 ]. One study was conducted with nine patients followed by 12 months [ 79 ] and the other with 43 patients followed by 24 months [ 68 ], both showing a slowing in the disease progression. Meanwhile, when ALA was associated with exercise training in animal model an increase in some antioxidant enzymes were observed [ 81 ].…”