Table 2.
Summary of in vivo studies testing cellular and molecular effects of LA.
| Experimental model | Regimen of treatment | Effects | References |
|---|---|---|---|
| Aging | Chronic, α-LA (100 mg/kg body weight, orally for 15 days | LA alleviated age-related NMDA receptor deficits (Bmax) | Stoll et al., 1993 |
| Aging | Acute and Chronic, DL-α-LA (100 mg/kg body weight/day), 7 or 14 days, young and aged rats, intraperitoneally | ↓ lipid peroxidation, ↑ levels of antioxidants in various brain regions | Arivazhagan and Panneerselvam, 2000 |
| Aging | α-LA (300 mg/kg/day) for 6weeks | ↓ mtDNA deletions associated with aging | Seidman et al., 2000 |
| Aging | Acute and Chronic, DL-α-LA (100 mg/kg body weight/day), 7 or 14 days, young and aged rats, intraperitoneally | ↑levels of neurotransmitters (dopamine, serotonin and norepinephrine) in various brain regions | Arivazhagan and Panneerselvam, 2002 |
| Aging | Acute and Chronic, DL-α-LA (100 mg/kg body weight/day), 7 or 14 days, young and aged rats, intraperitoneally | ↓ level of lipid peroxidation, ↑activities of antioxidant enzymes in various brain regions | Arivazhagan et al., 2002 |
| Aging | R-α-LA [0.2% or 0.1% (wt/wt) in diet] for 7 weeks | ↓ reduced the extent of oxidized RNA, reversed age-associated mitochondrial structural decay | Liu et al., 2002a |
| Aging | R-α-LA [0.2% (wt/wt) in diet] for 7 weeks | Inhibited lipid peroxidation but did not decrease iron and copper levels | Liu et al., 2002b |
| SAMP8 accelerated aging mice | Chronic, LA (100 mg/kg), subcutaneously for 4 weeks | ↓Protein carbonyl levels, ↑W/S ratio, ↓TBARS levels | Farr et al., 2003 |
| Abeta peptide vaccination-induced inflammation | Acute, LA (100 mg kg −1 body weight), intraperitoneally for 4 days | ↑ levels of 5-HT, DA and NE and the concentration of 5-HIAA and HVA gradually returned to normal | Jesudason et al., 2005 |
| SAMP8 accelerated aging mice | Chronic, LA as a racemic mixture (100 mg/kg body weight) daily, 4 weeks, subcutaneously | ↑ brain proteins (neurofilament triplet L protein, α-enolase, and ubiquitous mitochondrial creatine kinase), ↓ specific carbonyl levels of the three brain proteins (lactate dehydrogenase B, dihydropyrimidinase-like protein 2, and α-enolase) | Poon et al., 2005 |
| Aging | Chronic, LA (0.2% [w/w]) for 2 weeks | ↓cerebral iron levels, antioxidant status and thiol redox state improved markedly | Suh et al., 2005 |
| Adult male C57BL/6 mice with D-gal administration | Chronic, α-LA (100 mg/kg body weight) daily, 7 weeks, intraperitoneally | Ameliorated neurodegeneration in the hippocampus, ↓ peripheral oxidative damage, ↑ T-AOC and T-SOD, no effect on GSH-Px, ↓ caspase-mediated apoptosis, ↑ neurogenesis and neuron migration, ↓oxidative | Cui et al., 2006 |
| Reserpine rat model of PD | Acute, LA (50 mg/kg) administered twice, 30 min before and after reserpine injection, intraperitoneally | ↑ concentration of GSH and ↓GSSG level in the striatum, ↑ GSH level and no changes in GSSG content in the prefrontal cortex, ↓ NO concentrations, ↑ Enzymatic activities of GPx and GST in the striatum | Bilska et al., 2007 |
| MPTP model of PD | Acute, α-LA (22 mg/kg body weight, sc) twice daily, concomitant with MPTP | Abolished the activation of ASK1 and phosphorylation of downstream kinases, MKK4, and JNK and prevented the down-regulation of DJ-1 and translocation of Daxx to the cytosol; attenuated dopaminergic cell loss in SNpc | Karunakaran et al., 2007 |
| Cognitive impairment induced by radiation | Sub-chronic, LA (200 mg/kg bw) intraperitoneally for 5 days | Protected against augmentation of protein carbonyls and TBARS in cerebellum; intact cytoarchitecture of cerebellum, higher counts of intact Purkinje cells and granular cells; T-SH, NP-SH, PB-SH contents of cerebellum and plasma FRAP was inhibited | Manda et al., 2007 |
| Aging | Chronic, α-LA (100 mg/kg body weight/day dissolved in alkaline saline) for 30 days | Old rats: ↓ levels of mitochondrial LPO, 8-oxo-dG and oxidized glutathione and enhanced reduced glutathione, ATP, lipoic acid and ETC complex activities; Young rats: ↓ levels of LPO, 8-oxo-dG and oxidized glutathione and ↑levels of reduced glutathione, ATP, lipoic acid, TCA cycle enzymes and ETC complex activities. | Palaniappan and Dai, 2007 |
| Tg2576 AD mouse model | Chronic, fed an α-LA-containing (0.1%) for 6 months | No effects on β-amyloid levels or plaque deposition | Quinn et al., 2007 |
| Aging | Acute, LA (10, 20 or 30 mg/kg, i.p.), 24 h | ↓ lipid peroxidation level, no alteration was observed in SOD activity, ↑ DA and NE, ↓ 5-HT and their metabolites 5-HIAA, the metabolites (DOPAC and HVA) did not differ in hippocampus | Ferreira et al., 2009 |
| Tg2576 AD mouse model | Chronic, LA (diet 30 mg/kg per day) for 10 months | ↓expression of HO-1 and protein-bound HNE, ↓ HO-1 around amyloid plaques, ↓ protein-bound HNE expression surrounding Aβ plaques, Redox active iron accumulation was specifically co-localized with Aβ plaques in the hippocampus and cortical regions | Siedlak et al., 2009 |
| Pilocarpine-induced seizures | Acute, LA (20 mg/kg, ip) for 30 min | ↓ lipid peroxidation and nitrite concentrations and ↑SOD, CAT and GPx activities in striatum | Militao et al., 2010 |
| AlCl3 rat model of AD | Chronic, α-LA (100 mg/kg/day for 3 months) after AlCl3 (100 mg/kg b.wt/day for 4 months), orally. | ↓ AChE activity, ↓ inflammation, ↑ neuronal and regeneration features | Ahmed, 2012 |
| SAMP8 accelerated aging mice | Chronic, LA (100 mg/kg), subcutaneously for 4 weeks | ↑GSH, ↓MDA, ↓GPx | Farr et al., 2012 |
| Rotenone rat model of PD | Sub-chronic, α-LA (50 mg/kg/day/12 doses[12 days], po) | ↑striatal dopamine level, no effect on striatal ATP level, ↓ level of lipid peroxides and ↓protein carbonyls in rat brains, ↑tissue GSH, improved injury to mtDNA and normalization of the mtDNA content, ↑ percentage of SNpc dopaminergic neurons, ↑ number of Nissl stained neurons | Zaitone et al., 2012 |
| DBA/2J mouse model of glaucoma | 60 mg/kg body weight (bw)/day for the intervention study and 100 mg/kg bw/day for the prevention study in diet for 24 months | ↑antioxidant gene and protein expression, ↑protection of RGCs and improved retrograde transport, ↓ lipid peroxidation, ↓ protein nitrosylation, ↓ DNA oxidation in the prevention and intervention paradigms. | Inman et al., 2013 |
| Unilateral intrastriatal 6-OHDA-lesioned rats | 50 and/or 100 mg/kg 24 h before surgery | Prevented loss of SNC neurons, ↓ levels of MDA and nitrite | Jalali-Nadoushan and Roghani, 2013 |
| 3 × Tg-AD | Chronic, LA (0.23% w/v in drinking water) for 4 weeks | ↑brain glucose uptake; ↑ in the total GLUT3 and GLUT4 in the old mice; activation of the insulin receptor substrate and of the PI3K/Akt signaling pathway; changes in synaptic function (↑I/O) and LTP. | Sancheti et al., 2013 |
| Arsenic-dichlorvos exposed rats | Chronic, α-LA (50 mg/kg/day for 10 months), orally. | Oxidative stress and cholinergic dysfunction was protected | Dwivedi et al., 2014 |
| Lipolysaccharide (LPS)-induced inflammatory PD model | Sub-chronic, LA (100 mg/kg/d) administered ip for 30 days | Protected dopaminergic neurons loss, ↓α-synuclein accumulation in the substantia nigra, inhibited the activation of NF-κB and expression of pro-inflammatory molecules in M1 microglia | Li et al., 2015 |
| 3-NP-induced HD model of | Chronic, α-LA (50 mg/kg), intraperitoneally for 21 days | Restored respiratory chain enzyme activities, CAT activity was improved, normalized of mitochondrial appearance, stimulated the repair of mitochondrial membranes and restored functionality to impaired mitochondria, ↓lipid peroxidation, ↓protein carbonyls, ↓ROS and nitrite levels, ↓cytosolic levels of cytochrome c, ↓activities of caspase-3 and 9. | Mehrotra et al., 2015 |
| AlCl3-induced neurotoxicity mouse model | Sub-chronic, α-LA mixed in diet (200 ppm = dose of 25 mg/kg/day) for 12 days | Improves the expression of muscarinic receptors (M1 and M2) and choline acetyltransferase | Mahboob et al., 2016 |
3-NP, 3-nitropropionic acid; 5-HIAA, 5-hydroxyindoleacetic acid; 5-HT, 5-hydroxytryptamine; 5-HT, serotonina; 6-OHDA, 6-hydroxydopamine; 8-oxo-dG, monoclonal anti-8-hydroxyguanine; AChE, acetylcholinesterase; AD, Alzheimer's disease; AlCl3, Aluminum chloride: ASK1, apoptosis signal regulating kinase 1; Aβ, amyloid-β fibrils; CAT, catalase activity; DA, dopamine; D-gal, D-galactose; DOPAC, 3,4-hydroxyphenylacetic acid; ETC, electron transport chain; FRAP, ferric reducing power; GLUT3, glucose transporter 3; GLUT4, glucose transporter 4; GPx, glutathione peroxidase; GSH, reduced glutathione; GSH-Px, glutathione peroxidase; GSSG, glutathione disulfide; GST, glutathione-S-transferase; HNE, 4-hydroxynonenal; HO-1, heme oxygenase-1; HVA, homovanillic acid; I/O, input/output; JNK, Jun N-terminal kinase; LPO, lipid peroxidation; LPS, Lipolysaccharide; LTP, long term potentiation; M1,Type 1 macrophages/microglia; M2, Type 2 macrophages/microglia; MDA, malondialdehyde; MKK4, mitogen-activated protein kinase kinase 4; MPTP, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine; mtDNA, mitochondrial DNA; NE, norepinephrine; NF-κB, nuclear factor-κB; NMDA receptor, N-methyl-D-aspartate receptor; NO, nitric oxide; PD, Parkinson's disease; RGC, retinal ganglion cell; ROS, reactive oxygen species; SNC, substantia nigra pars compacta; SNpc, substantia nigra pars compacta; SOD, total superoxide dismutase; T-AOC, total antioxidative capabilities; TBARS, thiobarbituric acid reactive substance; T-SOD, total superoxide dismutase; W/S, weakly immobilized/strongly immobilized.