1.
Differential efficacy of methylcobalamin and alpha-lipoic acid treatment on symptoms of diabetic peripheral neuropathy.
Han, Y, Wang, M, Shen, J, Zhang, Z, Zhao, M, Huang, J, Chen, Y, Chen, Z, Hu, Y, Wang, Y
Minerva endocrinologica. 2018;(1):11-18
Abstract
BACKGROUND Diabetic hyperglycemia damages peripheral nerves by triggering ischemia, oxidative stress, and inflammation. Alpha-lipoic acid (ALA) and methylcobalamin (MC) are known to improve signs of diabetic peripheral neuropathy (DPN), possibly by enhancing neural and vascular endothelial cell metabolism and antioxidant capacity. We evaluated differences in efficacy following short-term MC or ALA treatment on DPN symptoms to guide clinical drug selection. METHODS Forty DPN patients were randomly divided into MC and ALA treatment groups (both N.=20) and assessed by the Toronto Clinical Neuropathy Scoring System (TCSS), total symptom score (TSS), visual analog scale (VAS) of positive symptoms, and easy sensory test (EST) for negative symptoms before and after 2 weeks of treatment. Serum malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured. RESULTS Neuropathy as measured by TCSS, TSS, and VAS scores was significantly reduced by both treatments (P<0.05) but magnitude varied by symptom. The VAS score reductions for burning and pain were significantly greater following ALA (P<0.01), while MC reduced numbness and paresthesia VAS scores to a slightly greater extent than ALA (P>0.05). Numbers of abnormal (low-response) points for pressure and pinprick sensation were reduced by MC but not by ALA, while both treatments induced a significant reduction in vibratory perception threshold (P<0.01). Neither MC nor ALA improved temperature sensation or tendon reflexes (P>0.05). Alpha-lipoic acid, increased SOD and reduced MDA (P<0.05), indicating enhanced antioxidant capacity, while MC had no effect. CONCLUSIONS Due to differences in efficacy, MC or ALA should be chosen according to the symptoms of individual patients.
2.
The effect of an oral anti-oxidant, N-Acetyl-cysteine, on inflammatory and oxidative markers in pulmonary sarcoidosis.
Hamzeh, N, Li, L, Barkes, B, Huang, J, Canono, B, Gillespie, M, Maier, L, Day, B
Respiratory medicine. 2016;:106-11
Abstract
BACKGROUND Oxidative stress (OS) has been shown to play a role in the pathogenesis of sarcoidosis and previous studies have shown that anti-oxidants can reduce markers of oxidative stress and inflammation in the peripheral blood of sarcoidosis subjects. We investigated the effect of N-Acetyl-Cysteine (NAC) on oxidative stress and inflammatory markers in the lungs of sarcoidosis patients. METHODS We randomized 11 sarcoidosis subjects to active therapy and 3 to placebo for 8 weeks in a double blinded study. Bronchoscopy with bronchoalveolar lavage was performed pre and post therapy. Our primary endpoint was TNF-α production from stimulated and unstimulated BAL cells. Secondary outcomes included measures of oxidative stress (GSH, 8-OHdG) levels in the BAL. In-vitro studies were also performed to assess the effect of NAC on lipopolysaccharide stimulated BAL cell production of TNF-α. RESULTS Eight subjects in the active group and 2 in the placebo group completed the study protocol. Eight weeks of oral NAC did not have a significant impact on TNF-α levels from BAL cells in-vivo in spite of a 59% increase in BAL GSH levels. Our in vitro studies showed a significant decline in TNF-α production from LPS stimulated BAL cells treated with 5 and 10 mM of NAC. CONCLUSIONS Oral NAC increased GSH levels but failed to suppress in-vivo TNF-α production in contrast to effects in-vitro. Anti-oxidant therapy may still play a role in the management of sarcoidosis but therapy with better bioavailability or potency is needed to suppress the lung inflammatory response.