Neuroprotective Effect of p38 MAPKs Inhibitor (SB239063) and Vitamin B12 against Lipopolysaccharide Induced Neuroinflammation

Abstract Purpose To evaluate the effects of topical citicoline and vitamin B12 (OMK2, Omikron Italia srl, Italy) on the corneal sub-basal plexus density (SBP) of patients with diabetes. Methods This prospective, randomized, double blind, placebo-controlled study included thirty patients with diabetic neuropathy randomised with 2:1 ratio to OMK2 or placebo 3 times daily for 18 months. At baseline and at months 4,8,12,18 patients underwent the Ocular Surface Disease Index questionnaire (OSDI), tear break-up time, evaluation of corneal and conjunctival staining, Schirmer I test, Cochet-Bonnet esthesiometry, and confocal biomicroscopy of SBP. SBP density (mm/mm2) was calculated using NeuronJ. Raw data and differences from baseline were analysed in the two groups. Results 29/30 patients concluded the study. The two groups had similar SBP at baseline; it progressively improved up to month 18 in both groups (OMK2, p<0.0001; controls, <0.0001-0.03); improvement at month 18 vs baseline was higher in OMK2 than placebo (33% vs 15%, p=0.04). A progressive amelioration of corneal sensitivity was also shown just on OMK2 group (baseline, 28±18 mm; month 18, 52±10 mm, p<0.0001). In OMK2 patients, also conjunctival staining and OSDI questionnaire improved during the study (P=0.04 and 0.05). Both treatments were well tolerated and adherence during the study was high. Conclusions OMK2 ameliorated both morphology and function of corneal nerves in patients with diabetes, thus suggesting a neuroprotective effect.

Download Full-text

Neuroprotective effect of vitamin B6 and vitamin B12 against vincristine- induced peripheral neuropathy: A randomized, double- blind, placebo controlled, multicenter trial

10.1101/2021.05.18.21257296 ◽

2021 ◽

Author(s):

Fatiha Tasmin Jeenia ◽

Ferdaush Ahmed Sojib ◽

Md Sayedur Rahman ◽

Tasneem Ara ◽

Rafiquzzaman Khan ◽

...

Keyword(s):

Relative Risk ◽

Peripheral Neuropathy ◽

Vitamin B12 ◽

Risk Reduction ◽

Vitamin B6 ◽

Absolute Risk ◽

Neuroprotective Effect ◽

Induction Phase ◽

Double Blind ◽

Significant Difference

Background: Vincristine leads to development of debilitating neuropathy in 40-45% patients with resultant compromised efficacy of chemotherapy, suboptimal treatment and worse prognostic outcome. Vitamin B6 and vitamin B12 improves non- oncological neuropathies. Therefore, this study investigated vitamin B6 and vitamin B12 to prevent vincristine- induced peripheral neuropathy (VIPN) by reducing incidence, absolute risk, relative risk, severity as well as delaying the onset. Methods: Patients with ALL undergoing induction phase were randomly assigned into intervention or placebo arm in a double- blind manner. Vitamin B6 (25 mg Pyridoxine) two tablets were given three times daily for 5 weeks. Vitamin B12 (500 μg/ml Methylcobalamin) was administered intravenously on day 1, 3 and 5 of every week for 5 weeks during induction period. Placebo arm received oral and intravenous placebo for same duration. Patients were evaluated on the outset of every week by FACT/GOG-NTX questionnaire. Severity was assessed per NCI-CTCAE grading scale. Results: 102 patients were enrolled. Among them 81 completed the study, where 42 received vitamin B6 and B12 and 39 received placebo. There was significant difference in incidence of neuropathy between arms (26.19% intervention arm, 56.41% placebo; P-0.01). Relative risk of neuropathy was significantly (RR-0.46) lower in intervention arm. Besides, absolute risk reduction (ARR) was 30% and relative risk reduction (RRR) was 54%. NNT was 3.33. Significant trend was observed in difference of severity of VIPN between groups (P-0.03). No significant difference observed in between arms for time to onset of neuropathy. Conclusion: Vitamin B6 and vitamin B12 significantly reduced the incidence, relative risk and severity of VIPN. NNT was encouraging too. Henceforth, the status of vitamin B6 and vitamin B12 as neuroprotective agent against VIPN can be recommended as a promising one.

Download Full-text