The role of flaxseed and vitamin E on oxidative stress in prepubertal rats with experimental varicocele: An experimental study

Background: Prepubertal varicocele has the most devastating effects on the testes. Oxidative stress is the major cause leading to infertility in varicocele. The antioxidant properties of Flaxseed (FS) treatment in some oxidative diseases have been reported. Objective: This study aimed to evaluate the antioxidant effect of FS in prepubertal rats with experimental varicocele. Materials and Methods: Forty two male prepubertal rats were divided into 6 groups: the varicocele group were either fed with 10% FS, or with regular diet, or with Vit E, the group with sham operation fed with 10% FS, or had regular diet, and control rats who had not been operated but received regular diet. Varicocele was created by Koksal method. After 6 weeks sperm superoxide anion and H2O2 were evaluated by flowcytometery. Semen total antioxidant capacity (TAC) by Koracevic method and testes malondialdehyde (MDA) by thiobarbituric acid with spectrophotometry was measured. Results: While superoxide anion and H2O2 were significantly higher in varicocele grop with regular diet (p=0.0001), FS significantly decreased the previously-mentioned parameters (p=0.0001). There were no significant differences for seminal TAC between 6 groups (p=0.07). Left testicular MDA concentration were lower in varicocele or group that were fed with 10% FS compared with other groups (p=0.001). Conclusion: Reactive oxygen species (ROS) may cause sperm oxidative damage. FS as a fat soluble antioxidant can scavenge intracellular ROS production in varicocele

Homotaurine, a safe blood-brain barrier permeable GABAA-R-specific agonist, ameliorates disease in mouse models of multiple sclerosis

Abstract There is a need for treatments that can safely promote regulatory lymphocyte responses. T cells express GABA receptors (GABAA-Rs) and GABA administration can inhibit Th1-mediated processes such as type 1 diabetes and rheumatoid arthritis in mouse models. Whether GABAA-R agonists can also inhibit Th17-driven processes such as experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), is an open question. GABA does not pass through the blood-brain barrier (BBB) making it ill-suited to inhibit the spreading of autoreactivity within the CNS. Homotaurine is a BBB-permeable amino acid that antagonizes amyloid fibril formation and was found to be safe but ineffective in long-term Alzheimer’s disease clinical trials. Homotaurine also acts as GABAA-R agonist with better pharmacokinetics than that of GABA. Working with both monophasic and relapsing-remitting mouse models of EAE, we show that oral administration of homotaurine can (1) enhance CD8+CD122+PD-1+ and CD4+Foxp3+ Treg, but not Breg, responses, (2) inhibit autoreactive Th17 and Th1 responses, and (3) effectively ameliorate ongoing disease. These observations demonstrate the potential of BBB-permeable GABAA-R agonists as a new class of treatment to enhance CD8+ and CD4+ Treg responses and limit Th17 and Th1-medaited inflammation in the CNS