Early Effects of Hyperbaric Oxygen on Inducible Nitric Oxide Synthase Activity/Expression in Lymphocytes of Type 1 Diabetes Patients: A Prospective Pilot Study

Abstract

This study aimed at examining the early effects of hyperbaric oxygen therapy (HBOT) on inducible nitric oxide synthase (iNOS) activity/expression in lymphocytes of type 1 diabetes mellitus (T1DM) patients. A group of 19 patients (mean age: 63 ± 2.1) with T1DM and with the peripheral arterial disease were included in this study. Patients were exposed to 10 sessions of HBOT in the duration of 1 h to 100% oxygen inhalation at 2.4 ATA. Blood samples were collected for the plasma C-reactive protein (CRP), plasma free fatty acid (FFA), serum nitrite/nitrate, and serum arginase activity measurements. Expression of iNOS and phosphorylation of p65 subunit of nuclear factor-κB (NFκB-p65), extracellular-regulated kinases 1/2 (ERK1/2), and protein kinase B (Akt) were examined in lymphocyte lysates by Western blot. After exposure to HBOT, plasma CRP and FFA were significantly decreased (p < 0.001). Protein expression of iNOS and serum nitrite/nitrate levels were decreased (p < 0.01), while serum arginase activity was increased (p < 0.05) versus before exposure to HBOT. Increased phosphorylation of NFκB-p65 at Ser536 (p < 0.05) and decreased level of NFκB-p65 protein (p < 0.001) in lymphocytes of T1DM patients were observed after HBOT. Decreased phosphorylation of ERK1/2 (p < 0.05) and Akt (p < 0.05) was detected after HBOT. Our results indicate that exposure to HBO decreased iNOS activity/expression via decreasing phosphorylation of ERK1/2 and Akt followed by decreased activity of NFκB.

Effect of Hyperbaric Oxygen Therapy on Fatty Acid Composition and Insulin-like Growth Factor Binding Protein 1 in Adult Type 1 Diabetes Mellitus Patients: A Pilot Study

“…We found that HBOT significantly decreased the plasma level of a specific n-6 PUFA, LA. Considering that increased LA can alter the function of proteins, increase the production of reactive oxidative spaces (48) and stimulate the transcription of NF-kB (49), and also considering our current and previous results (26), we suggest that HBOT modifies signalling pathways and transcription factors involved in the inflammatory response by changing the FA composition in T1DM patients. Changes in FA composition caused by HBOT may be partially responsible for the beneficial effects of HBOT on the vascular function of T1DM patients.…”

“…Because we observed an increased conversion of ALA to DPA and DHA in plasma after HBOT, it would be of interest for our future work to explore the synergistic effect of treatment with n-3 PUFA supplementation and HBOT. Furthermore, in our previous study (26), we observed that the level of CRP was reduced after HBOT in T1DM patients. In the current study, we observed a significant correlation between CRP and DHA level in T1DM patients after HBOT.…”

“…However, HBOT decreased the level of LA (p<0.01) in the plasma of T1DM patients ( Table 2). In previous work, we found that CRP decreased after exposure to HBOT in T1DM patients (26). To evaluate the relationship between CRP and FA composition, we performed linear relationship analysis ( Table 2).…”

“…Grimble et al reported a link between altered FA composition and inflammation in lymphocytes (40). Results from our previous study (26) suggest that the anti-inflammatory effects of HBOT may be linked to the reduction in nuclear factor kappaB (NF-kB) and, consequently, to the reduction of activity and expression of inducible nitric oxide synthase in T1DM patients, so we aimed to evaluate whether HBOT exerts an additional anti-inflammatory effect by changing the FA composition. The literature data show that T1DM patients have increased SFA levels in the plasma (38).…”

Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2–3 trial

“…78 HBOT decrease iNOS activity in patients with diabetic ulcers via phosphorylation of NF-κB subunit p65. 79 However, several sessions of HBOT culminate in increased levels of nitric oxide in diabetic wounds, which is believed to be an important mediator of the effect of the treatment. 80 Although the production of nitric oxide is not directly dependent on the availability of oxygen, it is tightly regulated via feedback loops, and supranormal partial pressures of oxygen induce nitric oxidedependent pathways involved in angiogenesis.…”