The effect of theophylline on oxidative stress in serum and tissues in mechanical ventilation-induced diaphragm dysfunction

Introduction: The role of oxidative stress in mechanical ventilation induced diaphragm dysfunction (VIDD) was shown in various studies. In this animal model, we planned to evaluate the role of diaphragmatic and systemic stress on VIDD and the effect of theophylline application on the oxidative stress. Material and methods: Thirty healthy male Sprague-Dawley rats were used. They were evenly divided into 3 groups as Group 1, control group (no application); group 2, placebo group receiving mechanical ventilation (MV); Group 3, theophylline group receiving both MV and theophylline. Malondialdehyde (MDA) and nitric oxide (NO) levels with xanthine oxidase (XO) and superoxide dismutase (SOD) activities were measured in all groups to evaluate the oxidative stress at diaphragm, lung tissue and plasma. Results: SOD (0.01-0.07 U/mg) and XO (0.61-1.76 U/g) activities with NO (0.05-0.14 mu mol/g) levels at diaphragm; XO (0.36-2.26 U/g) activity at lungs and SOD (2.06-5.24 U/mL) and XO (7.76-14.04 U/mL) activities with MDA (0.35-1.09 nmol/L) levels at plasma were significantly increased in placebo group (p < 0.05) compared to control. Upon theophylline therapy, SOD (0.096 U/mg) activity at diaphragm and plasma NO (22.3-29.7 mu mol/L) levels were significantly increased (p < 0.05); whereas XO (0.39 U/g) activity at lungs and plasma MDA (0.36 nmol/L) levels were significantly decreased (p < 0.001) compared to placebo group. Conclusion: In this study, we showed that pulmonary and systemic oxidative stresses accompany MV application induced diaphragmatic oxidative stress in rats and this oxidative stress is predominantly occurs through XO pathway. Also it was demonstrated that theophylline alleviates this oxidative stress by increasing the SOD activity and repressing the XO activity. However, more animal and human studies at molecular level are needed on this subject. Conflict of Interest: Authors have no conflict of interest.