High-Intensity Interval Training Enhances the Positive Effect of Pentoxifylline on Lipid Profile and Inflammatory Markers in an Endometriosis Animal Model

Abstract

Background: The relationship between endometriosis and cardiovascular disease (CVD) is well established. However, the effects of various exercise training modalities and the anti-inflammatory effects of pentoxifylline (PTX) remain inadequately understood. This investigation is aimed at evaluating the effects of PTX, both independently and in conjunction with high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), on lipid and inflammatory markers including triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and C-reactive protein (CRP) in a rat model of endometriosis. Materials and Methods: Sprague-Dawley's rats were divided into two primary groups: the healthy control group that received no intervention and the induced endometriosis group. Endometriosis was surgically induced in rats, and those with confirmed endometriotic lesions were further categorized into six groups: control, MICT, drug of PTX (D), MICT+D, HIIT, and HIIT+D. Two weeks after laparotomy, PTX consumption and exercise training were performed for 8 weeks. PTX was administered orally at 100 mg/kg/day. MICT and HIIT sessions were conducted 5 days per week, with MICT beginning at 55% of maximum capacity for 31 min in the first week and progressing to 70% of maximum capacity for 46 min by the eighth week. HIIT sessions consisted of 2 min of running followed by 1 min of passive rest at 85% of maximum capacity, starting with seven intervals in the first week and increasing to twelve by the end of the eighth week. The macroscopic size of endometriosis lesions was measured, and cardiovascular risk factors, including hs-CRP, TC, TG, HDL-C, and LDL-C, were assessed in serum samples. Results: The induction of endometriosis was associated with elevated cardiovascular risk factors, including hs-CRP, TC, and TG. HIIT+D significantly decreased lesion volume (p < 0.0001, 95%confidence interval (CI) = 57.239-94.718), hs-CRP (p = 0.049, CI = -54.083 to - 29.478), TC (p = 0.045, CI = -38.607 to - 25.392), and TG (p = 0.042, CI = 25.531-55.801). PTX significantly decreased lesion volume (p < 0.0001, CI =34.709-73.919) and TC (p = 0.016, CI = -45.153 to - 30.179). Conclusion: All interventions except MICT reduced lesion volume, whereas only HIIT+PTX and PTX, in the order of importance, improved some cardiovascular risk indices in the rat model of endometriosis.

Keywords: endometriosis; high-intensity interval training; inflammation; lipid profile; pentoxifylline.

Figure 1

Comparison of TC, TG, HDL-C, LDL-C, and CRP between groups. (a) Comparison of TC (total cholesterol), (b) comparison of TG (triacylglycerols), (c) comparison of HDL-C (high-density lipoprotein cholesterol), (d) comparison of LDL-C (low-density lipoprotein cholesterol), (e) comparison of LDL-C/HDL-C ratio, and (f) comparison of hs-CRP (high-sensitivity C-reactive protein) in serum levels in different groups. HC, healthy control; MICT, moderate-intensity continuous training; D, drug (pentoxifylline); MICT+D, moderate-intensity continuous training+drug (pentoxifylline); HIIT, high-intensity interval training; HIIT+D, high-intensity interval training+drug (pentoxifylline). ⁣^∗p < 0.05: significant difference compared to the control group. Data are presented as mean ± SD.