Exercise training enhances in vivo clearance of endotoxin and attenuates inflammatory responses by potentiating Kupffer cell phagocytosis

The failure of Kupffer cells (KCs) to remove endotoxin is an important factor in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In this study, the effects of exercise training on KC function were studied in terms of in vivo endotoxin clearance and inflammatory responses. Mice were allocated into rest and exercise groups. KC bead phagocytic capacity and plasma steroid hormone levels were determined following exercise training. Endotoxin and inflammatory cytokine levels in plasma were determined over time following endotoxin injection. KC bead phagocytic capacity was potentiated and clearance of exogenously-injected endotoxin was increased in the exercise group. Inflammatory cytokine (TNF-α and IL-6) levels were lower in the exercise group. We found that only DHEA was increased in the plasma of the exercise group. In an in vitro experiment, the addition of DHEA to RAW264.7 cells increased bead phagocytic capacity and attenuated endotoxin-induced inflammatory responses. These results suggest that exercise training modulates in vivo endotoxin clearance and inflammatory responses in association with increased DHEA production. These exercise-induced changes in KC capacity may contribute to a slowing of disease progression in NAFLD patients

Nuclear factor (erythroid derived 2)-like 2 activation increases exercise endurance capacity via redox modulation in skeletal muscles

Sulforaphane (SFN) plays an important role in preventing oxidative stress by activating the nuclear factor (erythroid derived 2)-like 2 (Nrf2) signalling pathway. SFN may improve exercise endurance capacity by counteracting oxidative stress-induced damage during exercise. We assessed running ability based on an exhaustive treadmill test (progressive-continuous all-out) and examined the expression of markers for oxidative stress and muscle damage. Twelve- to 13-week-old Male wild-type mice (Nrf2+/+) and Nrf2-null mice (Nrf2−/−) on C57BL/6J background were intraperitoneally injected with SFN or vehicle prior to the test. The running distance of SFN-injected Nrf2+/+ mice was significantly greater compared with that of uninjected mice. Enhanced running capacity was accompanied by upregulation of Nrf2 signalling and downstream genes. Marker of oxidative stress in SFN-injected Nrf2+/+ mice were lower than those in uninjected mice following the test. SFN produced greater protection against muscle damage during exhaustive exercise conditions in Nrf2+/+ mice than in Nrf2−/− mice. SFN-induced Nrf2 upregulation, and its antioxidative effects, might play critical roles in attenuating muscle fatigue via reduction of oxidative stress caused by exhaustive exercise. This in turn leads to enhanced exercise endurance capacity. These results provide new insights into SFN-induced upregulation of Nrf2 and its role in improving exercise performance

Severe hypoglycemia during pneumocystis pneumonia treatment associated with trimethoprim–sulfamethoxazole use in a patient on peritoneal dialysis

Abstract Background Trimethoprim–sulfamethoxazole (TMP/SMX) is an essential antimicrobial agent for treating pneumocystis pneumonia (PCP). Furthermore, the risk of hypoglycemia is increased with the co-administration of sulfonylurea due to the presence of the same sulfanilamide structural group in SMX and sulfonylurea. However, hypoglycemia caused by a single administration of TMP/SMX is a rare adverse reaction, and not many cases have been reported. Renal failure is a risk factor for hypoglycemia with single TMP/SMX administration. Case presentation A 54-year-old Japanese woman on peritoneal dialysis (PD) for 10 years was admitted to our hospital for the suspicion of PCP. She underwent immunosuppressive treatment with oral prednisolone (3 mg/day) and a subcutaneous injection of adalimumab (40 mg) every 2 weeks for rheumatoid arthritis. We initiated the administration of a low-to-moderate dose of TMP/SMX (TMP equivalent to TMP/SMX, approximately 8 mg/kg/day) in the patient, considering that she was on PD. At 10 days after administration, the patient became unconscious, and blood test results showed that her blood glucose level was low (15 mg/dL). Unlike hypoglycemia, her serum insulin levels were abnormally high (69.4 μU/mL) at that time. Glucose injection was used for correcting the hypoglycemia, but it was refractory. Highly concentrated glucose infusion was needed to maintain her blood glucose level normal. Her serum insulin level was confirmed to have returned to normal (4.0 μU/mL) at 9 days after completing the TMP/SMX treatment. Conclusions We suspected that the refractory hypoglycemia in this case was caused by high levels of insulin secretion due to the accumulation of TMP/SMX. One of the risk factors in this patient was the low excretion rate of TMP/SMX into the PD fluid. Although hypoglycemia is a rare complication of TMP/SMX, we should consider this risk during TMP/SMX use in patients, especially those on PD