Leucine induces cardioprotection in vitro by promoting mitochondrial function via mTOR and Opa-1 signaling.

BACKGROUND AND AIMS: Coronary heart disease is a major global health concern. Further, severity of this condition is greatly influenced by myocardial ischemia/reperfusion (I/R) injury. Branched-chain amino acids (BCAAs) have cardioprotective effects against I/R via mammalian target of rapamycin (mTOR) activity, wherein Leu is considered to particularly regulate mTOR activation. However, the mechanism underlying cardioprotective effects of Leu via mTOR activity is not fully elucidated. Here, we aimed to study the signaling pathway of cardioprotection and mitochondrial function induced by Leu treatment. METHODS AND RESULTS: Cardiac myocytes isolated from adult male Wistar rats were incubated and exposed to simulated I/R (SI/R) injury by replacing the air content. Cardiac myocytes were treated with Leu and subsequently, their survival rate was calculated. To elucidate the signaling pathway and mitochondrial function, immunoblots and mitochondrial permeability transition pore were examined. Cell survival rate was decreased with SI/R but improved by 160 µM Leu (38.5 ± 3.6% vs. 64.5 ± 4.2%, respectively, p < 0.001). Although rapamycin (mTOR inhibitor) prevented this cardioprotective effect induced by Leu, wortmannin (PI3K inhibitor) did not interfere with this effect. In addition, we indicated that overexpression of Opa-1 and mitochondrial function are ameliorated via Leu-induced mitochondrial biogenesis. In contrast, knockdown of Opa-1 suppressed Leu-induced cardioprotection. CONCLUSION: Leu treatment is critical in rendering a cardioprotective effect exhibited by BCAAs via mTOR signaling. Furthermore, Leu improved mitochondrial function.

Predisposing factors and clinical impact of high-output syndrome after sphincter-preserving surgery with covering ileostomy for rectal cancer: a retrospective single-center cohort study.

BACKGROUND: Ileostomy-related high-output syndrome has become a major cause of postoperative morbidity after rectal cancer surgery. This study aimed to clarify the predisposing factors and clinical impact of high-output syndrome. METHODS: Clinical parameters that were associated with high-output syndrome and clinical impact of high-output syndrome on nutritional status, electrolyte abnormality and renal dysfunction were retrospectively investigated in consecutive patients with rectal cancer undergoing resection with covering ileostomy during 2016-2017. RESULTS: High-output syndrome developed in 44/195 eligible patients (22.6%). Multivariable analysis revealed that neoadjuvant (chemo)radiotherapy [odds ratio (OR): 2.4; 95% confidence interval (CI) 1.1-5.2; P = 0.02], postoperative complications (OR: 2.2; 95% CI 1.0-4.6; P = 0.049), postoperative maximal white blood cell ≥ 10,000 cells/µl (OR: 4.0; 95% CI 1.9-8.8; P = 0.0004), and postoperative maximal C-reactive protein ≥ 10 mg/dl (OR: 2.4; 95% CI 1.1-5.2; P = 0.02) were independently associated with high-output syndrome. High-output syndrome was associated with increased renal dysfunction at the time of ostomy closure (29.6% versus 11.9%, patients with high-output syndrome vs. without high-output syndrome, P = 0.008), but not with nutritional imbalance or electrolyte abnormalities. High-output syndrome (OR: 2.5; 95% CI 1.1-5.9; P = 0.03) and postoperative maximal C-reactive protein ≥ 10 mg/dl (OR: 2.4; 95% CI 1.0-5.6; P = 0.04) were independently associated with renal dysfunction at ostomy closure. CONCLUSION: Preoperative (chemo)radiotherapy, postoperative inflammatory response, and postoperative complications predisposed to high-output syndrome, and it significantly impacted postoperative renal dysfunction. Active monitoring and early intervention are warranted to prevent renal dysfunction in patients with these factors.