Mycophenolate mofetil attenuates uterine ischaemia/reperfusion injury in a rat model.

This study evaluated the effect of mycophenolate mofetil (MMF) on uterine tissue preservation following ischaemia/reperfusion (I/R) injury. Uterine I/R injury was induced in rats by clamping the lower abdominal aorta and ovarian arteries for 30 min. Group I/R + V (n = 7) received vehicle alone while Group I/R + M (n = 7) received 20 mg/kg/day MMF. Control groups underwent sham surgery and received vehicle (Group C) or 20 mg/kg/day MMF (Group M) (n = 7 for both). Four hours after detorsion, uterine tissue 8-hydroxy-2'-deoxyguanosine (8-OHdG), glutathione, malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD) and serum ischaemia modified albumin (IMA) concentrations were measured. Histopathological analyses were performed. The I/R + M group showed significant reduction in serum IMA and uterine tissue 8-OHdG, MDA and MPO and significant increase in SOD concentrations compared with the I/R + V group, indicating a protective effect against I/R oxidative damage (P = 0.009, P = 0.006, P = 0.002, P = 0.003 and P = 0.009, respectively). Histopathological evaluation revealed MMF treatment resulted in significantly less tissue and cellular damage and apoptosis compared with the I/R + V group. These results indicate MMF is effective in attenuating uterine tissue damage and preventing apoptosis following uterine I/R injury, probably via anti-inflammatory and anti-oxidative action.

Feeding During Phases of Altered Mitochondrial Activity: A Theory.

Decisions surrounding the timing and dosing of nutrition support are made for thousands of ICU patients daily and yet remain a topic of controversy. Nutrition support designed to replenish resting energy expenditure (REE) early in critical illness has led to worse clinical outcomes in at least three recent prospective randomized clinical trials. Producing sufficient energy from nutrient substrates requires use of the mitochondrial electron transport chain (ETC). This process is functionally linked to the creation of a tightly regulated series of chemical messengers known as reactive oxygen species (ROS). In health, ROS are kept at low levels by a system of mitochondrial/cellular enzymes and antioxidants, allowing ROS to act as a signal for the redox health of the cell. In inflammatory conditions, however, this system is altered, leading to changes in the physiologic function of the ETC such that its usage produces greater ROS per unit of substrate. This increased ROS is capable of deactivating antioxidant systems, as well as activating further ROS-producing pathways and stimulating localized inflammatory activity. We propose that exacerbation of this process at this time by the forced influx of exogenously acquired nutrient substrates leads to mitochondrial damage, amplified ROS production, increased inflammation, decreased ATP-productive capacity, and, eventually, the death of the cell by either apoptosis or necrosis. Knowledge of this process is vital to determining the safe dosing and timing of nutrition support in the ICU. It is possible that the physiologic cost of meeting the REE under these conditions of mitochondrial stress may simply be too high. This paper details the proposed process by which inappropriately timed feeding in critically ill patients may damage the very mitochondria required for its utilization.