233 Metformin Increases Mitochondrial Coupling and Enhances Antioxidant Activity in the Kidneys of Aged Mice Following Thermal Trauma
Bibliographic record
Abstract
Following thermal trauma, a systemic increase in pro-inflammatory mediators and hyperglycemia may culminate in multiple organ dysfunction, sepsis, and ultimately, death. This is particularly true in the elderly population, who are prone to organ failure and adverse outcomes following burn injury. We have recently demonstrated that in patients, metformin administration is equal to insulin in its ability to limit stress-induced hyperglycemia, yet the effects of this agent at the organ and cellular levels have not been thoroughly explored. As acute kidney injury (AKI) and kidney dysfunction are linked to high mortality after traumatic events, we investigated metformin’s benefits on these organs following burn injury in a murine model. Both 8 week (adult) and 50 week (aged) old C57BL/6 mice received a 30% total body surface area dorsal (98°C for 10 sec) and ventral (98°C for 2 sec) scald burn. Select mice received daily intraperitoneal injections post-burn of metformin (100 mg/kg) and kidneys were collected on day 7 post-trauma. Using a Seahorse XF96 extracellular flux analyzer and in-gel activity assays, metformin’s effects on kidney bioenergetics were probed. Changes in levels of oxidized proteins, lipids and nitrosylated proteins were monitored, as well as the activity of the antioxidant enzymes MnSOD, glutathione peroxidase and catalase. Serum creatinine levels were analyzed to assess kidney dysfunction. While kidney damage and dysfunction was not observed in the adult group, the aged cohort demonstrated increased oxidative damage and uncoupling following burn trauma. A 7 day regimen of metformin in these mice lowered oxidative damage and mitochondrial uncoupling while bolstering the activities of antioxidant enzymes. Given the prevalence of mitochondria in the kidneys and the need for aerobic ATP production in this organ, dysfunctional bioenergetics are likely a strong contributing factor to organ failure post-burn. Here, we show that metformin’s effects on mitochondria and antioxidative defense systems may reduce the incidence of kidney dysfunction in the elderly. The data herein demonstrate that metformin treatment in aged animals enhances mitochondrial function and lowers oxidative damage after burn trauma, thus supporting the continued use of this agent in elderly patients.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".