Protective outcomes of low-dose doxycycline on renal function of Wistar rats subjected to acute ischemia/reperfusion injury

Abstract

Renal ischemia-reperfusion injury (IRI) is a major cause of acute renal failure. Doxycycline (Dc) belongs to the tetracycline-class of antibiotics with demonstrated beneficial molecular effects in the brain and heart, mainly through matrix metalloproteinases inhibition (MMP). However, Dc protection of renal function has not been demonstrated. We determined whether low doses of Dc would prevent decreases in glomerular filtration rate (GFR) and maintain tubular Na handling in Wistar rats subjected to kidney I/R. Male Wistar rats underwent bilateral kidney ischemia for 30min followed by 24h reperfusion (I/R). Doxycycline (1, 3, and 10mg/kg, i.p.) was administered 2h before surgery. Untreated I/R rats showed a 250% increase in urine volume and proteinuria, a 60% reduction in GFR, accumulation of urea-nitrogen in the blood, and a 60% decrease in the fractional Na excretion due to unbalanced Na transporter activity. Treatment with Dc 3mg/kg maintained control levels of urine volume, proteinuria, GFR, blood urea-nitrogen, fractional Na excretion, and equilibrated Na transporter activities. The Dc protection effects on renal function were associated with kidney structure preservation and prevention of TGFβ and fibronectin deposition. In vitro, total MMP activity was augmented in I/R and inhibited by 25 and 50μM Dc. In vivo, I/R augmented MMP-2 and -9 protein content without changing their activities. Doxycycline treatment downregulated total MMP activity and MMP-2 and -9 protein content. Our results suggest that treatment with low dose Dc protects from IRI, thereby preserving kidney function.

Sulfide (Na2S) and Polysulfide (Na2S2) Interacting with Doxycycline Produce/Scavenge Superoxide and Hydroxyl Radicals and Induce/Inhibit DNA Cleavage

“…OXYT modulates inflammatory response [20] and TETR has an effect on growing bones and teeth [21]. DOXY induces cell death, has an anti-apoptotic function or induces apoptosis, reduces or induces ROS, triggers inflammation, reduces cardiac attack, protects cells or renal function from hypoxia-induced injury, prevents proliferation, reduces tumor growth, and suppresses a process of metastasis in human breast or prostate cancer models (for a review see [22,23,24,25,26,27]). Molecular mechanisms of these tetracyclines’ side effects are not fully understood yet and remain to be examined thoroughly.…”

Acute kidey injury risks during cardiac operations are too numerous to count? Could a single actionable variable be the answer?

“…I welcome further dialog and even more well-designed comparative studies that prove the value of kSO2. Things that may reduce/improve AKI risk after cardiac operations Cytochrome-eicosanoid inhibition and AKI 4 High estimated pulmonary artery systolic pressure to predict acute kidney injury 5 Enteral flavone glycoside reduces cardiac surgery-Associated AKI in rats 6 N-acetyl cysteine to prevent postoperative AKI in preexistingrenal-failure 7 Naturetic peptide is best drug with evidence for prevention of AKI 7 Low-dose doxycycline in rats is protective against AKI 8 Early peritoneal dialysis to prevent AKI in neonates 9 Things that do not work for AKI prevention…”

Angiogenesis and Lymphangiogenesis in Peritoneal Dialysis

“…This is possibly mediated by NF-κB inhibition [154]. In fact, in an ischemic-reperfusion renal rat model, doxycycline showed a prolonged renal function due to its protective anti-inflammatory effect [155].…”