platonin and Reperfusion-Injury

Studies have found that Platonin has neuroprotective effect, but its molecular mechanism needs further study. We found that at the early stage of cerebral ischemia/reperfusion injury, Platonin treatment significantly reduced cerebral infarct lesions, improved neurological scores, and exerted neuroprotective effects. Our group has shown that NLRP3 inflammasomes activation is required to mediate neuronal injury during cerebral ischemia /reperfusion injury. The brain protective effect of Platonin is related to its ability to effectively regulate autophagy and NLRP3 inflammasomes-derived inflammation. Platonin treatment effectively induced autophagy (LC3II/I, p62) and reduced NLRP3 inflammasomes activation(NLRP3, cleaved-IL-1β，cleaved-IL-18, cleaved-caspase1). However, 3-MA (15 mg/kg) treatment downregulated the inhibitory effect of Platonin on NLRP3 inflammasomes. We also studied the location of BNIP3 in Platonin-mediated neuroprotection and found that Platonin induced the expression of autophagic protein BNIP3 and enhanced the co-immunoprecipitation of BNIP3 with LC3, and double-labeled immunofluorescence also showed enhanced co-localization of BNIP3 with LC3. Finally, si-BNIP3 transfection attenuated the co localization of BNIP3 with LC3, decreased the autophagy activity to a certain extent and blocked the inhibition of NLRP3 inflammasomes-derived inflammation by Platonin. This study demonstrated that Platonin may play a neuroprotection role in cerebral I / R injury by inhibiting NLRP3 inflammasomes activation through upregulating autophagy via BNIP3 / LC3 pathway.

Topics: Animals; Autophagy; Disease Models, Animal; Inflammasomes; Membrane Proteins; Microtubule-Associated Proteins; Mitochondrial Proteins; Neuroprotective Agents; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Reperfusion Injury; Thiazoles

Bilateral lower limb ischemia-reperfusion (I/R) could cause significant oxidative stress, elicit inflammatory response, and subsequently induce kidney injury in animals. We tested the effects of platonin, a potent antioxidant, on mitigating the kidney injury induced by lower limb I/R in rats.. Adult male rats were allocated to receive I/R or I/R plus platonin (100 μg/kg intravenous injection immediately after reperfusion), and denoted as the I/R or the I/R-P group, respectively (n = 10 in each group). Sham groups were run simultaneously. Bilateral lower limb I/R was achieved by applying rubber-band tourniquets high around each thigh for 3 hours, followed by reperfusion for 6 hours. After sacrifice, the level of kidney injury was assayed.. I/R significantly increased the plasma concentrations of blood urea nitrogen (BUN) and creatinine (Cr). However, this effect could be mitigated by platonin, as the plasma concentrations of BUN and Cr of the I/R-P group were significantly lower than those of the I/R group. Moreover, histological findings revealed moderate injury in kidney tissues of the I/R group and mild injury in those of the I/R-P group. In addition, the leukocyte infiltration and myeloperoxidase activity in kidney tissues as well as the renal concentrations of inflammatory molecules (i.e., cyclooxygenase-2/prostaglandin E(2), interleukin-6, and macrophage inflammatory protein-2) and malondialdehyde (i.e., the index of lipid peroxidation) of the I/R group were significantly higher than those of the I/R-P group.. Platonin attenuates kidney injury induced by bilateral lower limb I/R in rats.

Topics: Animals; Blood Pressure; Dinoprostone; Heart Rate; Kidney; Lower Extremity; Male; Peroxidase; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Thiazoles

Oxidative stress and inflammatory response are crucial in mediating the development of acute lung injury induced by bilateral lower limb ischemia-reperfusion (I/R). Platonin, a potent antioxidant, possesses anti-inflammation capacity. We sought to elucidate whether platonin could mitigate acute lung injury induced by lower limb I/R.. Forty-eight adult male rats were allocated to receive I/R, I/R plus platonin (100 μg/kg intravenous injection immediately after reperfusion), sham instrumentation, or sham instrumentation plus platonin (denoted as the I/R, I/R-platonin, Sham, or Sham-platonin group, respectively; n = 12 in each group). Bilateral hind limb I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 3 h. After sacrifice, the degree of lung injury was determined.. Histologic findings revealed moderate inflammation in lung tissues of the I/R group and mild inflammation in those of the I/R-platonin group. Total cell number and protein concentration in bronchoalveolar lavage fluid as well as the leukocyte infiltration and myeloperoxidase activity in lung tissues of the I/R group were significantly higher than those of the I/R-platonin group. The pulmonary concentrations of macrophage inflammatory protein-2, interleukin-6, and prostaglandin E(2) of the I/R group were significantly higher than those of the I/R-platonin group. Moreover, the plasma nitric oxide concentration as well as the nitric oxide and malondialdehyde concentrations in lung tissues of the I/R group were significantly higher than those of the I/R-platonin group.. Platonin mitigates acute lung injury induced by bilateral lower limb I/R in rats.

Topics: Acute Lung Injury; Animals; Antioxidants; Chemokine CXCL2; Dinoprostone; Injections, Intravenous; Interleukin-6; Leukocytes; Lower Extremity; Male; Malondialdehyde; Models, Animal; Nitric Oxide; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Thiazoles