Mangiferin ameliorates collateral neuropathy in tBHP induced nephropathy by inflammation and stress mediated kidney to brain crosstalk

Kidney and brain share common similarities (in anatomy and vaso-regulation) and exhibit clinical interactions in various diseases. To investigate this probable mechanism of kidney to brain crosstalk, we developed an in vivo model of renal injury in mice through intoxication with the oxidative stress inducer, tBHP. Proteinuria, abnormalities in the renal tubules and KIM1 activation was found in tBHP intoxicated animals. Due to this renal pathophysiology, various cytokines from the kidney entered in the brain, triggering the cerebral inflammatory cascades, leading to behavioral anomalies, BBB disruption and brain morphological alterations. Here we introduced mangiferin as a protective molecule owing to its anti-inflammatory and antioxidant property. Mangiferin, via inhibition of apoptosis and activation of the PI3K/Akt pathway protected the kidney. It restored the deleterious phenomena in the damaged brain by downregulating the JNK and p38MAPK mediated pro-apoptotic cascade and activating the intracellular antioxidant thioredoxin, thereby protecting against tBHP induced nephropathy mediated neuropathophysiology.