losartan-potassium and Alcoholism

The neurological disorders and neural pathology brought about by chronic alcoholism are difficult to be reversed. Increasing evidence highlights the protective roles of erythropoietin (EPO) in neurodegenerative diseases and injuries of the central nervous system. In the present study, we investigated the therapeutic effects of EPO on the neurological function deficits and neural pathology caused by chronic alcoholism and the regulatory mechanisms. Using the canonical mouse model of chronic alcohol exposure designed to mimic the repeated cycles of heavy abuse typical of chronic alcoholism, it was found that EPO delivered via intranasal route effectively restored the alcohol‑impaired motor cooperation in rotarod and beam walk tests, reversed alcoholic cognitive and emotional alterations in the novel location recognition task and open‑filed test, and rescued alcohol‑disrupted nervous conduction in the somatosensory‑evoked potential (SSEP) test. Consistently, the intranasally administered EPO promoted the remyelination and synapse formation in chronic alcohol‑affected neocortex and hippocampus as evidenced by immunofluorescence staining and transmission electron microscopy. Additionally, we discovered that the exogenous rhEPO, which entered the cerebrum through intranasal route, activated the erythropoietin receptor (EPOR) and the downstream ERKs and PI3K/AKT signaling, and suppressed autophagy‑related degradation of nuclear factor, erythroid 2‑like 2 (Nrf2). Furthermore, the intranasal EPO‑exerted neuroprotection was almost abolished when the specific Nrf2 antagonist ATRA was administered intraperitoneally prior to intranasal EPO treatment. Collectively, our data demonstrated the repairing potential of EPO for the neurological disorders and neural pathology caused by chronic alcoholism, and identified the Nrf2 activity as the key mechanism mediating the protective effects of EPO.

Topics: Administration, Intranasal; Alcoholism; Animals; Autophagy; Disease Models, Animal; Erythropoietin; Hippocampus; Male; Mice; Mice, Inbred C57BL; Neurodegenerative Diseases; Neuroprotective Agents; NF-E2-Related Factor 2; Phosphatidylinositol 3-Kinases; Receptors, Erythropoietin; Signal Transduction

The erythropoietin levels in mixed cord serum of 40 infants born to drinking women were compared with those of 24 infants born to abstinent women. Twenty infants born to drinkers had signs of fetal alcohol effects. Thirty-five percent of the erythropoietin levels in mixed cord serum of infants of drinking mothers were above the normal range. Further, the elevation in fetal erythropoietin level correlated with maternal alcohol intake; infants of mothers consuming at least 300 g of ethanol weekly (28) had significantly higher (P less than .025) umbilical erythropoietin levels (median 66 mU/mL, range 10-2500) compared with infants of mothers consuming 150-300 g of ethanol weekly (median 37 mU/mL, range 23-215) or infants of control women (median 32 mU/mL, range 11-73). The subgroup analysis between infants with and without fetal alcohol effects showed no differences in umbilical erythropoietin levels. Maternal alcohol ingestion during pregnancy is associated with elevated umbilical erythropoietin levels, but whether this is a direct effect of ethanol or is induced by chronic fetal hypoxemia remains unclear.

Topics: Adult; Alcoholism; Apgar Score; Erythropoietin; Female; Fetal Blood; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications