lactoferrin and Stroke

Diabetic hyperglycemia aggravates the prognosis of intracerebral hemorrhagic stroke (ICH) in the clinic. In addition to hematoma expansion and increased inflammation, how diabetic hyperglycemia affects the outcomes of ICH is still unclear. We found that streptozotocin-induced diabetic hyperglycemia not only increased neutrophil infiltration, but also changed the gene expression profile of neutrophils, including lactoferrin (Ltf) encoding gene Ltf. Peroxisome proliferator-activated receptor γ (PPARγ) transcribed Ltf and the lack of neutrophilic Ltf transcription and secretion exacerbated neuronal ferroptosis by accumulating intraneuronal iron. Furthermore, the administration of recombinant Ltf protected against neuronal ferroptosis and improved neurobehavior in hyperglycemic ICH mice, and vice versa. These results indicate that supplementing Ltf or inhibiting neuronal ferroptosis are promising potential strategies to improve the acute outcomes of diabetic ICH in the clinic.

Topics: Animals; Cerebral Hemorrhage; Ferroptosis; Hemorrhagic Stroke; Lactoferrin; Mice; Mice, Obese; Stroke

Whey protein (WH)-enriched diets are reported to aid in weight loss and to improve cardiovascular health. However, the bioactive components in whey responsible for causing such effects remain unidentified.. We determined the effects of whey and its components [α-lactalbumin (LA) and lactoferrin (LF)] on energy balance, glucose tolerance, gut hormones, renal damage, and stroke onset in rats.. Male spontaneously hypertensive stroke-prone (SHRSP) rats (age 8 wk) were fed isocaloric high-fat (40% kcal) and high-salt (4% wt/wt) diets (n = 8-10/group) and randomized for 8 wk to diets enriched as follows: control (CO): 15% kcal from egg albumin, 45% kcal from carbohydrate; WH: 20%kcal WH isolate + 15% kcal egg albumin; LA: 20% kcal LA  + 15% kcal egg albumin; or LF: 20% kcal lactoferrin + 15% kcal egg albumin. Measurements included energy balance (food intake, energy expenditure, and body composition), stroke-related behaviors, brain imaging, glucose tolerance, metabolic hormones, and tissue markers of renal damage. Data were analyzed by linear mixed models with repeated measures or 1-way ANOVA.. Diets enriched with WH, LA, or LF increased survival, with 25% of rats fed these diets exhibiting stroke-associated morbidity, whereas 90% of CO rats were morbid by 8 wk (P < 0.05). The nephritis scores of rats fed WH-, LA-, or LF-enriched diets were 80%, 92%, and 122% lower than those of COs (P = 0.001). The mRNA abundances of renin and osteopontin were 100-600% lower in rats fed WH-, LA-, or LF-enriched diets than in COs (P < 0.05). Urine albumin concentrations and albumin-to-creatinine ratios were 200% lower in rats fed LF-enriched diets than in COs (P < 0.05). Compared with COs, rats fed LF-enriched diets for 2-3 wk had food intake decreased by 29%, body weight decreased by 13-19%, lean mass decreased by 12-19%, and fat mass decreased by 20% (P < 0.001). Relative to COs, rats fed WH and LA had food intake decreased by 10% (P < 0.1), but COs had 12-45% lower weight than rats fed LA- and WH-enriched diets by 3 wk (P < 0.01). Compared with COs, rats fed WH-enriched diets increased energy expenditure by 7%, whereas, rats fed LA-enriched diets had energy expenditure acutely decreased by 7% during the first 4 d, and rats fed LF-enriched diets had energy expenditure decreased by 7-17% throughout the first week ( P < 0.001). Rats fed LA- and LF-enriched diets had blood glucose decreased by 14-19% (P < 0.05) and WH by 9% (P = 0.1), relative to COs. Compared with COs, rats fed LF had GIP decreased by 90% and PYY by 87% (P < 0.05).. Together, these findings indicate that whey and its components α-lactalbumin and lactoferrin improved energy balance and glycemic control, and protected against the onset of neurological deficits associated with stroke and renal damage in male SHRSP rats.

Topics: Animals; Behavior, Animal; Blood Glucose; Brain; Diet; Diet, High-Fat; Eating; Energy Metabolism; Kidney Diseases; Lactalbumin; Lactoferrin; Male; Motor Activity; Rats; Rats, Inbred SHR; Sodium Chloride, Dietary; Stroke; Whey Proteins

The traditional lipid risk factors can only predict some of the cardiovascular events. Our work has focused on new potential biological markers of risk, namely leukocyte activation and erythrocyte membrane damage, in ischemic stroke cases.. Besides the traditional lipid profile, we evaluated the plasma levels of elastase and lactoferrin as markers of leukocyte activation, and membrane band 3 protein profile and membrane bound hemoglobin as markers of erythrocyte damage. Total and differential leukocyte counts and erythrocyte counts, hematocrit and hemoglobin concentrations were also evaluated. The lipid study included the evaluation of triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), apolipoprotein AI (Apo AI) and B (Apo B), and lipoprotein (a) (Lp(a)). The work was performed in a control group (n=29) with no history of cardiovascular events, presenting normal hematological and lipid values, and in a pathologic group (n=21) of ischemic stroke cases diagnosed by computed tomographic imaging.. We found that ischemic stroke was associated with significantly higher values of leukocytes, which seem to be activated, as shown by significant higher levels of elastase and lactoferrin. This activation seems to impose erythrocyte damage, as suggested by a significant increase in membrane bound hemoglobin and by a different band 3 profile.. Our data suggest that plasma levels of elastase and lactoferrin, together with levels of erythrocyte membrane bound hemoglobin and band 3 profile, could be used as powerful new markers of risk for cardiovascular events.

Topics: Adult; Aged; Anion Exchange Protein 1, Erythrocyte; Biomarkers; Brain Ischemia; Erythrocyte Count; Erythrocyte Membrane; Erythrocytes; Hemoglobins; Humans; Lactoferrin; Leukocytes; Lipids; Middle Aged; Pancreatic Elastase; Sensitivity and Specificity; Serologic Tests; Stroke