Infusions of Casein Hydrolyzates into the Mammary Gland Disrupt Tight Junction Integrity and Induce Involution in Cows

Abstract

Milk stasis triggers local stimuli, which make the tight junctions leak and trigger involution. The aim of the study was to test the hypothesis that casein hydrolyzates compromise tight junction integrity and dry-off milk secretion in dairy cows. Six repeated doses of casein hydrolyzates after each milking during 3 d caused drastic changes in mammary secretion and composition, which were associated with irreversible cessation of milk secretion. No such changes were recorded in the control glands that had been treated with nonhydrolyzed casein. Treatment with casein hydrolyzates disturbed tight junction integrity within 8 h (as indicated by changes in Na+ and K+ concentrations), reduced the concentrations of lactose precipitously, activated the plasmin activator-plasminogen-plasmin system, and induced the secretion of immunoglobulin type G and lactoferrin. At the end of the 3-d treatments, we stopped milking the experimental and control glands. Milk composition 19 d later was similar in the experimental and control glands and was consistent with the composition expected in fully involuted glands. We conclude that casein hydrolyzates are among the milk-borne factors that cause the disruption of tight junction integrity and induce involution in cows. The process induced by casein hydrolyzate was more rapid and synchronized than the involution induced at drying-off.

Lipopolysaccharide challenge of the mammary gland in cows induces nitrosative stress that impairs milk oxidative stability

“…The results of this study were analyzed using repeatedmeasures analysis modeling correlated residuals within cow (SAS Institute, 1990) as described before (Shamay et al, 2003). Briefly, the analysis considered the effects of treatment, day and treatment-day interactions.…”

Induced Physical Distension of Rat Mammary Glands Accelerates the Onset of Apoptosis and Involution

“…Similarly, when milk stored in the mammary gland was diluted with an isosmotic sucrose solution, the milk secretion rate increased suggesting that dilution of a chemical inhibitor occurred [9]. Casein phosphopeptides derived from activation of the milk protease plasmin disrupt TJ and inhibit milk secretion during extended periods of milk accumulation in goats and cows [10,11,61], although the exact mechanism by which this occurs remains to be determined.…”

“…Studies indicate that the increased milk production response to more frequent milk removal was due to removal of a chemical inhibitor in milk of lactating goats [8,9] or casein-derived phosphopeptides causing local disruption of tight junction (TJ) integrity and inhibition of milk secretion in goats and cows [10,11]. The local synthesis of serotonin has also been implicated to disrupt TJ and regulate mammary function in cows [12,13].…”

PA-PG-PL System in Dairy Animals and its Significance: A Review

“…On the other hand, massive activation of the plasmin activity (X150%) is associated with extensive degradation of casein, an inflammatory response (increase in leukocytes and NAGase activity), reduction in lactose concentration and disruption of tight junctions. As a result, fluid, fat and protein secretion are negatively affected, as seen in the response to treatment with CNH of goats (Shamay et al, 2002) and cows (Shamay et al, 2003).…”