Bovine lactoferrin decreases histopathological changes in the liver and regulates cytokine production by splenocytes of obstructive jaundiced rats.

Abstract

The aim of this study was to evaluate effects of bovine lactoferrin (BLF) on histopathological changes in the liver of 14 day obstructive jaundiced (OJ) rats and production of tumor necrosis factor (TNF-alpha) and interleukin 6 (IL-6) by splenocytes from 7- and 14-day OJ rats. In the study 50 male rats of the Buffalo strain (170-270 g, mean 230 g) were used. Rats were given 10 mg BLF in 0.5 ml saline daily, using a stomach tube. BLF was applied 2 days before operation and for 13 days following operation. The specimens of liver were prepared using standard techniques. Sections, 5 mm thick were stained with hematoxylin and eosin and reviewed histologically. Microscopic estimation using semiquantitive 4-grade scale was used for evaluation of liver changes. For cytokine measurement splenocyte cultures were stimulated with 5 microg/ml lipopolysaccharide (LPS). After overnight incubation the activities of TNFalpha and IL-6 were determined using bioassays. For statistical evaluation of data the nonparametric Mann-Whitney test was applied. In rats with 14-day OJ, treated with BLF, the pathological changes in the liver were markedly reduced, in particular foci of necrosis with disseminated lymphocytes, cellular necrobiosis, bile duct proliferation and dilation. Neither proliferation of fibrous and reticular connective tissue nor activation of Kupffer cells was revealed. In the 7-day OJ rats treatment with BLF caused significant inhibition of both spontaneous (mean 253, median 275, vs mean 160, median 148 pg/ml, p=0.002) and LPS-induced TNF-alpha production (mean 4967, median 4102, vs mean 2291, median 2234 pg/ ml, p = 0.004) in the splenocyte cultures. The spontaneous (mean 120, median 81, vs mean 43, median 26 pg/ml, p=0.005) as well as LPS-induced IL-6 production (mean 422, median 378, vs mean 293, median 230 pg/ml, p = 0.025) were also lowered. On the other hand, in 14-day OJ, BLF upregulated cytokine production, in particular spontaneous (mean 148, median 158, vs mean 338, median 196, p = 0.001) and LPS-induced TNF-alpha (m ean 1331, median 1507, vs mean 2239, median 1707 pg/ml, p = 0.027). We conclude that oral administration of BLF is beneficial in alleviating deleterious effects of OJ.