Postprandial leucine and insulin responses and toxicological effects of a novel whey protein hydrolysate-based supplement in rats

Table 1 Dose-dependent effects of WPH feeding for 30 days on liver and kidney histopathology markers

Variable	water (n = 5)	low (n = 5)	medium (n = 5)	high (n = 5)
Kidney histopathology
basophilia of tubules in corticomedullary junction	0/5	1/5	0/5	1/5
moderate unilateral hydronephrosis	0/5	0/5	0/5	1/5
large focal tubular regeneration with lymphocytes	0/5	0/5	1/5	0/5
focal tubular mineralization	0/5	1/5	0/5	0/5
focal perivascular lymphoid infiltrate	1/5	0/5	0/5	0/5
1-2 proteinaceous tubular casts	3/5	0/5	0/5	1/5
tubular regeneration with interstitial lymphocytes	1/5	0/5	0/5	1/5
focal tubular regeneration	2/5	0/5	2/5	1/5
Liver histopathology
moderate multifocal centrilobular lipidosis	1/5	3/5	2/5	1/5
mild multifocal centrilobular lipidosis	3/5	2/5	2/5	3/5
few mild foci lipidosis	1/5	0/5	1/5	1/5
1-2 multinucleated giant cells	1/5	1/5	1/5	1/5
focal granulopoeisis	0/5	1/5	0/5	0/5
focal erythropoeisis	3/5	0/5	0/5	1/5
>21 hepatocellular mitoses	4/5^†	0/5	0/5	0/5
11-20 hepatocellular mitoses	0/5	2/5	1/5	0/5
1-10 hepatocellular mitoses	1/5	3/5	4/5	1/5
6-10 apoptotic cells	3/5	0/5	1/5	0/5
1-5 apoptotic cells	2/5	5/5	3/5	3/5
6-10 microgranulomas	2/5	0/5	1/5	0/5
1-5 microgranulomas	3/5	2/5	3/5	3/5

Effects of 30 days of daily gavage feeding 1 human equivalent dose (1.1 g/d, ‘low’), 3 human equivalent doses (3.4 g/d, ‘medium’), and 6 human equivalent doses (6.8 g/d, ‘high’) of the WPH-based supplement as well as water only (‘water’) on markers of kidney and liver damage.
Liver apoptotic cell and microgranuloma counts represent potential liver injury/damage; hepatocellular mitoses and focal granuloposis/erythropoesis counts represent potential liver regeneration after injury; liver lipidosis counts represent the development of fatty liver.
Kidney histopathlogy definitions [derived from reference Guyton and Hall [13]:
Basophilia of tubules in corticomedullary junction counts represent potential nephron damage; moderate unilateral hydronephrosis represent excessive dilation of the kidneys and potential decrement in kidney function; large focal tubular regeneration with lymphocytes counts represent potential kidney damage and toxicity; focal tubular mineralization counts represent potential tubular damage; focal perivascular lymphoid infiltrate counts represent potential kidney damage and toxicity.
Liver histopathology definitions (derived from reference Guyton and Hall [13]):
Symbols: ^† indicates proportion of observations with water is significantly higher than observations in different treatment conditions as determined by a Chi-square test (p = 0.001).

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