RESPONSES OFF THE RAT'S LIVER AND SERUM GLUTAMATE AND ISOC1TRATE .DEHYDROGENASES AND ORNITHINE CARBOMYL- TRANSFERASE TO A HAEMAGGLUTININ FROM LIMA BEAN (Phaseolus lunatus Linn.)

The responses of liver and serum gluta­mate dehydrogenase (CDII; EC 1.4.1.2.), isocitrate dehydrogenase (ICDH; EC 1.1. 1.42) and the urea cycle enzyme, ornithine carbamoyltransferase (OCT; EC 2. 1.3.3) to dietary lima bean haemagglutinin (lectin) were assessed using a total of S4 growing rats. The GDH and ICDH activities in the liver were highly significantly (P < 0.001) eleva­ted by dietary haemagglutinin. The activi­ties correlated significantly (P < 0.01) with the haemagglutinin levels in a positive quadratic fashion as judged by their res­pective R2, coefficient of multiple deter­mination of 0.91 and 0.95. Liver OCT activity was significantly (P < 0.05) depresse­ed but correlated poorly with haemagglu­tinin levels. Activities of the serum dehydrogenases were significantly (P < 0.05) altered by dietary haemagglutinin. Although serum OCT activity tended to increase, such increases were however not significant. Serum GDH and ICDH values correlated significantly (P < 01.05) with haemagglutinin levels with respective R2 values of 0.71 and 0.67. The veterinary implication is highlighted and some remedies suggested.

Influence of feeding increasing levels of dry or modified wet corn distillers’ grains plus solubles in whole corn grain-based finishing diets on hepatic and renal mass, and glutathione peroxidase and urea cycle enzyme activities in finishing cattle

Salim, H., Wood, K. M., Cant, J. P. and Swanson, K. C. 2015. Influence of feeding increasing levels of dry or modified wet corn distillers’ grains plus solubles in whole corn grain-based finishing diets on hepatic and renal mass, and glutathione peroxidase and urea cycle enzyme activities in finishing cattle. Can. J. Anim. Sci. 95: 407–415. Forty-two cross-bred steers (BW=357±5.8 kg) fed whole corn grain-based finishing diets were used in a completely randomized block (60, 120, or 180 d on feed) design (2×3 factorial arrangement of treatments plus control) to determine the effect of inclusion level [0 (control), 16.7, 33.3, and 50% of diet DM) and form (dry (DDGS) or modified wet (MWDGS)] of distillers’ grains plus solubles (DGS) on hepatic and renal glutathione peroxidase (GPx) and hepatic urea cycle enzyme activities. Kidney weight (g kg−1of BW) increased linearly (P=0.004) with increasing inclusion levels of DGS. There were no effects (P≥0.11) of dietary treatment on hepatic and renal GPx activity (U g−1, U mg−1of protein, and kU liver−1). Hepatic carbamoyl phosphate synthetase activity (kU liver−1and U kg−1of BW) tended to linearly increase (P=0.09 and P=0.10, respectively) with increasing inclusion level of DGS. Hepatic ornithine transcarbamoylase and argininosuccinate synthetase activity (kU liver−1and U kg−1of BW) increased linearly (P≤0.05) with increasing inclusion levels of DGS. These data indicate that steers adapt to feeding up to 50% DGS by increasing kidney mass and activity of urea cycle enzymes in liver to allow for clearance of excess nitrogen. Also, hepatic and renal GPx activity, as an indicator of Se status, is not affected when typical finishing diets are fed.

Experimental nonalcoholic steatohepatitis compromises ureagenesis, an essential hepatic metabolic function

Nonalcoholic steatohepatitis (NASH) is increasing in prevalence, yet its consequences for liver function are unknown. We studied ureagenesis, an essential metabolic liver function of importance for whole body nitrogen homeostasis, in a rodent model of diet-induced NASH. Rats were fed a high-fat, high-cholesterol diet for 4 and 16 wk, resulting in early and advanced experimental NASH, respectively. We examined the urea cycle enzyme mRNAs in liver tissue, the hepatocyte urea cycle enzyme proteins, and the in vivo capacity of urea-nitrogen synthesis (CUNS). Early NASH decreased all of the urea cycle mRNAs to an average of 60% and the ornithine transcarbamylase protein to 10%, whereas the CUNS remained unchanged. Advanced NASH further decreased the carbamoyl phosphate synthetase protein to 63% and, in addition, decreased the CUNS by 20% [from 5.65 ± 0.23 to 4.58 ± 0.30 μmol × (min × 100 g)−1; P = 0.01]. Early NASH compromised the genes and enzyme proteins involved in ureagenesis, whereas advanced NASH resulted in a functional reduction in the capacity for ureagenesis. The pattern of urea cycle perturbations suggests a prevailing mitochondrial impairment by NASH. The decrease in CUNS has consequences for the ability of the body to adjust to changes in the requirements for nitrogen homeostasis e.g., at stressful events. NASH, thus, in terms of metabolic consequences, is not an innocuous lesion, and the manifestations of the damage seem to be a continuum with increasing disease severity.