A Combined Phytohemagglutinin And α-Ketoglutarate Pharmacology Study of Gut Morphology and Growth in Older Adult Rats

This study has evaluated the effect of phytohaemagglutinin (PHA) in combination with alpha-ketoglutaric acid (AKG), on GI-tract morphology and N balance in adult rats. Rats, aged approx. 15 months, were assigned to one of four experimental groups, (1) Control group, (2) AKG group, (3) AKG+PHA 100% group and (4) AKG+PHA 1% group. AKG and AKG+PHA were administered via a stomach tube. Rats were treated for a period of 7 days before being killed humanely. Lighter GI-tract weights were found in the AKG and AKG+PHA 1% groups (6.8%, p<0.05 and p<0.01, respectively) compared to that of Control rats, whilst AKG+PHA 100% treatment resulted in no such loss of GI-tract total weight. Interestingly, AKG, AKG+PHA 1% and AKG+PHA 100% treatment resulted in a significant 114% (p<0.05), 116% (p<0.001) and a 145% (p<0.001), increase in duodenal crypt depth, respectively. Moreover, AKG, AKG+PHA 1% and AKG+PHA 100% treatment induced a 107% (p<0.05), 109% (p<0.001) and a 119% (p<0.001), increase in the thickness of the tunica mucosa of the proximal GI-tract, respectively. However, whilst there was a trend towards a reduction in N excretion in urine for the AKG+PHA 100% group, compared to that of the Controls (14.3% lower), this difference was not found to be statistically significant. In conclusion, a combination of PHA and AKG treatment (AKG+PHA 100%) stimulates proliferation of GI-tract crypt depth and tunica mucosa thickness cf. that of Control rats, findings that would be of benefit to the elderly and to individuals suffering from drug induced GI-tract erosion and injury.