EFFECTS OF AN ORALLY-ADMINISTERED MISTLETOE (TYPE-2 RIP) LECTIN ON GROWTH, BODY-COMPOSITION, SMALL-INTESTINAL STRUCTURE, AND INSULIN LEVELSIN YOUNG-RATS

The high parenteral al toxicity of mistletoe lectin ML-1, a type-2 RIP (ribosome inactivating protein), with LD50 values of 5 to 10 mu g/kg BW, seriously limits its use as a cytotoxic agent in cancer therapy. A s RIP proteins are generally better tolerated when given orally, we in vestigated the effects of ML-I on growth, gut and body metabolism and composition by feeding rats diets containing 67 or 200 mg ML-1 kg(-1) BW for 10 days. Although ML-I depressed voluntary feed intake and redu ced growth rate, none of the rats lost weight during the experiment. M L-1 had no effect on the digestibility of proteins and other component s of the diet but because of increased urinary nitrogen losses, the ov erall N balance and total body N content were reduced particularly at the higher dose of ML-1. Body fat was also reduced probably due to the depression of circulating insulin levels. Some organs were affected b y oral ML-I: there was hypertrophy of the pancreas and lungs and, most importantly, a dramatic dose-dependent hyperplastic growth of the sma ll intestine, probably due to the avid binding and endocytosis of ML-I by gut epithelial cells. The plasma level of tumour necrosis factor-a lpha was significantly increased by oral ML-1 and there was a similar, though not significant, rise in Interleukin-1 beta levels. These simi larities in cytokine release by oral and intraperitoneal ML-1 suggest that the oral route may be as effective in tumor suppression as the pa renteral. As orally given ML-I was well tolerated by rats with an exte nded nontoxic dose range over that of parenteral parenteral ML-1, the possible advantages in therapy offered by this route could now be prof itably explored. (C) Elsevier Science Inc. 1998.