In vivo assessment of toxicity and pharmacokinetics of methylglyoxal. Augmentation of the curative effect of methylglyoxal on cancer-bearing mice by ascorbic acid and creatine.
Previous in vivo studies from several laboratories had shown remarkable curative effect of methylglyoxal on cancer-bearing animals. In contrast, most of the recent in vitro studies have assigned a toxic role for methylglyoxal. The present study was initiated with the objective to resolve whether methylglyoxal is truly toxic in vivo and to reassess its therapeutic potential. Four species of animals, both rodent and non-rodent, were treated with different doses of methylglyoxal through oral, subcutaneous and intravenous routes. Acute (treatment for only 1 day) toxicity tests had been done with mouse and rat. These animals received 2, 1 and 0.3 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Chronic (treatment for around a month) toxicity test had been done with mouse, rat, rabbit and dog. Mouse, rat and dog received 1, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Rabbit received 0.55, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. It had been observed that methylglyoxal had no deleterious effect on the physical and behavioral pattern of the treated animals. Fertility and teratogenecity studies were done with rats that were subjected to chronic toxicity tests. It had been observed that these animals produced healthy litters indicating no damage of the reproductive systems as well as no deleterious effect on the offspring. Studies on several biochemical and hematological parameters of methylglyoxal-treated rats and dogs and histological studies of several organs of methylglyoxal-treated mouse were performed. These studies indicated that methylglyoxal had no apparent deleterious effect on some vital organs of these animals. A detailed pharmacokinetic study was done with mouse after oral administration of methylglyoxal. The effect of methylglyoxal alone and in combination with creatine and ascorbic acid on cancer-bearing animals had been investigated by measuring the increase in life span and tumor cell growth inhibition. The results indicated that anticancer effect of methylglyoxal was significantly augmented by ascorbic acid and further augmented by ascorbic acid and creatine. Nearly 80% of the animals treated with methylglyoxal plus ascorbic acid plus creatine were completely cured and devoid of any malignant cells within the peritoneal cavity.
Ghosh
Manju
M
Department of Biological Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata-700 032, India.
Talukdar
Dipa
D
Ghosh
Swapna
S
Bhattacharyya
Nivedita
N
Ray
Manju
M
Ray
Subhankar
S
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000633:toxicity*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000473:pathology; D003401:Creatine / Q000627:therapeutic use*; D004285:Dogs; D004357:Drug Synergism; D004798:Enzymes / Q000097:blood; D005260:Female; D005298:Fertility / Q000187:drug effects; D008136:Longevity / Q000187:drug effects; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D011765:Pyruvaldehyde / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000633:toxicity*; D011817:Rabbits; D051381:Rats; D012098:Reproduction / Q000187:drug effects; D013045:Species Specificity; D016019:Survival Analysis; D013723:Teratogens / Q000633:toxicity; D014815:Vitamins / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D004798:Enzymes; D013723:Teratogens; D014815:Vitamins; D011765:Pyruvaldehyde; D003401:Creatine; D001205:Ascorbic Acid