Table 2.
Studies With Soy Products and Chemotherapy Toxicities.
| Agents | Toxicities | Treatment | Results | Reference |
|---|---|---|---|---|
| Methotrexate | Gastrointestinal toxicity | 34 SD rats; groups; control group (casein), casein + soy fraction (0.164% of diet) group, casein + soy fraction (0.493% of diet), casein + soy fraction (1.643% of diet) | Improved food intake P < .05, weight gain P < .05, decreasing incidence of diarrhea P < .05 | Funk-Archuleta et al48 |
| Bleomycin | Cytotoxicity and genotoxicity | Human blood lymphocytes obtained from healthy women and human leukemia cell line HL-60 cells (KCLB 10240) pretreated with genistein followed by bleomycin | Enhanced bleomycin-induced cytotoxicity in human leukemia (HL-60) while protecting normal blood lymphocytes | Lee et al12 |
| Cisplatin | Genotoxicity | Human lymphocyte culture of 2 healthy donors treated with cisplatin only and in combination with genistein and gingerol separately in the presence of a metabolic activation system | Reduced genotoxicity because of the free radical scavenging activity of genistein | Beg et al54 |
| Various combination chemotherapy regimens + radiotherapy | Various toxicities | 8 Pediatric patients with cancer (served as their own controls); 9 cycles of chemotherapy without soy isoflavone, 57 cycles of chemotherapy with soy isoflavones; chemotherapy doses and schedules same | Genistein levels were 2 to 6 times higher (range = 0.215-0.411 mg/L; median = 0.258 mg/L) during genistein supplementation compared with the no supplementation period (range = 0.058-0.111 mg/L; median = 0.061 mg/L); genistein supplementation: less myelosuppression (shorter duration of neutropenia), oral mucositis, infections (shorter duration of antibiotic use), blood product requirements; no diarrhea during abdominal radiotherapy | Tacyildiz et al55 |
| Etoposide | Alopecia | 10 SD rats; etoposide injected daily in 11-day-old SD rats at 1.2 mg/kg ip for 3 days, 5 days before the first injection of etoposide, soymetide-4 orally for 8 days concomitantly with indomethacin, AH23848B, pyrilamine, cimetidine, and PDTC | Oral administration soymetide-4: suppression of alopecia induced by etoposide in neonatal rat models | Tsuruki et al81 |
| Methotrexate | Gastrointestinal toxicities | Rats; 5 enteral products containing casein or soy isolate in various forms to 10 rats for 7 days before injection and 7 days after injection of MTX (20 mg/kg) | Soy concentrate diet consumption; maintained food intake above 90% of preinjection levels, which was greater than all other groups at day 3 and those receiving hydrolyzed or intact casein without fiber on day 4 (P < .05), no diarrhea, weight gain when compared with other groups fed hydrolyzed or intact casein without fiber (P < .05), crypt necrosis (in intestine) occurred in all groups except those consuming the soy concentrate diet | Chevreau and Funk-Archuleta50 |
| Methotrexate | Gastrointestinal toxicities | Male SD rats; 5 different experiments; products tested: soybean meal, soybean concentrate, soybean isolate and soybean fiber; 14 days prior to and 7 days following intraperitoneal MTX injection | Soybean meal and soybean concentrate offered the greatest protection, completely alleviating MTX-induced anorexia and diarrhea; soybean concentrate and soybean isolate prevented the necrosis (in the small intestine of MTX-injected animals) observed in animals fed the casein-based semipurified diet | Funk and Baker51 |
| Methotrexate | Gastrointestinal toxicities | Male SD rats; 6 different experiments; products tested: (1) fiber sources, including crystalline cellulose, amorphous cellulose, hemicellulose, and pectin; (2) protein sources, including casein, soybean concentrate, whey isolate, egg albumen, com gluten meal, and hamburger; in experiments 1 to 4, diets for 14 days before MTX injection, experiments 5 and 6 to evaluate time periods prior to or after MTX dosing on toxicity development | Toxicity was lower when 25% of the protein normally supplied by casein was replaced with soybean concentrate, and no toxicity symptoms were present when 50% or more of the protein was provided by soybean concentrate | Funk and Baker52 |
| Cisplatin | Nephrotoxicity | Mice; control (n = 10), genistein (10 mg/kg; n = 10), cisplatin (20 mg/kg; n = 10), and cisplatin plus genistein (n = 10) | Genistein; significantly reduced cisplatin-induced renal injury, ameliorated the cisplatin-induced upregulation of ICAM-1 and MCP-1 expression, resulting in decreased infiltration of macrophages into the kidney, significantly reduced cisplatin-induced generation of ROS and NF-×B activation in HK-2 cells, reduced cisplatin-induced apoptosis in kidney through downregulation of p53 induction | Sung et al82 |
Abbreviations: AH23848B, an antagonist of the PGE2 receptor EP4; HK-2, human kidney; HL-60, human leukemia cells; ICAM-1, immunostaining for intercellular adhesion molecule-1; MCP-1, immunostaining for monocyte chemoattractant protein-1; MTX, methotrexate; NF-κB, nuclear factor-κB; PDTC, pyrrolidine dithiocarbamate ammonium; ROS, reactive oxygen species; SD, Sprague-Dawley.